Debra L. Beck

TORONTO – Efforts to prevent suicide contagion in the community are targeted wrongly, Dr. Robert Michels said at the annual meeting of the American Psychiatric Association. Rather than target those at risk for suicide contagion – those with mental illness – precious resources are used to “soothe” individuals who are not at risk for suicide.

“The suicidality that occurs after a publicly known suicide event is most adequately dealt with in terms of the use of scarce resources – not by providing hotlines and suicide assistance programs – but rather by providing adequate care for the mentally ill in the community,” Dr. Michels said during a session addressing the issue of suicide from different perspectives.

Soothing or prevention?

Most suicides – up to 90% of them – are committed by individuals with preexisting mental illness. But when a prominent suicide occurs in the community, resources are spent largely on soothing the larger population, which has no or minimal risk of suicide.

“We know that if there is a suicide event, the most important thing we can do in preventing true cluster phenomenon is to find those who are at risk and provide them with good treatment for their psychopathology,” said Dr. Michels, the Walsh McDermott University Professor of Medicine at Cornell University in New York, and University Professor of Psychiatry at Weill Medical College at the university. “A common response to suicides is to provide social support and soothing for the general population, a largely worthless process in terms of suicide prevention, and one that some have suggested may even cause some suicides.”

A suicide cluster is defined as multiple suicidal behaviors or suicides that fall within an accelerated time frame, and sometimes within a defined geographic area. Suicide contagion is particularly a concern among adolescents who are often considered the most vulnerable to this phenomenon. Suicide clustering is a matter of some debate, as is the role of the media in it.

“The best treatment to prevent suicide is to treat those mental illnesses that have suicide as a common and expected sequelae of them, not by preventing the suicidal act late in the course of the illness or by blocking out the precipitants that may lead to the event, but rather by treating the underlying predisposing disorder and therefore changing the course of the illness,” Dr. Michels said.

He described the “typical situation,” where there has been a completed suicide in a high school, and mental health professionals go into the school to provide group sessions for all the students “to comfort and soothe them from their pain and distress.” However, the “great majority of those students are not at risk at all,” said Dr. Michels. “They may profit from the soothing, and it may be a humane thing to do, but the students who are at risk are the ones who are heavy substance abusers, who are depressed, or who have some other premorbid condition.”

The preferred response would be to use scarce resources to provide better mental health services to the vulnerable, rather than to soothe the sad. “When an event occurs that makes the vulnerable victims, we soothe the victims’ families and friends but what we ought to do is take those resources and help the vulnerable,” he said.

Educating the public

Publicly known suicides often have an important impact on the general population, which obligates the mental health community to react to them properly and effectively, Dr. Michels said.

“We know the huge role of psychopathology in the cause of suicide,” said Dr. Michels. “We know that depression, psychotic illness, or substance abuse are found in 90% of people who commit suicide, but the public isn’t fully aware of this, and therefore the public embraces the atypical stories of the suicide that grows out of a meaningful life situation in the absence of depression or psychosis or substance abuse.”

It’s up to the mental health community to better educate the public about the strong link between mental illness and suicide, he said.

At the end of the scheduled talks, participants were invited to join in a 45-minute group question-and-answer session that touched on the many ways suicide affects the community, including mental health professionals. In response to comments on the suicide of Robin Williams and on the suicide/murder of the Germanwings copilot, Dr. Michels again called on the mental health profession to lead the way in educating the public.

“I think there is a reasonable concern about misleading the public to think that there is a link between a suicide event and mass murder,” he said. “There is a very thin link in that mass murderers sometimes also kill themselves, but we wouldn’t want to stigmatize further the vast majority of people who kill themselves or try to kill themselves who aren’t murderers, in the same way we have to be careful about the fact that mass murderers are often mentally ill.

“Many in the public have the idea that mental illness is a risk factor for mass murder, which it isn’t, so we have to be careful about how we approach that subject, not to further encourage false beliefs in the public about the corollaries of mental illness.”

Dr. Michels is past president of the American Board of Psychiatry and Neurology, and the American College of Psychiatrists, and is a former member of the Board on Mental Health and Behavioral Medicine of the National Academy of Sciences, Institute of Medicine. He had no disclosures.

TORONTO – Efforts to prevent suicide contagion in the community are targeted wrongly, Dr. Robert Michels said at the annual meeting of the American Psychiatric Association. Rather than target those at risk for suicide contagion – those with mental illness – precious resources are used to “soothe” individuals who are not at risk for suicide.

“The suicidality that occurs after a publicly known suicide event is most adequately dealt with in terms of the use of scarce resources – not by providing hotlines and suicide assistance programs – but rather by providing adequate care for the mentally ill in the community,” Dr. Michels said during a session addressing the issue of suicide from different perspectives.

Soothing or prevention?

Most suicides – up to 90% of them – are committed by individuals with preexisting mental illness. But when a prominent suicide occurs in the community, resources are spent largely on soothing the larger population, which has no or minimal risk of suicide.

“We know that if there is a suicide event, the most important thing we can do in preventing true cluster phenomenon is to find those who are at risk and provide them with good treatment for their psychopathology,” said Dr. Michels, the Walsh McDermott University Professor of Medicine at Cornell University in New York, and University Professor of Psychiatry at Weill Medical College at the university. “A common response to suicides is to provide social support and soothing for the general population, a largely worthless process in terms of suicide prevention, and one that some have suggested may even cause some suicides.”

A suicide cluster is defined as multiple suicidal behaviors or suicides that fall within an accelerated time frame, and sometimes within a defined geographic area. Suicide contagion is particularly a concern among adolescents who are often considered the most vulnerable to this phenomenon. Suicide clustering is a matter of some debate, as is the role of the media in it.

“The best treatment to prevent suicide is to treat those mental illnesses that have suicide as a common and expected sequelae of them, not by preventing the suicidal act late in the course of the illness or by blocking out the precipitants that may lead to the event, but rather by treating the underlying predisposing disorder and therefore changing the course of the illness,” Dr. Michels said.

He described the “typical situation,” where there has been a completed suicide in a high school, and mental health professionals go into the school to provide group sessions for all the students “to comfort and soothe them from their pain and distress.” However, the “great majority of those students are not at risk at all,” said Dr. Michels. “They may profit from the soothing, and it may be a humane thing to do, but the students who are at risk are the ones who are heavy substance abusers, who are depressed, or who have some other premorbid condition.”

The preferred response would be to use scarce resources to provide better mental health services to the vulnerable, rather than to soothe the sad. “When an event occurs that makes the vulnerable victims, we soothe the victims’ families and friends but what we ought to do is take those resources and help the vulnerable,” he said.

Educating the public

Publicly known suicides often have an important impact on the general population, which obligates the mental health community to react to them properly and effectively, Dr. Michels said.

“We know the huge role of psychopathology in the cause of suicide,” said Dr. Michels. “We know that depression, psychotic illness, or substance abuse are found in 90% of people who commit suicide, but the public isn’t fully aware of this, and therefore the public embraces the atypical stories of the suicide that grows out of a meaningful life situation in the absence of depression or psychosis or substance abuse.”

It’s up to the mental health community to better educate the public about the strong link between mental illness and suicide, he said.

At the end of the scheduled talks, participants were invited to join in a 45-minute group question-and-answer session that touched on the many ways suicide affects the community, including mental health professionals. In response to comments on the suicide of Robin Williams and on the suicide/murder of the Germanwings copilot, Dr. Michels again called on the mental health profession to lead the way in educating the public.

“I think there is a reasonable concern about misleading the public to think that there is a link between a suicide event and mass murder,” he said. “There is a very thin link in that mass murderers sometimes also kill themselves, but we wouldn’t want to stigmatize further the vast majority of people who kill themselves or try to kill themselves who aren’t murderers, in the same way we have to be careful about the fact that mass murderers are often mentally ill.

“Many in the public have the idea that mental illness is a risk factor for mass murder, which it isn’t, so we have to be careful about how we approach that subject, not to further encourage false beliefs in the public about the corollaries of mental illness.”

Dr. Michels is past president of the American Board of Psychiatry and Neurology, and the American College of Psychiatrists, and is a former member of the Board on Mental Health and Behavioral Medicine of the National Academy of Sciences, Institute of Medicine. He had no disclosures.

TORONTO – Efforts to prevent suicide contagion in the community are targeted wrongly, Dr. Robert Michels said at the annual meeting of the American Psychiatric Association. Rather than target those at risk for suicide contagion – those with mental illness – precious resources are used to “soothe” individuals who are not at risk for suicide.

“The suicidality that occurs after a publicly known suicide event is most adequately dealt with in terms of the use of scarce resources – not by providing hotlines and suicide assistance programs – but rather by providing adequate care for the mentally ill in the community,” Dr. Michels said during a session addressing the issue of suicide from different perspectives.

Soothing or prevention?

Most suicides – up to 90% of them – are committed by individuals with preexisting mental illness. But when a prominent suicide occurs in the community, resources are spent largely on soothing the larger population, which has no or minimal risk of suicide.

“We know that if there is a suicide event, the most important thing we can do in preventing true cluster phenomenon is to find those who are at risk and provide them with good treatment for their psychopathology,” said Dr. Michels, the Walsh McDermott University Professor of Medicine at Cornell University in New York, and University Professor of Psychiatry at Weill Medical College at the university. “A common response to suicides is to provide social support and soothing for the general population, a largely worthless process in terms of suicide prevention, and one that some have suggested may even cause some suicides.”

A suicide cluster is defined as multiple suicidal behaviors or suicides that fall within an accelerated time frame, and sometimes within a defined geographic area. Suicide contagion is particularly a concern among adolescents who are often considered the most vulnerable to this phenomenon. Suicide clustering is a matter of some debate, as is the role of the media in it.

“The best treatment to prevent suicide is to treat those mental illnesses that have suicide as a common and expected sequelae of them, not by preventing the suicidal act late in the course of the illness or by blocking out the precipitants that may lead to the event, but rather by treating the underlying predisposing disorder and therefore changing the course of the illness,” Dr. Michels said.

He described the “typical situation,” where there has been a completed suicide in a high school, and mental health professionals go into the school to provide group sessions for all the students “to comfort and soothe them from their pain and distress.” However, the “great majority of those students are not at risk at all,” said Dr. Michels. “They may profit from the soothing, and it may be a humane thing to do, but the students who are at risk are the ones who are heavy substance abusers, who are depressed, or who have some other premorbid condition.”

The preferred response would be to use scarce resources to provide better mental health services to the vulnerable, rather than to soothe the sad. “When an event occurs that makes the vulnerable victims, we soothe the victims’ families and friends but what we ought to do is take those resources and help the vulnerable,” he said.

Educating the public

Publicly known suicides often have an important impact on the general population, which obligates the mental health community to react to them properly and effectively, Dr. Michels said.

“We know the huge role of psychopathology in the cause of suicide,” said Dr. Michels. “We know that depression, psychotic illness, or substance abuse are found in 90% of people who commit suicide, but the public isn’t fully aware of this, and therefore the public embraces the atypical stories of the suicide that grows out of a meaningful life situation in the absence of depression or psychosis or substance abuse.”

It’s up to the mental health community to better educate the public about the strong link between mental illness and suicide, he said.

At the end of the scheduled talks, participants were invited to join in a 45-minute group question-and-answer session that touched on the many ways suicide affects the community, including mental health professionals. In response to comments on the suicide of Robin Williams and on the suicide/murder of the Germanwings copilot, Dr. Michels again called on the mental health profession to lead the way in educating the public.

“I think there is a reasonable concern about misleading the public to think that there is a link between a suicide event and mass murder,” he said. “There is a very thin link in that mass murderers sometimes also kill themselves, but we wouldn’t want to stigmatize further the vast majority of people who kill themselves or try to kill themselves who aren’t murderers, in the same way we have to be careful about the fact that mass murderers are often mentally ill.

“Many in the public have the idea that mental illness is a risk factor for mass murder, which it isn’t, so we have to be careful about how we approach that subject, not to further encourage false beliefs in the public about the corollaries of mental illness.”

Dr. Michels is past president of the American Board of Psychiatry and Neurology, and the American College of Psychiatrists, and is a former member of the Board on Mental Health and Behavioral Medicine of the National Academy of Sciences, Institute of Medicine. He had no disclosures.

TORONTO – In patients hospitalized for borderline personality disorder (BPD) and other complex psychiatric disturbances, symptoms of depression and emotional dysregulation continue to progressively improve over several weeks. But at 1 week, the improvement is minimal, which is an issue given that the average psychiatric hospitalization in the United States is only 5 to 7 days.

“So more time [in the hospital] may be something that we have to lobby for,” Dr. John M. Oldham said during a talk at the American Psychiatric Association (APA) annual meeting.

Dr. Oldham showed preliminary results from the Menninger Clinic’s Hospital-Wide Outcomes Project as part of a longer discussion on the current state of personality disorders research. Dr. Oldham is chief of staff and senior vice president at Menninger in Houston. He also is an internationally recognized specialist in personality disorders and a past president of the APA. There is a “fair drumbeat” in the literature and in clinical circles suggesting long hospitalizations should be avoided in BPD patients, because the illness tends to be associated with regression.

“Well, I think that’s good advice, if you can get away with it,” Dr. Oldham said. Unfortunately, some patients will need longer term hospitalization for refractory symptoms, persistent or severe suicidality, self-destructiveness, or nonadherence to treatment, among other indications.

At the Menninger Clinic, all patients are administered structured psychiatric interviews (e.g., the Structured Clinical Interview for DSM-IV Axis I Disorders [SCID-I] and the Structured Clinical Interview for DSM-IV Axis II Disorders [SCID-II] at admission, as well as a battery of self-report tests that provide objective data on clinical symptoms, level of functioning, interpersonal relationships, and treatment progress and process (working relationships with treatment team members and treatment engagement). Symptom and functional assessments are repeated every 2 weeks during hospitalization. Patients are asked to complete a similar battery of self-report measures 2 weeks after discharge and then every 3 months after that for 18 months. More than 1,600 patients have participated in the study since it began in 2008.

“We have an unusual, unique opportunity to do this work, because our average length of stay at the Menninger Clinic for an inpatient is 45 days, which is very unusual in hospital psychiatry these days,” Dr. Oldham said.

“There’s only one way we can do it, and that is that 80% of our patients are self-pay, so [we’re looking at] a layer of a higher socioeconomic bracket because the insurance companies will not pay for longer care.”

The hope of the Menninger investigators is to use their data to make the case that for some patients – and many of the Menninger patients “have not been able to get better with the usual available treatment” – that it’s cost effective to treat these difficult cases for significantly longer periods in hospital.

Progressively reduced symptoms

The Menninger data so far include 255 patients with BPD and 1,129 patients without BPD, and these numbers are steadily increasing. Dr. Oldham explained that the many of the 1,129 non-BDP patients have complex conditions that are generally a mood disorder and an underlying personality disorder and “almost always” a substance abuse issue, too.

In preliminary data shown by Dr. Oldham, the self-administered Patient Health Questionnaire-9 (PHQ-9) depression severity scale is high in both groups on admission, ranking as “severe” in the BPD group and “moderate” in the non-BPD arm.

At 1 week – the length of a usual hospitalization – the BPD patients have dropped to moderate on the scale, and the non-BDP patients to mild, but after 6 weeks, both groups have dropped further on the scale such that the BPD patients have only mild symptoms and the non-BDP patients are approaching normal levels of depressed affect.

“At the 1-week mark … you can see that the patient is a little bit better but not that much,” Dr. Oldham reported.

Also, in the same sample of patients and using a validated scale measuring difficulty in emotional regulation, both BPD and non-BPD patients are very emotionally dysregulated on admission, albeit BPD patients more so.

After several weeks, the non-borderline patients are in the normal range and the BPD patients are “still not in the normal range, but they are doing much better.”

“Even though almost all of our patients get better, there are some patients who don’t respond even at this level of intensive treatment,” Dr. Oldham concluded, saying that his group also is looking at biomarkers, neuroimaging data, genomics, and the microbiome in an attempt to gain a better understanding of major psychiatric disorders.

Dr. Oldham reported having no financial disclosures.

TORONTO – In patients hospitalized for borderline personality disorder (BPD) and other complex psychiatric disturbances, symptoms of depression and emotional dysregulation continue to progressively improve over several weeks. But at 1 week, the improvement is minimal, which is an issue given that the average psychiatric hospitalization in the United States is only 5 to 7 days.

“So more time [in the hospital] may be something that we have to lobby for,” Dr. John M. Oldham said during a talk at the American Psychiatric Association (APA) annual meeting.

Dr. Oldham showed preliminary results from the Menninger Clinic’s Hospital-Wide Outcomes Project as part of a longer discussion on the current state of personality disorders research. Dr. Oldham is chief of staff and senior vice president at Menninger in Houston. He also is an internationally recognized specialist in personality disorders and a past president of the APA. There is a “fair drumbeat” in the literature and in clinical circles suggesting long hospitalizations should be avoided in BPD patients, because the illness tends to be associated with regression.

“Well, I think that’s good advice, if you can get away with it,” Dr. Oldham said. Unfortunately, some patients will need longer term hospitalization for refractory symptoms, persistent or severe suicidality, self-destructiveness, or nonadherence to treatment, among other indications.

At the Menninger Clinic, all patients are administered structured psychiatric interviews (e.g., the Structured Clinical Interview for DSM-IV Axis I Disorders [SCID-I] and the Structured Clinical Interview for DSM-IV Axis II Disorders [SCID-II] at admission, as well as a battery of self-report tests that provide objective data on clinical symptoms, level of functioning, interpersonal relationships, and treatment progress and process (working relationships with treatment team members and treatment engagement). Symptom and functional assessments are repeated every 2 weeks during hospitalization. Patients are asked to complete a similar battery of self-report measures 2 weeks after discharge and then every 3 months after that for 18 months. More than 1,600 patients have participated in the study since it began in 2008.

“We have an unusual, unique opportunity to do this work, because our average length of stay at the Menninger Clinic for an inpatient is 45 days, which is very unusual in hospital psychiatry these days,” Dr. Oldham said.

“There’s only one way we can do it, and that is that 80% of our patients are self-pay, so [we’re looking at] a layer of a higher socioeconomic bracket because the insurance companies will not pay for longer care.”

The hope of the Menninger investigators is to use their data to make the case that for some patients – and many of the Menninger patients “have not been able to get better with the usual available treatment” – that it’s cost effective to treat these difficult cases for significantly longer periods in hospital.

Progressively reduced symptoms

The Menninger data so far include 255 patients with BPD and 1,129 patients without BPD, and these numbers are steadily increasing. Dr. Oldham explained that the many of the 1,129 non-BDP patients have complex conditions that are generally a mood disorder and an underlying personality disorder and “almost always” a substance abuse issue, too.

In preliminary data shown by Dr. Oldham, the self-administered Patient Health Questionnaire-9 (PHQ-9) depression severity scale is high in both groups on admission, ranking as “severe” in the BPD group and “moderate” in the non-BPD arm.

At 1 week – the length of a usual hospitalization – the BPD patients have dropped to moderate on the scale, and the non-BDP patients to mild, but after 6 weeks, both groups have dropped further on the scale such that the BPD patients have only mild symptoms and the non-BDP patients are approaching normal levels of depressed affect.

“At the 1-week mark … you can see that the patient is a little bit better but not that much,” Dr. Oldham reported.

Also, in the same sample of patients and using a validated scale measuring difficulty in emotional regulation, both BPD and non-BPD patients are very emotionally dysregulated on admission, albeit BPD patients more so.

After several weeks, the non-borderline patients are in the normal range and the BPD patients are “still not in the normal range, but they are doing much better.”

“Even though almost all of our patients get better, there are some patients who don’t respond even at this level of intensive treatment,” Dr. Oldham concluded, saying that his group also is looking at biomarkers, neuroimaging data, genomics, and the microbiome in an attempt to gain a better understanding of major psychiatric disorders.

Dr. Oldham reported having no financial disclosures.

TORONTO – In patients hospitalized for borderline personality disorder (BPD) and other complex psychiatric disturbances, symptoms of depression and emotional dysregulation continue to progressively improve over several weeks. But at 1 week, the improvement is minimal, which is an issue given that the average psychiatric hospitalization in the United States is only 5 to 7 days.

“So more time [in the hospital] may be something that we have to lobby for,” Dr. John M. Oldham said during a talk at the American Psychiatric Association (APA) annual meeting.

Dr. Oldham showed preliminary results from the Menninger Clinic’s Hospital-Wide Outcomes Project as part of a longer discussion on the current state of personality disorders research. Dr. Oldham is chief of staff and senior vice president at Menninger in Houston. He also is an internationally recognized specialist in personality disorders and a past president of the APA. There is a “fair drumbeat” in the literature and in clinical circles suggesting long hospitalizations should be avoided in BPD patients, because the illness tends to be associated with regression.

“Well, I think that’s good advice, if you can get away with it,” Dr. Oldham said. Unfortunately, some patients will need longer term hospitalization for refractory symptoms, persistent or severe suicidality, self-destructiveness, or nonadherence to treatment, among other indications.

At the Menninger Clinic, all patients are administered structured psychiatric interviews (e.g., the Structured Clinical Interview for DSM-IV Axis I Disorders [SCID-I] and the Structured Clinical Interview for DSM-IV Axis II Disorders [SCID-II] at admission, as well as a battery of self-report tests that provide objective data on clinical symptoms, level of functioning, interpersonal relationships, and treatment progress and process (working relationships with treatment team members and treatment engagement). Symptom and functional assessments are repeated every 2 weeks during hospitalization. Patients are asked to complete a similar battery of self-report measures 2 weeks after discharge and then every 3 months after that for 18 months. More than 1,600 patients have participated in the study since it began in 2008.

“We have an unusual, unique opportunity to do this work, because our average length of stay at the Menninger Clinic for an inpatient is 45 days, which is very unusual in hospital psychiatry these days,” Dr. Oldham said.

“There’s only one way we can do it, and that is that 80% of our patients are self-pay, so [we’re looking at] a layer of a higher socioeconomic bracket because the insurance companies will not pay for longer care.”

The hope of the Menninger investigators is to use their data to make the case that for some patients – and many of the Menninger patients “have not been able to get better with the usual available treatment” – that it’s cost effective to treat these difficult cases for significantly longer periods in hospital.

Progressively reduced symptoms

The Menninger data so far include 255 patients with BPD and 1,129 patients without BPD, and these numbers are steadily increasing. Dr. Oldham explained that the many of the 1,129 non-BDP patients have complex conditions that are generally a mood disorder and an underlying personality disorder and “almost always” a substance abuse issue, too.

In preliminary data shown by Dr. Oldham, the self-administered Patient Health Questionnaire-9 (PHQ-9) depression severity scale is high in both groups on admission, ranking as “severe” in the BPD group and “moderate” in the non-BPD arm.

At 1 week – the length of a usual hospitalization – the BPD patients have dropped to moderate on the scale, and the non-BDP patients to mild, but after 6 weeks, both groups have dropped further on the scale such that the BPD patients have only mild symptoms and the non-BDP patients are approaching normal levels of depressed affect.

“At the 1-week mark … you can see that the patient is a little bit better but not that much,” Dr. Oldham reported.

Also, in the same sample of patients and using a validated scale measuring difficulty in emotional regulation, both BPD and non-BPD patients are very emotionally dysregulated on admission, albeit BPD patients more so.

After several weeks, the non-borderline patients are in the normal range and the BPD patients are “still not in the normal range, but they are doing much better.”

“Even though almost all of our patients get better, there are some patients who don’t respond even at this level of intensive treatment,” Dr. Oldham concluded, saying that his group also is looking at biomarkers, neuroimaging data, genomics, and the microbiome in an attempt to gain a better understanding of major psychiatric disorders.

Dr. Oldham reported having no financial disclosures.

TORONTO – The experimental antipsychotic ITI-007 was safe and well tolerated, and improved negative symptoms, depression, and overall symptoms in patients with an acute exacerbation episode of schizophrenia in a phase II trial. Importantly, in patients with prominent negative symptoms of schizophrenia and in those with comorbid depression, ITI-007 appeared to be particularly efficacious, in some cases more so than risperidone, and with better tolerability.

“We believe ITI-007’s serotonergic-dopaminergic-glutamatergic pharmacological profile represents a new approach to the treatment of schizophrenia in a single, stand-alone therapy,” reported Kimberly E. Vanover, Ph.D., vice president of clinical development for Intra-Cellular Therapies, the developers of ITI-007. Dr. Vanover reported updated safety and tolerability findings from the ITI-007-005 trial at the annual meeting of the American Psychiatric Association.

The ITI-007-005 trial was a randomized, double-blind, placebo- and active-controlled clinical trial in patients with a current acutely exacerbated episode of schizophrenia. A total of 335 patients were randomly assigned to one of four treatments: either 60 or 120 mg ITI-007, 4 mg risperidone, or placebo. Patients were hospitalized and received study treatment orally once daily in the morning for 28 days. Of those randomized, 311 patients were included in the intent-to-treat (ITT) primary analysis.

Primary endpoint met

The primary endpoint was the mean change from baseline to day 28 on the 30-item Positive and Negative Syndrome Scale (PANSS) total score, which measures positive symptoms such as delusions, suspiciousness, and hallucinations; negative symptoms, such as blunted affect, social and emotional withdrawal, and stereotyped thinking; and general psychopathology, such as anxiety, tension, depression, and active social avoidance. Safety and tolerability also were assessed.

The trial met its primary endpoint for the lower dose of ITI-007, with a significant reduction in total PANSS at day 28, compared with placebo. Risperidone also reduced total PANSS to a similar extent as ITI-007 60 mg, but the ITI-007 120 mg dose was not found to be more efficacious than placebo. The results were very similar when only the mean change in the PANSS positive subscale was considered.

“We do not fully understand why the higher dose didn’t separate,” Dr. Vanover reported. One consideration is that at the higher dose, more patients experience somnolence or sedation, the most common adverse event seen with the study drug. Since the drug was given in the morning and the PANSS questionnaire required an interview, it could be that the patients treated with the higher doses scored less well on the test just because they were sleepy. “More studies are needed to determine if the 120 dose could be efficacious if given at night,” as most antipsychotics are, Dr. Vanover said.

Improved negative symptoms

Although as an acute schizophrenia trial, ITI-007-005 was not designed to look just at negative symptoms of schizophrenia, the investigators predefined a subgroup population analysis of patients who had prominent negative symptoms at baseline (defined as a score of 4 or more on at least three negative symptom items on the PANSS at baseline).

While ITI-007 60 mg improved negative symptoms in the overall ITT population, in the subgroup of patients who were exhibiting prominent negative symptoms, the improvement was much greater (effect size, 0.34 vs. 0.19 for ITT population).

Notably, risperidone and 120 mg ITI-007 did not improve negative symptoms in this subgroup or in the overall ITT population.

“What we were able to show in this study is that negative symptoms can improve independently from improvements in positive symptoms with no correlation between these two measures,” Dr. Vanover said. “So, we believe you can get improvements in the primary negative symptoms without it being pseudospecific to the positive symptoms, but this needs to be evaluated in future studies in patients with prominent negative symptoms.

Works in comorbid depression

The investigators also looked at the subgroup of patients with comorbid depression, as this represents a particularly vulnerable population with symptoms across multiple domains.

Although the numbers were small, ITI-007 60 mg showed a “rapid, robust, and statistically significant antipsychotic effect not observed with risperidone,” Dr. Vanover said.

“ITI-007 60 mg also constantly and significantly improved depressive symptoms in this subgroup. We did see a numerical improvement with risperidone, but that effect was variable and did not reach statistical significance.”

“So we believe that this subgroup of patients with schizophrenia and comorbid depression may be particularly sensitive and responsive to ITI-007 treatment.”

Indeed, on the total PANSS score, the percentage improvement seen in the depressed subgroup reached 50%, “which is quite robust,” said Dr. Vanover, as a 30% improvement is generally considered clinically significant.

Metabolic profile proves favorable

ITI-007 was considered safe and well tolerated. The side effect profile seen with the 60-mg dose was not significantly different from placebo.

The most common adverse event was sedation/somnolence, reported in 17% of the 60-mg group and in 13% of the placebo arm. Dr. Vanover stressed, however, that these patients were hospitalized “with not a lot to do, so a lot of people were taking naps.” Sedation or somnolence was reported in 32.5% of the ITI-007 120-mg group.

Importantly, ITI-007 given at the lower 60-mg dose showed no difference from placebo on extrapyramidal symptoms (EPS), akathisia, or prolactin levels. Also, no clinically significant changes were found in cardiovascular function noted (no QTc prolongation or sustained increase in heart rate, as is seen with risperidone), and the drug had a favorable weight gain (“little or none”) and metabolic profile.

Phase III studies ongoing

Two phase III clinical trials of ITI-007 are underway. The first will test a 4-week course of ITI-007 40 mg and 60 mg against placebo in 400 inpatients with acutely exacerbated episodes of schizophrenia. The second study, called ITI-007-302, is again using risperidone as an active control and will randomly assign 500 patients with acutely exacerbated episodes of schizophrenia to a 6-week course of ITI-007 20 mg, 60 mg, placebo, or risperidone 4 mg. The primary outcomes for both studies will be the change in mean PANSS total score from baseline.

ITI-007 is a first-in-class molecule that combines potent serotonin 5-hydroxytryptamine_2A–receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic phosphoprotein modulation, and serotonin reuptake inhibition into a single-drug candidate for the treatment of acute and residual schizophrenia.

At low doses, ITI-007 is a very potent serotonin 5-HT_2A–receptor antagonist, Dr. Vanover said. The 5-HT_2A–receptor antagonism improves sleep quality, enhances antipsychotic and antidepressant activity, and reduces anxiety and hostility. As the dose of ITI-007 is increased, other pharmacological targets are engaged, including the activation of DPPM effects.

Dr. Vanover is a full-time employee of ITI.

TORONTO – The experimental antipsychotic ITI-007 was safe and well tolerated, and improved negative symptoms, depression, and overall symptoms in patients with an acute exacerbation episode of schizophrenia in a phase II trial. Importantly, in patients with prominent negative symptoms of schizophrenia and in those with comorbid depression, ITI-007 appeared to be particularly efficacious, in some cases more so than risperidone, and with better tolerability.

“We believe ITI-007’s serotonergic-dopaminergic-glutamatergic pharmacological profile represents a new approach to the treatment of schizophrenia in a single, stand-alone therapy,” reported Kimberly E. Vanover, Ph.D., vice president of clinical development for Intra-Cellular Therapies, the developers of ITI-007. Dr. Vanover reported updated safety and tolerability findings from the ITI-007-005 trial at the annual meeting of the American Psychiatric Association.

The ITI-007-005 trial was a randomized, double-blind, placebo- and active-controlled clinical trial in patients with a current acutely exacerbated episode of schizophrenia. A total of 335 patients were randomly assigned to one of four treatments: either 60 or 120 mg ITI-007, 4 mg risperidone, or placebo. Patients were hospitalized and received study treatment orally once daily in the morning for 28 days. Of those randomized, 311 patients were included in the intent-to-treat (ITT) primary analysis.

Primary endpoint met

The primary endpoint was the mean change from baseline to day 28 on the 30-item Positive and Negative Syndrome Scale (PANSS) total score, which measures positive symptoms such as delusions, suspiciousness, and hallucinations; negative symptoms, such as blunted affect, social and emotional withdrawal, and stereotyped thinking; and general psychopathology, such as anxiety, tension, depression, and active social avoidance. Safety and tolerability also were assessed.

The trial met its primary endpoint for the lower dose of ITI-007, with a significant reduction in total PANSS at day 28, compared with placebo. Risperidone also reduced total PANSS to a similar extent as ITI-007 60 mg, but the ITI-007 120 mg dose was not found to be more efficacious than placebo. The results were very similar when only the mean change in the PANSS positive subscale was considered.

“We do not fully understand why the higher dose didn’t separate,” Dr. Vanover reported. One consideration is that at the higher dose, more patients experience somnolence or sedation, the most common adverse event seen with the study drug. Since the drug was given in the morning and the PANSS questionnaire required an interview, it could be that the patients treated with the higher doses scored less well on the test just because they were sleepy. “More studies are needed to determine if the 120 dose could be efficacious if given at night,” as most antipsychotics are, Dr. Vanover said.

Improved negative symptoms

Although as an acute schizophrenia trial, ITI-007-005 was not designed to look just at negative symptoms of schizophrenia, the investigators predefined a subgroup population analysis of patients who had prominent negative symptoms at baseline (defined as a score of 4 or more on at least three negative symptom items on the PANSS at baseline).

While ITI-007 60 mg improved negative symptoms in the overall ITT population, in the subgroup of patients who were exhibiting prominent negative symptoms, the improvement was much greater (effect size, 0.34 vs. 0.19 for ITT population).

Notably, risperidone and 120 mg ITI-007 did not improve negative symptoms in this subgroup or in the overall ITT population.

“What we were able to show in this study is that negative symptoms can improve independently from improvements in positive symptoms with no correlation between these two measures,” Dr. Vanover said. “So, we believe you can get improvements in the primary negative symptoms without it being pseudospecific to the positive symptoms, but this needs to be evaluated in future studies in patients with prominent negative symptoms.

Works in comorbid depression

The investigators also looked at the subgroup of patients with comorbid depression, as this represents a particularly vulnerable population with symptoms across multiple domains.

Although the numbers were small, ITI-007 60 mg showed a “rapid, robust, and statistically significant antipsychotic effect not observed with risperidone,” Dr. Vanover said.

“ITI-007 60 mg also constantly and significantly improved depressive symptoms in this subgroup. We did see a numerical improvement with risperidone, but that effect was variable and did not reach statistical significance.”

“So we believe that this subgroup of patients with schizophrenia and comorbid depression may be particularly sensitive and responsive to ITI-007 treatment.”

Indeed, on the total PANSS score, the percentage improvement seen in the depressed subgroup reached 50%, “which is quite robust,” said Dr. Vanover, as a 30% improvement is generally considered clinically significant.

Metabolic profile proves favorable

ITI-007 was considered safe and well tolerated. The side effect profile seen with the 60-mg dose was not significantly different from placebo.

The most common adverse event was sedation/somnolence, reported in 17% of the 60-mg group and in 13% of the placebo arm. Dr. Vanover stressed, however, that these patients were hospitalized “with not a lot to do, so a lot of people were taking naps.” Sedation or somnolence was reported in 32.5% of the ITI-007 120-mg group.

Importantly, ITI-007 given at the lower 60-mg dose showed no difference from placebo on extrapyramidal symptoms (EPS), akathisia, or prolactin levels. Also, no clinically significant changes were found in cardiovascular function noted (no QTc prolongation or sustained increase in heart rate, as is seen with risperidone), and the drug had a favorable weight gain (“little or none”) and metabolic profile.

Phase III studies ongoing

Two phase III clinical trials of ITI-007 are underway. The first will test a 4-week course of ITI-007 40 mg and 60 mg against placebo in 400 inpatients with acutely exacerbated episodes of schizophrenia. The second study, called ITI-007-302, is again using risperidone as an active control and will randomly assign 500 patients with acutely exacerbated episodes of schizophrenia to a 6-week course of ITI-007 20 mg, 60 mg, placebo, or risperidone 4 mg. The primary outcomes for both studies will be the change in mean PANSS total score from baseline.

ITI-007 is a first-in-class molecule that combines potent serotonin 5-hydroxytryptamine_2A–receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic phosphoprotein modulation, and serotonin reuptake inhibition into a single-drug candidate for the treatment of acute and residual schizophrenia.

At low doses, ITI-007 is a very potent serotonin 5-HT_2A–receptor antagonist, Dr. Vanover said. The 5-HT_2A–receptor antagonism improves sleep quality, enhances antipsychotic and antidepressant activity, and reduces anxiety and hostility. As the dose of ITI-007 is increased, other pharmacological targets are engaged, including the activation of DPPM effects.

Dr. Vanover is a full-time employee of ITI.

TORONTO – The experimental antipsychotic ITI-007 was safe and well tolerated, and improved negative symptoms, depression, and overall symptoms in patients with an acute exacerbation episode of schizophrenia in a phase II trial. Importantly, in patients with prominent negative symptoms of schizophrenia and in those with comorbid depression, ITI-007 appeared to be particularly efficacious, in some cases more so than risperidone, and with better tolerability.

“We believe ITI-007’s serotonergic-dopaminergic-glutamatergic pharmacological profile represents a new approach to the treatment of schizophrenia in a single, stand-alone therapy,” reported Kimberly E. Vanover, Ph.D., vice president of clinical development for Intra-Cellular Therapies, the developers of ITI-007. Dr. Vanover reported updated safety and tolerability findings from the ITI-007-005 trial at the annual meeting of the American Psychiatric Association.

The ITI-007-005 trial was a randomized, double-blind, placebo- and active-controlled clinical trial in patients with a current acutely exacerbated episode of schizophrenia. A total of 335 patients were randomly assigned to one of four treatments: either 60 or 120 mg ITI-007, 4 mg risperidone, or placebo. Patients were hospitalized and received study treatment orally once daily in the morning for 28 days. Of those randomized, 311 patients were included in the intent-to-treat (ITT) primary analysis.

Primary endpoint met

The primary endpoint was the mean change from baseline to day 28 on the 30-item Positive and Negative Syndrome Scale (PANSS) total score, which measures positive symptoms such as delusions, suspiciousness, and hallucinations; negative symptoms, such as blunted affect, social and emotional withdrawal, and stereotyped thinking; and general psychopathology, such as anxiety, tension, depression, and active social avoidance. Safety and tolerability also were assessed.

The trial met its primary endpoint for the lower dose of ITI-007, with a significant reduction in total PANSS at day 28, compared with placebo. Risperidone also reduced total PANSS to a similar extent as ITI-007 60 mg, but the ITI-007 120 mg dose was not found to be more efficacious than placebo. The results were very similar when only the mean change in the PANSS positive subscale was considered.

“We do not fully understand why the higher dose didn’t separate,” Dr. Vanover reported. One consideration is that at the higher dose, more patients experience somnolence or sedation, the most common adverse event seen with the study drug. Since the drug was given in the morning and the PANSS questionnaire required an interview, it could be that the patients treated with the higher doses scored less well on the test just because they were sleepy. “More studies are needed to determine if the 120 dose could be efficacious if given at night,” as most antipsychotics are, Dr. Vanover said.

Improved negative symptoms

Although as an acute schizophrenia trial, ITI-007-005 was not designed to look just at negative symptoms of schizophrenia, the investigators predefined a subgroup population analysis of patients who had prominent negative symptoms at baseline (defined as a score of 4 or more on at least three negative symptom items on the PANSS at baseline).

While ITI-007 60 mg improved negative symptoms in the overall ITT population, in the subgroup of patients who were exhibiting prominent negative symptoms, the improvement was much greater (effect size, 0.34 vs. 0.19 for ITT population).

Notably, risperidone and 120 mg ITI-007 did not improve negative symptoms in this subgroup or in the overall ITT population.

“What we were able to show in this study is that negative symptoms can improve independently from improvements in positive symptoms with no correlation between these two measures,” Dr. Vanover said. “So, we believe you can get improvements in the primary negative symptoms without it being pseudospecific to the positive symptoms, but this needs to be evaluated in future studies in patients with prominent negative symptoms.

Works in comorbid depression

The investigators also looked at the subgroup of patients with comorbid depression, as this represents a particularly vulnerable population with symptoms across multiple domains.

Although the numbers were small, ITI-007 60 mg showed a “rapid, robust, and statistically significant antipsychotic effect not observed with risperidone,” Dr. Vanover said.

“ITI-007 60 mg also constantly and significantly improved depressive symptoms in this subgroup. We did see a numerical improvement with risperidone, but that effect was variable and did not reach statistical significance.”

“So we believe that this subgroup of patients with schizophrenia and comorbid depression may be particularly sensitive and responsive to ITI-007 treatment.”

Indeed, on the total PANSS score, the percentage improvement seen in the depressed subgroup reached 50%, “which is quite robust,” said Dr. Vanover, as a 30% improvement is generally considered clinically significant.

Metabolic profile proves favorable

ITI-007 was considered safe and well tolerated. The side effect profile seen with the 60-mg dose was not significantly different from placebo.

The most common adverse event was sedation/somnolence, reported in 17% of the 60-mg group and in 13% of the placebo arm. Dr. Vanover stressed, however, that these patients were hospitalized “with not a lot to do, so a lot of people were taking naps.” Sedation or somnolence was reported in 32.5% of the ITI-007 120-mg group.

Importantly, ITI-007 given at the lower 60-mg dose showed no difference from placebo on extrapyramidal symptoms (EPS), akathisia, or prolactin levels. Also, no clinically significant changes were found in cardiovascular function noted (no QTc prolongation or sustained increase in heart rate, as is seen with risperidone), and the drug had a favorable weight gain (“little or none”) and metabolic profile.

Phase III studies ongoing

Two phase III clinical trials of ITI-007 are underway. The first will test a 4-week course of ITI-007 40 mg and 60 mg against placebo in 400 inpatients with acutely exacerbated episodes of schizophrenia. The second study, called ITI-007-302, is again using risperidone as an active control and will randomly assign 500 patients with acutely exacerbated episodes of schizophrenia to a 6-week course of ITI-007 20 mg, 60 mg, placebo, or risperidone 4 mg. The primary outcomes for both studies will be the change in mean PANSS total score from baseline.

ITI-007 is a first-in-class molecule that combines potent serotonin 5-hydroxytryptamine_2A–receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic phosphoprotein modulation, and serotonin reuptake inhibition into a single-drug candidate for the treatment of acute and residual schizophrenia.

At low doses, ITI-007 is a very potent serotonin 5-HT_2A–receptor antagonist, Dr. Vanover said. The 5-HT_2A–receptor antagonism improves sleep quality, enhances antipsychotic and antidepressant activity, and reduces anxiety and hostility. As the dose of ITI-007 is increased, other pharmacological targets are engaged, including the activation of DPPM effects.

Dr. Vanover is a full-time employee of ITI.

TORONTO – Operative mortality with total aortic arch replacement using a four-branched graft and frozen elephant trunk implantation (Sun’s procedure) was 6.5%, including those whose type A aortic dissection was defined as acute.

Operative mortality was higher in acute versus chronic type A aortic dissection (TAAD) patients undergoing the procedure (8.1% vs. 4.3%; P = .031), as was the incidence of stroke (2.2% vs. 0.6%; P = .046), and respiratory complications (20.8% vs. 8.6%; P less than .001).

However, although the risk of operative mortality in acute patients was 1.95 times higher than for chronic patients, in multivariate analysis, acuteness was not identified as a significant risk factor for operative mortality (odds ratio, 1.67; P = .152).

The factors identified as increasing risk of operative mortality were coexisting cerebrovascular disease; malperfusion of the brain, kidneys, spinal cord, and viscera; concomitant extra-anatomic bypass; and cardiopulmonary bypass time exceeding 180 minutes.

"This study proves the safety of frozen elephant trunk with total arch replacement," said Dr. Wei-Guo Ma of Yale University, New Haven, Conn.

"Operative mortality was not affected by either the acute or chronic phase. Instead it was affected by seven other factors, such as prior CVD [cerebrovascular disease], malperfusion, and longer CPB [cardiopulmonary bypass] time.

"If a patient comes without those risk factors, surgeons can go ahead and perform this emergent frozen elephant trunk for him without fear of imposing greater risk of mortality," he said.

Standard TAAD remains a highly lethal condition, with the greatest surgical risk seen during the acute phase. Although some progress has been made, surgeons continue to debate the optimal surgical approach to TAAD, in particular the extent of distal aortic repair. Some advocate a more limited approach of hemiarch repair only, while others propose that total arch repair offers better outcomes.

Sun’s procedure is performed with right axillary artery cannulation for cardiopulmonary bypass and selective antegrade cerebral perfusion, under moderate hypothermic circulatory arrest at 25° C.

The frozen elephant trunk (Cronus, MicroPort Medical, Shanghai, China) is implanted into the descending aorta, followed by total arch replacement using a four-branched vascular graft, with a special sequence for aortic reconstruction (i.e., proximal descending aorta to left carotid artery to ascending aorta to left subclavian artery to innominate artery). Associated operations, including coronary artery bypass grafting, are performed during the cooling phase, if needed.

In this case series, presented by Dr. Ma at the annual meeting of the American Association for Thoracic Surgery, acuteness was defined as an interval between onset of symptoms and surgery of 14 days or less.

TAAD was diagnosed preoperatively by transthoracic echocardiography or computed tomographic angiography, with the location of the intimal tear confirmed during surgery.

The surgeons retrospectively compared early outcomes between acute and chronic TAAD patients after Sun’s procedure, seeking to identify risk factors for operative mortality in both groups and seeking to determine whether acuteness significantly affects operative mortality after this extensive surgical approach.

Between April 2003 and September 2012, Sun’s procedure was performed on 803 patients with acute or chronic TAAD. Mean age was 46 years and 80% of the cohort was male. A total of 456 were classified as acute TAAD patients, with a mean of 5.5 days lapsing between onset of symptoms to surgery (median, 4.1 days), and 347 were chronic, with 197 days lapsing between onset of symptoms and surgery (median, 38 days).

Clinically apparent malperfusion was common, seen in 12.6% of cases, 12.3% of the acute arm and 9.2% of the chronic arm. Patients with malperfusion had an overall mortality of 19.3% (25% in the acute arm and 9.4% in the chronic arm; P less than .001).

"Visceral malperfusion tended to be the most lethal, with five of seven patients dying," reported Dr. Ma. He also noted the young age of their cohort as compared to other regions of the world: 88.8% of patients were under 60 years of age.

Acute, minus natural selection

The invited discussant on the abstract, Dr. Malakh L. Shrestha took issue with the study’s conclusion that acuteness did not affect operative mortality. Dr. Shrestha is the division manager of valvular and coronary artery surgery at the Hannover (Germany) Medical School.

"As a high volume center, what we’ve learned is that acute and chronic aortic dissection patients are two totally different subsets of patients in terms of clinical presentation and mortality. The greatest danger in the acute patient is in the first few hours after the dissection, with the majority of patients dying without surgical intervention."

At Dr. Shrestha’s center in Germany, a high-volume aortic center, they often see patients within the first few hours of their dissection and they’ve found a significantly higher mortality in these patients, compared with chronic TAAD whether an ascending aortic replacement or a frozen elephant trunk procedure is done.

With a median of 4.1 days lapsing between onset of symptoms and surgery in the Ma et al. study, Dr. Shrestha argued that "although on the basis of classification, you can still say they’re acute, there has been some sort of natural selection. So, I think that means, at least for your conclusions, that you need to clarify the statement that there is no difference between acute and chronic, because these are obviously not the same subset of patients that we see in the Western world."

Dr. Ma agreed that natural selection was indeed at play in their series, in that about 80% of their patients were referrals that were transferred in some cases from hundreds of miles away, with many dying en route or before surgery. He also concurred that had their mean and median number of days in their acute cohort been less, indeed, mortality might have been higher.

Dr. Ma reported having no conflicts of interest. Dr. Shrestha is a consultant for Edwards Lifesciences.

TORONTO – Operative mortality with total aortic arch replacement using a four-branched graft and frozen elephant trunk implantation (Sun’s procedure) was 6.5%, including those whose type A aortic dissection was defined as acute.

Operative mortality was higher in acute versus chronic type A aortic dissection (TAAD) patients undergoing the procedure (8.1% vs. 4.3%; P = .031), as was the incidence of stroke (2.2% vs. 0.6%; P = .046), and respiratory complications (20.8% vs. 8.6%; P less than .001).

However, although the risk of operative mortality in acute patients was 1.95 times higher than for chronic patients, in multivariate analysis, acuteness was not identified as a significant risk factor for operative mortality (odds ratio, 1.67; P = .152).

The factors identified as increasing risk of operative mortality were coexisting cerebrovascular disease; malperfusion of the brain, kidneys, spinal cord, and viscera; concomitant extra-anatomic bypass; and cardiopulmonary bypass time exceeding 180 minutes.

"This study proves the safety of frozen elephant trunk with total arch replacement," said Dr. Wei-Guo Ma of Yale University, New Haven, Conn.

"Operative mortality was not affected by either the acute or chronic phase. Instead it was affected by seven other factors, such as prior CVD [cerebrovascular disease], malperfusion, and longer CPB [cardiopulmonary bypass] time.

"If a patient comes without those risk factors, surgeons can go ahead and perform this emergent frozen elephant trunk for him without fear of imposing greater risk of mortality," he said.

Standard TAAD remains a highly lethal condition, with the greatest surgical risk seen during the acute phase. Although some progress has been made, surgeons continue to debate the optimal surgical approach to TAAD, in particular the extent of distal aortic repair. Some advocate a more limited approach of hemiarch repair only, while others propose that total arch repair offers better outcomes.

Sun’s procedure is performed with right axillary artery cannulation for cardiopulmonary bypass and selective antegrade cerebral perfusion, under moderate hypothermic circulatory arrest at 25° C.

The frozen elephant trunk (Cronus, MicroPort Medical, Shanghai, China) is implanted into the descending aorta, followed by total arch replacement using a four-branched vascular graft, with a special sequence for aortic reconstruction (i.e., proximal descending aorta to left carotid artery to ascending aorta to left subclavian artery to innominate artery). Associated operations, including coronary artery bypass grafting, are performed during the cooling phase, if needed.

In this case series, presented by Dr. Ma at the annual meeting of the American Association for Thoracic Surgery, acuteness was defined as an interval between onset of symptoms and surgery of 14 days or less.

TAAD was diagnosed preoperatively by transthoracic echocardiography or computed tomographic angiography, with the location of the intimal tear confirmed during surgery.

The surgeons retrospectively compared early outcomes between acute and chronic TAAD patients after Sun’s procedure, seeking to identify risk factors for operative mortality in both groups and seeking to determine whether acuteness significantly affects operative mortality after this extensive surgical approach.

Between April 2003 and September 2012, Sun’s procedure was performed on 803 patients with acute or chronic TAAD. Mean age was 46 years and 80% of the cohort was male. A total of 456 were classified as acute TAAD patients, with a mean of 5.5 days lapsing between onset of symptoms to surgery (median, 4.1 days), and 347 were chronic, with 197 days lapsing between onset of symptoms and surgery (median, 38 days).

Clinically apparent malperfusion was common, seen in 12.6% of cases, 12.3% of the acute arm and 9.2% of the chronic arm. Patients with malperfusion had an overall mortality of 19.3% (25% in the acute arm and 9.4% in the chronic arm; P less than .001).

"Visceral malperfusion tended to be the most lethal, with five of seven patients dying," reported Dr. Ma. He also noted the young age of their cohort as compared to other regions of the world: 88.8% of patients were under 60 years of age.

Acute, minus natural selection

The invited discussant on the abstract, Dr. Malakh L. Shrestha took issue with the study’s conclusion that acuteness did not affect operative mortality. Dr. Shrestha is the division manager of valvular and coronary artery surgery at the Hannover (Germany) Medical School.

"As a high volume center, what we’ve learned is that acute and chronic aortic dissection patients are two totally different subsets of patients in terms of clinical presentation and mortality. The greatest danger in the acute patient is in the first few hours after the dissection, with the majority of patients dying without surgical intervention."

At Dr. Shrestha’s center in Germany, a high-volume aortic center, they often see patients within the first few hours of their dissection and they’ve found a significantly higher mortality in these patients, compared with chronic TAAD whether an ascending aortic replacement or a frozen elephant trunk procedure is done.

With a median of 4.1 days lapsing between onset of symptoms and surgery in the Ma et al. study, Dr. Shrestha argued that "although on the basis of classification, you can still say they’re acute, there has been some sort of natural selection. So, I think that means, at least for your conclusions, that you need to clarify the statement that there is no difference between acute and chronic, because these are obviously not the same subset of patients that we see in the Western world."

Dr. Ma agreed that natural selection was indeed at play in their series, in that about 80% of their patients were referrals that were transferred in some cases from hundreds of miles away, with many dying en route or before surgery. He also concurred that had their mean and median number of days in their acute cohort been less, indeed, mortality might have been higher.

Dr. Ma reported having no conflicts of interest. Dr. Shrestha is a consultant for Edwards Lifesciences.

TORONTO – Operative mortality with total aortic arch replacement using a four-branched graft and frozen elephant trunk implantation (Sun’s procedure) was 6.5%, including those whose type A aortic dissection was defined as acute.

Operative mortality was higher in acute versus chronic type A aortic dissection (TAAD) patients undergoing the procedure (8.1% vs. 4.3%; P = .031), as was the incidence of stroke (2.2% vs. 0.6%; P = .046), and respiratory complications (20.8% vs. 8.6%; P less than .001).

However, although the risk of operative mortality in acute patients was 1.95 times higher than for chronic patients, in multivariate analysis, acuteness was not identified as a significant risk factor for operative mortality (odds ratio, 1.67; P = .152).

The factors identified as increasing risk of operative mortality were coexisting cerebrovascular disease; malperfusion of the brain, kidneys, spinal cord, and viscera; concomitant extra-anatomic bypass; and cardiopulmonary bypass time exceeding 180 minutes.

"This study proves the safety of frozen elephant trunk with total arch replacement," said Dr. Wei-Guo Ma of Yale University, New Haven, Conn.

"Operative mortality was not affected by either the acute or chronic phase. Instead it was affected by seven other factors, such as prior CVD [cerebrovascular disease], malperfusion, and longer CPB [cardiopulmonary bypass] time.

"If a patient comes without those risk factors, surgeons can go ahead and perform this emergent frozen elephant trunk for him without fear of imposing greater risk of mortality," he said.

Standard TAAD remains a highly lethal condition, with the greatest surgical risk seen during the acute phase. Although some progress has been made, surgeons continue to debate the optimal surgical approach to TAAD, in particular the extent of distal aortic repair. Some advocate a more limited approach of hemiarch repair only, while others propose that total arch repair offers better outcomes.

Sun’s procedure is performed with right axillary artery cannulation for cardiopulmonary bypass and selective antegrade cerebral perfusion, under moderate hypothermic circulatory arrest at 25° C.

The frozen elephant trunk (Cronus, MicroPort Medical, Shanghai, China) is implanted into the descending aorta, followed by total arch replacement using a four-branched vascular graft, with a special sequence for aortic reconstruction (i.e., proximal descending aorta to left carotid artery to ascending aorta to left subclavian artery to innominate artery). Associated operations, including coronary artery bypass grafting, are performed during the cooling phase, if needed.

In this case series, presented by Dr. Ma at the annual meeting of the American Association for Thoracic Surgery, acuteness was defined as an interval between onset of symptoms and surgery of 14 days or less.

TAAD was diagnosed preoperatively by transthoracic echocardiography or computed tomographic angiography, with the location of the intimal tear confirmed during surgery.

The surgeons retrospectively compared early outcomes between acute and chronic TAAD patients after Sun’s procedure, seeking to identify risk factors for operative mortality in both groups and seeking to determine whether acuteness significantly affects operative mortality after this extensive surgical approach.

Between April 2003 and September 2012, Sun’s procedure was performed on 803 patients with acute or chronic TAAD. Mean age was 46 years and 80% of the cohort was male. A total of 456 were classified as acute TAAD patients, with a mean of 5.5 days lapsing between onset of symptoms to surgery (median, 4.1 days), and 347 were chronic, with 197 days lapsing between onset of symptoms and surgery (median, 38 days).

Clinically apparent malperfusion was common, seen in 12.6% of cases, 12.3% of the acute arm and 9.2% of the chronic arm. Patients with malperfusion had an overall mortality of 19.3% (25% in the acute arm and 9.4% in the chronic arm; P less than .001).

"Visceral malperfusion tended to be the most lethal, with five of seven patients dying," reported Dr. Ma. He also noted the young age of their cohort as compared to other regions of the world: 88.8% of patients were under 60 years of age.

Acute, minus natural selection

The invited discussant on the abstract, Dr. Malakh L. Shrestha took issue with the study’s conclusion that acuteness did not affect operative mortality. Dr. Shrestha is the division manager of valvular and coronary artery surgery at the Hannover (Germany) Medical School.

"As a high volume center, what we’ve learned is that acute and chronic aortic dissection patients are two totally different subsets of patients in terms of clinical presentation and mortality. The greatest danger in the acute patient is in the first few hours after the dissection, with the majority of patients dying without surgical intervention."

At Dr. Shrestha’s center in Germany, a high-volume aortic center, they often see patients within the first few hours of their dissection and they’ve found a significantly higher mortality in these patients, compared with chronic TAAD whether an ascending aortic replacement or a frozen elephant trunk procedure is done.

With a median of 4.1 days lapsing between onset of symptoms and surgery in the Ma et al. study, Dr. Shrestha argued that "although on the basis of classification, you can still say they’re acute, there has been some sort of natural selection. So, I think that means, at least for your conclusions, that you need to clarify the statement that there is no difference between acute and chronic, because these are obviously not the same subset of patients that we see in the Western world."

Dr. Ma agreed that natural selection was indeed at play in their series, in that about 80% of their patients were referrals that were transferred in some cases from hundreds of miles away, with many dying en route or before surgery. He also concurred that had their mean and median number of days in their acute cohort been less, indeed, mortality might have been higher.

Dr. Ma reported having no conflicts of interest. Dr. Shrestha is a consultant for Edwards Lifesciences.

TORONTO – Early postoperative left ventricular dysfunction occurs in about 18% of patients who undergo "early" mitral valve repair for severe degenerative disease and have normal preoperative ejection fractions exceeding 60%.

In two-thirds of these patients, the left ventricular dysfunction is persistent and associated with increased mortality, reported Dr. Rakesh Suri of the Mayo Clinic in Rochester, Minn.

"These results may help redefine what we have held true for the last few decades," Dr. David H. Adams said after hearing the data presented at the annual meeting of the American Association for Thoracic Surgery.

Dr. Adams is program director of the Mitral Valve Repair Center, Mount Sinai Medical Center, New York.

Guidelines from the American College of Cardiology/American Heart Association recommend that, for patients with severe degenerative mitral regurgitation due to leaflet prolapse, mitral valve repair needs to be done before the onset of left ventricular dysfunction.

However, despite this preemptive approach, a proportion of patients experience a profound decrease in left ventricular ejection fraction (LVEF), to less than 50% in the immediate postoperative period.

Dr. Suri and his colleagues studied the incidence, predictors, and short- and long-term consequences of this phenomenon in 1,705 patients with severe degenerative mitral regurgitation but LVEF greater than 60% who underwent mitral valve repair at the Mayo Clinic from Jan. 1, 1993, to June 30, 2012.

Patients were excluded from the study if they were under age 18, had a history of significant coronary artery disease, or were undergoing concomitant cardiac procedures other than Maze, tricuspid valve repair, or closure of a patent foramen ovale, the researchers noted.

After mitral valve repair, 82% of the cohort had normal LVEF (50% or more), and 18% developed early LV dysfunction (less than 50%).

Mean preoperative LVEF was 65.8% in the group that maintained normal ejection fraction post repair and 66.3% in the group that developed LV dysfunction (P less than .001).

In the group of patients in whom an early decline in LV function was noted, the mean fall in LVEF was 36%, compared with a postrepair drop of 11% in patients whose function remained in the normal range (P less than .001).

When the researchers looked at whether or not patients went to surgery with guideline-based class I or IIa triggers for mitral valve repair, those being symptoms of LV dysfunction, atrial fibrillation, or pulmonary hypertension, they found that 37% of patients who did not develop LV dysfunction and 22% of those who did had no class I or IIa triggers.

"In other words, the guidelines were incapable of defining this population prior to the performance of mitral valve repair," Dr. Suri explained.

On multivariate analysis, predictors of early LV dysfunction were higher right ventricular systolic pressure and LV end-systolic dimension (both P less than .001).

Patients with early LV dysfunction continued to have significantly diminished LVEF at less than 5, 5-10, and less than 10 years.

"Examined in terms of the ability to recover a normal ejection fraction with time, we saw that amongst those with no LV dysfunction following mitral valve repair, two-thirds went on to complete recovery," explained Dr. Suri.

"In contrast, among those with early LV dysfunction, only one-third were capable of recovering normal LV function with time. In other words, two-thirds had persistent LV dysfunction despite undergoing ‘early’ mitral valve repair," Dr. Suri said.

Early LVEF of less than 40% was seen to increased late mortality risk by 70%.

According to these data, a "normal" preoperative ejection fraction should not provide false reassurance of the capacity for restoration of LV function late following mitral valve repair, suggesting that surgical intervention prior to the onset of excessive LV dilation or pulmonary hypertension is warranted, Dr. Suri said.

"So much of the evidence base that serves as a foundation for the ACC/AHA guidelines comes from the Mayo experience, and your new data is provocative and will have implications for future guidelines," said Dr. Adams, the invited discussant for the abstract.

Dr. Suri reported having no disclosures related to this presentation.

TORONTO – Early postoperative left ventricular dysfunction occurs in about 18% of patients who undergo "early" mitral valve repair for severe degenerative disease and have normal preoperative ejection fractions exceeding 60%.

In two-thirds of these patients, the left ventricular dysfunction is persistent and associated with increased mortality, reported Dr. Rakesh Suri of the Mayo Clinic in Rochester, Minn.

"These results may help redefine what we have held true for the last few decades," Dr. David H. Adams said after hearing the data presented at the annual meeting of the American Association for Thoracic Surgery.

Dr. Adams is program director of the Mitral Valve Repair Center, Mount Sinai Medical Center, New York.

Guidelines from the American College of Cardiology/American Heart Association recommend that, for patients with severe degenerative mitral regurgitation due to leaflet prolapse, mitral valve repair needs to be done before the onset of left ventricular dysfunction.

However, despite this preemptive approach, a proportion of patients experience a profound decrease in left ventricular ejection fraction (LVEF), to less than 50% in the immediate postoperative period.

Dr. Suri and his colleagues studied the incidence, predictors, and short- and long-term consequences of this phenomenon in 1,705 patients with severe degenerative mitral regurgitation but LVEF greater than 60% who underwent mitral valve repair at the Mayo Clinic from Jan. 1, 1993, to June 30, 2012.

Patients were excluded from the study if they were under age 18, had a history of significant coronary artery disease, or were undergoing concomitant cardiac procedures other than Maze, tricuspid valve repair, or closure of a patent foramen ovale, the researchers noted.

After mitral valve repair, 82% of the cohort had normal LVEF (50% or more), and 18% developed early LV dysfunction (less than 50%).

Mean preoperative LVEF was 65.8% in the group that maintained normal ejection fraction post repair and 66.3% in the group that developed LV dysfunction (P less than .001).

In the group of patients in whom an early decline in LV function was noted, the mean fall in LVEF was 36%, compared with a postrepair drop of 11% in patients whose function remained in the normal range (P less than .001).

When the researchers looked at whether or not patients went to surgery with guideline-based class I or IIa triggers for mitral valve repair, those being symptoms of LV dysfunction, atrial fibrillation, or pulmonary hypertension, they found that 37% of patients who did not develop LV dysfunction and 22% of those who did had no class I or IIa triggers.

"In other words, the guidelines were incapable of defining this population prior to the performance of mitral valve repair," Dr. Suri explained.

On multivariate analysis, predictors of early LV dysfunction were higher right ventricular systolic pressure and LV end-systolic dimension (both P less than .001).

Patients with early LV dysfunction continued to have significantly diminished LVEF at less than 5, 5-10, and less than 10 years.

"Examined in terms of the ability to recover a normal ejection fraction with time, we saw that amongst those with no LV dysfunction following mitral valve repair, two-thirds went on to complete recovery," explained Dr. Suri.

"In contrast, among those with early LV dysfunction, only one-third were capable of recovering normal LV function with time. In other words, two-thirds had persistent LV dysfunction despite undergoing ‘early’ mitral valve repair," Dr. Suri said.

Early LVEF of less than 40% was seen to increased late mortality risk by 70%.

According to these data, a "normal" preoperative ejection fraction should not provide false reassurance of the capacity for restoration of LV function late following mitral valve repair, suggesting that surgical intervention prior to the onset of excessive LV dilation or pulmonary hypertension is warranted, Dr. Suri said.

"So much of the evidence base that serves as a foundation for the ACC/AHA guidelines comes from the Mayo experience, and your new data is provocative and will have implications for future guidelines," said Dr. Adams, the invited discussant for the abstract.

Dr. Suri reported having no disclosures related to this presentation.

TORONTO – Early postoperative left ventricular dysfunction occurs in about 18% of patients who undergo "early" mitral valve repair for severe degenerative disease and have normal preoperative ejection fractions exceeding 60%.

In two-thirds of these patients, the left ventricular dysfunction is persistent and associated with increased mortality, reported Dr. Rakesh Suri of the Mayo Clinic in Rochester, Minn.

"These results may help redefine what we have held true for the last few decades," Dr. David H. Adams said after hearing the data presented at the annual meeting of the American Association for Thoracic Surgery.

Dr. Adams is program director of the Mitral Valve Repair Center, Mount Sinai Medical Center, New York.

Guidelines from the American College of Cardiology/American Heart Association recommend that, for patients with severe degenerative mitral regurgitation due to leaflet prolapse, mitral valve repair needs to be done before the onset of left ventricular dysfunction.

However, despite this preemptive approach, a proportion of patients experience a profound decrease in left ventricular ejection fraction (LVEF), to less than 50% in the immediate postoperative period.

Dr. Suri and his colleagues studied the incidence, predictors, and short- and long-term consequences of this phenomenon in 1,705 patients with severe degenerative mitral regurgitation but LVEF greater than 60% who underwent mitral valve repair at the Mayo Clinic from Jan. 1, 1993, to June 30, 2012.

Patients were excluded from the study if they were under age 18, had a history of significant coronary artery disease, or were undergoing concomitant cardiac procedures other than Maze, tricuspid valve repair, or closure of a patent foramen ovale, the researchers noted.

After mitral valve repair, 82% of the cohort had normal LVEF (50% or more), and 18% developed early LV dysfunction (less than 50%).

Mean preoperative LVEF was 65.8% in the group that maintained normal ejection fraction post repair and 66.3% in the group that developed LV dysfunction (P less than .001).

In the group of patients in whom an early decline in LV function was noted, the mean fall in LVEF was 36%, compared with a postrepair drop of 11% in patients whose function remained in the normal range (P less than .001).

When the researchers looked at whether or not patients went to surgery with guideline-based class I or IIa triggers for mitral valve repair, those being symptoms of LV dysfunction, atrial fibrillation, or pulmonary hypertension, they found that 37% of patients who did not develop LV dysfunction and 22% of those who did had no class I or IIa triggers.

"In other words, the guidelines were incapable of defining this population prior to the performance of mitral valve repair," Dr. Suri explained.

On multivariate analysis, predictors of early LV dysfunction were higher right ventricular systolic pressure and LV end-systolic dimension (both P less than .001).

Patients with early LV dysfunction continued to have significantly diminished LVEF at less than 5, 5-10, and less than 10 years.

"Examined in terms of the ability to recover a normal ejection fraction with time, we saw that amongst those with no LV dysfunction following mitral valve repair, two-thirds went on to complete recovery," explained Dr. Suri.

"In contrast, among those with early LV dysfunction, only one-third were capable of recovering normal LV function with time. In other words, two-thirds had persistent LV dysfunction despite undergoing ‘early’ mitral valve repair," Dr. Suri said.

Early LVEF of less than 40% was seen to increased late mortality risk by 70%.

According to these data, a "normal" preoperative ejection fraction should not provide false reassurance of the capacity for restoration of LV function late following mitral valve repair, suggesting that surgical intervention prior to the onset of excessive LV dilation or pulmonary hypertension is warranted, Dr. Suri said.

"So much of the evidence base that serves as a foundation for the ACC/AHA guidelines comes from the Mayo experience, and your new data is provocative and will have implications for future guidelines," said Dr. Adams, the invited discussant for the abstract.

Dr. Suri reported having no disclosures related to this presentation.

TORONTO – In the United States, fewer than one in five coronary artery bypass graft surgeries are done without cardiopulmonary bypass, according to a large Society of Thoracic Surgeons database study conducted by Dr. Faisal G. Bakaeen of Baylor College of Medicine, the Michael E. DeBakey VA Medical Center, and the Texas Heart Institute, Houston, and colleagues.

As of 2012, 84% of the centers in the United States were doing either 0 or fewer than 50 off-pump cases per year. Among U.S. surgeons, 86% did either no off-pump coronary artery bypass grafts (CABG) or 20 or fewer cases per year.

"We speculate that this decline is because off-pump is technically a more demanding operation than on-pump," said Dr. Bakaeen during his presentation at the annual meeting of the American Association of Thoracic Surgery.

"There are [also] concerns about graft patency and the completeness of revascularization and randomized, controlled trials have shown no mortality or major – and I emphasize major – morbidity benefit."

The invited discussant for the abstract, Dr. Harold L. Lazar, the director of cardiothoracic surgery research at Boston Medical Center, suggested that off-pump CABG numbers "will continue to decline" as overall CABG volume continues to decline, and as higher-volume centers and surgeons opt to do fewer off-pump cases.

"Cardiac surgeons have always been motivated to adopt new techniques that will result in improved outcomes for their patients," said Dr. Lazar. "The continuing decline in the use of OP-CABG [off-pump CABG ] by U.S. surgeons is an indication that OP-CABG is not this type of technique."

Introduced in the early 1990s, off-pump CABG was initially touted as a means of avoiding several of the adverse effects of cardiopulmonary bypass and aortic manipulation. However, the relative benefits of off-pump as compared to on-pump CABG continue to be hotly debated.

Dr. Bakaeen and colleagues used the Society of Thoracic Surgeons Adult Cardiac Surgery Database to examine national trends in the use of off- versus on-pump CABG, looking specifically at volume-specific trends among centers and surgeons.

"This is a megadatabase with a huge number of patients, over 2.1 million patients and over 1,200 centers," said Dr. Bakaeen.

The off-pump and on-pump CABG percentages were calculated in aggregate, by center, and by surgeon for a total of 2,137,841 isolated primary CABG procedures performed between Jan. 1, 1997 and Sept. 30, 2012.

Based on 2007/2008 yearly off-pump volume, the analysis subgroups were "high" [center number greater than 200 cases, surgeon number greater than 100 cases], "intermediate" [center number equals 50-200, surgeon number equals 20-100], and "low" [center number less than 50, surgeon number less than 20].

The utilization of off-pump peaked in 2002 at about 23% but then decreased to 17% in 2012. Most of this decrease was found to be driven by higher-volume centers and higher-volume surgeons doing fewer off-pump cases.

Indeed, for the most recent years studied (2011-2012), 12% of U.S. centers (1,056) and 34% of U.S. surgeons (2,626) did not do any off-pump CABG cases.

Another 72% of centers and 52% of surgeons were low-volume operators (less than 50 cases/year and less than 20 cases/year, respectively.

Only 1% of centers (150) and 1% of surgeons (38) were classified as high-volume off-pump operators.

Of note, while the overall conversion rate – cases that were started as on- or off-pump and switched midprocedure – has remained fairly steady at 6%, the rate of unplanned conversions has risen from a low of about 1% in 2004 to about 3.2% in 2012.

"What was interesting was that there was a direct correlation between off-pump volume and the experience of the surgeon and the conversion rate," reported Dr. Bakaeen.

"So, if you are a higher-volume, experienced off-pump surgeon, you are three times less likely to convert than a low-volume surgeon [P less than .01]."

Dr. Bakaeen concluded that, "off-pump CABG utilization will likely continue to be concentrated in specialized centers and performed by dedicated off-pump surgeons."

Dr. Lazar added: "No operation that can only be performed by a select group of experienced, talented surgeons has ever achieved the test of time. CABG surgery must be performed expertly under all circumstances in all patients and at all hospitals, regardless of cardiac volume. These goals appear to be best achieved with on-pump CABG, which remains the gold standard."

Dr. Bakaeen reported having no financial disclosures.

Dr. Lazar reported that he receives grants and research support from Eli Lilly.

TORONTO – In the United States, fewer than one in five coronary artery bypass graft surgeries are done without cardiopulmonary bypass, according to a large Society of Thoracic Surgeons database study conducted by Dr. Faisal G. Bakaeen of Baylor College of Medicine, the Michael E. DeBakey VA Medical Center, and the Texas Heart Institute, Houston, and colleagues.

As of 2012, 84% of the centers in the United States were doing either 0 or fewer than 50 off-pump cases per year. Among U.S. surgeons, 86% did either no off-pump coronary artery bypass grafts (CABG) or 20 or fewer cases per year.

"We speculate that this decline is because off-pump is technically a more demanding operation than on-pump," said Dr. Bakaeen during his presentation at the annual meeting of the American Association of Thoracic Surgery.

"There are [also] concerns about graft patency and the completeness of revascularization and randomized, controlled trials have shown no mortality or major – and I emphasize major – morbidity benefit."

The invited discussant for the abstract, Dr. Harold L. Lazar, the director of cardiothoracic surgery research at Boston Medical Center, suggested that off-pump CABG numbers "will continue to decline" as overall CABG volume continues to decline, and as higher-volume centers and surgeons opt to do fewer off-pump cases.

"Cardiac surgeons have always been motivated to adopt new techniques that will result in improved outcomes for their patients," said Dr. Lazar. "The continuing decline in the use of OP-CABG [off-pump CABG ] by U.S. surgeons is an indication that OP-CABG is not this type of technique."

Introduced in the early 1990s, off-pump CABG was initially touted as a means of avoiding several of the adverse effects of cardiopulmonary bypass and aortic manipulation. However, the relative benefits of off-pump as compared to on-pump CABG continue to be hotly debated.

Dr. Bakaeen and colleagues used the Society of Thoracic Surgeons Adult Cardiac Surgery Database to examine national trends in the use of off- versus on-pump CABG, looking specifically at volume-specific trends among centers and surgeons.

"This is a megadatabase with a huge number of patients, over 2.1 million patients and over 1,200 centers," said Dr. Bakaeen.

The off-pump and on-pump CABG percentages were calculated in aggregate, by center, and by surgeon for a total of 2,137,841 isolated primary CABG procedures performed between Jan. 1, 1997 and Sept. 30, 2012.

Based on 2007/2008 yearly off-pump volume, the analysis subgroups were "high" [center number greater than 200 cases, surgeon number greater than 100 cases], "intermediate" [center number equals 50-200, surgeon number equals 20-100], and "low" [center number less than 50, surgeon number less than 20].

The utilization of off-pump peaked in 2002 at about 23% but then decreased to 17% in 2012. Most of this decrease was found to be driven by higher-volume centers and higher-volume surgeons doing fewer off-pump cases.

Indeed, for the most recent years studied (2011-2012), 12% of U.S. centers (1,056) and 34% of U.S. surgeons (2,626) did not do any off-pump CABG cases.

Another 72% of centers and 52% of surgeons were low-volume operators (less than 50 cases/year and less than 20 cases/year, respectively.

Only 1% of centers (150) and 1% of surgeons (38) were classified as high-volume off-pump operators.

Of note, while the overall conversion rate – cases that were started as on- or off-pump and switched midprocedure – has remained fairly steady at 6%, the rate of unplanned conversions has risen from a low of about 1% in 2004 to about 3.2% in 2012.

"What was interesting was that there was a direct correlation between off-pump volume and the experience of the surgeon and the conversion rate," reported Dr. Bakaeen.

"So, if you are a higher-volume, experienced off-pump surgeon, you are three times less likely to convert than a low-volume surgeon [P less than .01]."

Dr. Bakaeen concluded that, "off-pump CABG utilization will likely continue to be concentrated in specialized centers and performed by dedicated off-pump surgeons."

Dr. Lazar added: "No operation that can only be performed by a select group of experienced, talented surgeons has ever achieved the test of time. CABG surgery must be performed expertly under all circumstances in all patients and at all hospitals, regardless of cardiac volume. These goals appear to be best achieved with on-pump CABG, which remains the gold standard."

Dr. Bakaeen reported having no financial disclosures.

Dr. Lazar reported that he receives grants and research support from Eli Lilly.

TORONTO – In the United States, fewer than one in five coronary artery bypass graft surgeries are done without cardiopulmonary bypass, according to a large Society of Thoracic Surgeons database study conducted by Dr. Faisal G. Bakaeen of Baylor College of Medicine, the Michael E. DeBakey VA Medical Center, and the Texas Heart Institute, Houston, and colleagues.

As of 2012, 84% of the centers in the United States were doing either 0 or fewer than 50 off-pump cases per year. Among U.S. surgeons, 86% did either no off-pump coronary artery bypass grafts (CABG) or 20 or fewer cases per year.

"We speculate that this decline is because off-pump is technically a more demanding operation than on-pump," said Dr. Bakaeen during his presentation at the annual meeting of the American Association of Thoracic Surgery.

"There are [also] concerns about graft patency and the completeness of revascularization and randomized, controlled trials have shown no mortality or major – and I emphasize major – morbidity benefit."

The invited discussant for the abstract, Dr. Harold L. Lazar, the director of cardiothoracic surgery research at Boston Medical Center, suggested that off-pump CABG numbers "will continue to decline" as overall CABG volume continues to decline, and as higher-volume centers and surgeons opt to do fewer off-pump cases.

"Cardiac surgeons have always been motivated to adopt new techniques that will result in improved outcomes for their patients," said Dr. Lazar. "The continuing decline in the use of OP-CABG [off-pump CABG ] by U.S. surgeons is an indication that OP-CABG is not this type of technique."

Introduced in the early 1990s, off-pump CABG was initially touted as a means of avoiding several of the adverse effects of cardiopulmonary bypass and aortic manipulation. However, the relative benefits of off-pump as compared to on-pump CABG continue to be hotly debated.

Dr. Bakaeen and colleagues used the Society of Thoracic Surgeons Adult Cardiac Surgery Database to examine national trends in the use of off- versus on-pump CABG, looking specifically at volume-specific trends among centers and surgeons.

"This is a megadatabase with a huge number of patients, over 2.1 million patients and over 1,200 centers," said Dr. Bakaeen.

The off-pump and on-pump CABG percentages were calculated in aggregate, by center, and by surgeon for a total of 2,137,841 isolated primary CABG procedures performed between Jan. 1, 1997 and Sept. 30, 2012.

Based on 2007/2008 yearly off-pump volume, the analysis subgroups were "high" [center number greater than 200 cases, surgeon number greater than 100 cases], "intermediate" [center number equals 50-200, surgeon number equals 20-100], and "low" [center number less than 50, surgeon number less than 20].

The utilization of off-pump peaked in 2002 at about 23% but then decreased to 17% in 2012. Most of this decrease was found to be driven by higher-volume centers and higher-volume surgeons doing fewer off-pump cases.

Indeed, for the most recent years studied (2011-2012), 12% of U.S. centers (1,056) and 34% of U.S. surgeons (2,626) did not do any off-pump CABG cases.

Another 72% of centers and 52% of surgeons were low-volume operators (less than 50 cases/year and less than 20 cases/year, respectively.

Only 1% of centers (150) and 1% of surgeons (38) were classified as high-volume off-pump operators.

Of note, while the overall conversion rate – cases that were started as on- or off-pump and switched midprocedure – has remained fairly steady at 6%, the rate of unplanned conversions has risen from a low of about 1% in 2004 to about 3.2% in 2012.

"What was interesting was that there was a direct correlation between off-pump volume and the experience of the surgeon and the conversion rate," reported Dr. Bakaeen.

"So, if you are a higher-volume, experienced off-pump surgeon, you are three times less likely to convert than a low-volume surgeon [P less than .01]."

Dr. Bakaeen concluded that, "off-pump CABG utilization will likely continue to be concentrated in specialized centers and performed by dedicated off-pump surgeons."

Dr. Lazar added: "No operation that can only be performed by a select group of experienced, talented surgeons has ever achieved the test of time. CABG surgery must be performed expertly under all circumstances in all patients and at all hospitals, regardless of cardiac volume. These goals appear to be best achieved with on-pump CABG, which remains the gold standard."

Dr. Bakaeen reported having no financial disclosures.

Dr. Lazar reported that he receives grants and research support from Eli Lilly.

TORONTO – Mitral valve repair rates continue to show great variability, ranging from 0% to 90% for patients with moderate to severe mitral regurgitation, according to data presented by Dr. Damien J. LaPar, a thoracic surgeon at the University of Virginia, Charlottesville.

Surgeons performing more than 20 mitral cases per year were about three times more likely to perform a repair over a replacement compared with surgeons performing fewer than 20 mitral surgeries per year.

"Average annual surgeon volume appears more significantly associated with an increased likelihood for mitral repair than institutional volume," Dr. LaPar reported at the annual meeting of the American Association for Thoracic Surgery. A video of his live presentation is available at the AATS website.

Mitral valve repair appears to be underused despite accumulated data favoring repair over replacement in the treatment of patients with moderate to severe mitral regurgitation. Dr. LaPar and colleagues evaluated the relationship between procedure volume and propensity for mitral repair (over replacement) in a multi-institution cohort of patients.

The Virginia Cardiac Surgery Quality Initiative is a voluntary consortium of 17 collaborating cardiac surgery centers in Virginia that captures about 99% of all the operations performed in the state, with each center contributing their data to the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database.

Records for 4,178 patients were evaluated for 2001-2012; 2,516 of these patients underwent isolated mitral valve replacement and 1,662 underwent isolated mitral valve repair. To examine confounding, a propensity-matched cohort was developed with 1,661 patients in each group.

Median annual mitral procedure volume was 54 cases per year for hospitals, ranging from 5 to 128, and 13 cases per year for individual surgeons, ranging from 0 to 58 cases. Mitral valve repair rates also ranged significantly, from 35% to 70% of all mitral valve procedures for hospitals and from 0% to 90% for surgeons.

Mitral valve replacement patients presented with higher STS PROM (5.6% vs. 1.7%, P less than .001), higher age, and a greater number of comorbidities. When the researchers adjusted for STS PROM, both average annual hospital (P = .04) and surgeon (P less than .0001) mitral procedure volumes were associated with probability of mitral repair, with surgeon volume showing more influence in the decision to repair rather than replace the mitral valve.

When the propensity to perform mitral valve repair was plotted against surgeon volume, there was a clear "inflection point" of increased probability for repair over replacement when the average annual surgeon mitral volume (a surrogate for surgeon experience) exceeded 20 operations yearly. This finding was validated in the propensity-matched cohort.

"We did a post hoc analysis and demonstrated that when you categorize volume by our visible threshold of 20 cases per year, for both hospital and surgeon volume in the overall cohort, hospitals and surgeons performing more than 20 cases per year, more strongly performed mitral valve repair," said Dr. LaPar.

Indeed, among surgeons and hospitals performing more than 20 mitral operations annually, repairs were done in 62% of cases, compared to 37% for lower-volume centers. Among surgeons performing more than 20 mitral cases per year, repair rates were 73% compared to 26% for lower-volume mitral operators (both P less than .001).

Similarly significant differences were seen in the propensity-matched cohort, although the effect was more muted (53% vs. 47% for high- and low-volume hospitals and 67% vs. 39% for high- and low-volume surgeons; P less than .001 for both).

"In the upcoming era of percutaneous mitral valve repair technology, we believe that surgeon volume and expertise should act as a gatekeeper and should dictate not only access to this technology but the role of surgeons and cardiologists in this," concluded Dr. LaPar.

"This will be an excellent contribution to the literature further defining the relationship between surgeon volume and hospital center volume in mitral valve surgical outcomes and choice of operation," said the invited discussant, Dr. David A Fullerton of the University of Colorado at Denver, Aurora.

Dr. Daniel Drake, head of the Michigan Society of Thoracic and Cardiovascular Surgeons Mitral Initiative, added that in his state they have started to see a greater number of referrals – based on an assessment of case complexity – from less experienced surgeons to more experienced surgeons. Dr. LaPar noted that he hadn’t yet seen this widely in Virginia.

Dr. LaPar and Dr. Fullerton reported no disclosures.

TORONTO – Mitral valve repair rates continue to show great variability, ranging from 0% to 90% for patients with moderate to severe mitral regurgitation, according to data presented by Dr. Damien J. LaPar, a thoracic surgeon at the University of Virginia, Charlottesville.

Surgeons performing more than 20 mitral cases per year were about three times more likely to perform a repair over a replacement compared with surgeons performing fewer than 20 mitral surgeries per year.

"Average annual surgeon volume appears more significantly associated with an increased likelihood for mitral repair than institutional volume," Dr. LaPar reported at the annual meeting of the American Association for Thoracic Surgery. A video of his live presentation is available at the AATS website.

Mitral valve repair appears to be underused despite accumulated data favoring repair over replacement in the treatment of patients with moderate to severe mitral regurgitation. Dr. LaPar and colleagues evaluated the relationship between procedure volume and propensity for mitral repair (over replacement) in a multi-institution cohort of patients.

The Virginia Cardiac Surgery Quality Initiative is a voluntary consortium of 17 collaborating cardiac surgery centers in Virginia that captures about 99% of all the operations performed in the state, with each center contributing their data to the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database.

Records for 4,178 patients were evaluated for 2001-2012; 2,516 of these patients underwent isolated mitral valve replacement and 1,662 underwent isolated mitral valve repair. To examine confounding, a propensity-matched cohort was developed with 1,661 patients in each group.

Median annual mitral procedure volume was 54 cases per year for hospitals, ranging from 5 to 128, and 13 cases per year for individual surgeons, ranging from 0 to 58 cases. Mitral valve repair rates also ranged significantly, from 35% to 70% of all mitral valve procedures for hospitals and from 0% to 90% for surgeons.

Mitral valve replacement patients presented with higher STS PROM (5.6% vs. 1.7%, P less than .001), higher age, and a greater number of comorbidities. When the researchers adjusted for STS PROM, both average annual hospital (P = .04) and surgeon (P less than .0001) mitral procedure volumes were associated with probability of mitral repair, with surgeon volume showing more influence in the decision to repair rather than replace the mitral valve.

When the propensity to perform mitral valve repair was plotted against surgeon volume, there was a clear "inflection point" of increased probability for repair over replacement when the average annual surgeon mitral volume (a surrogate for surgeon experience) exceeded 20 operations yearly. This finding was validated in the propensity-matched cohort.

"We did a post hoc analysis and demonstrated that when you categorize volume by our visible threshold of 20 cases per year, for both hospital and surgeon volume in the overall cohort, hospitals and surgeons performing more than 20 cases per year, more strongly performed mitral valve repair," said Dr. LaPar.

Indeed, among surgeons and hospitals performing more than 20 mitral operations annually, repairs were done in 62% of cases, compared to 37% for lower-volume centers. Among surgeons performing more than 20 mitral cases per year, repair rates were 73% compared to 26% for lower-volume mitral operators (both P less than .001).

Similarly significant differences were seen in the propensity-matched cohort, although the effect was more muted (53% vs. 47% for high- and low-volume hospitals and 67% vs. 39% for high- and low-volume surgeons; P less than .001 for both).

"In the upcoming era of percutaneous mitral valve repair technology, we believe that surgeon volume and expertise should act as a gatekeeper and should dictate not only access to this technology but the role of surgeons and cardiologists in this," concluded Dr. LaPar.

"This will be an excellent contribution to the literature further defining the relationship between surgeon volume and hospital center volume in mitral valve surgical outcomes and choice of operation," said the invited discussant, Dr. David A Fullerton of the University of Colorado at Denver, Aurora.

Dr. Daniel Drake, head of the Michigan Society of Thoracic and Cardiovascular Surgeons Mitral Initiative, added that in his state they have started to see a greater number of referrals – based on an assessment of case complexity – from less experienced surgeons to more experienced surgeons. Dr. LaPar noted that he hadn’t yet seen this widely in Virginia.

Dr. LaPar and Dr. Fullerton reported no disclosures.

TORONTO – Mitral valve repair rates continue to show great variability, ranging from 0% to 90% for patients with moderate to severe mitral regurgitation, according to data presented by Dr. Damien J. LaPar, a thoracic surgeon at the University of Virginia, Charlottesville.

Surgeons performing more than 20 mitral cases per year were about three times more likely to perform a repair over a replacement compared with surgeons performing fewer than 20 mitral surgeries per year.

"Average annual surgeon volume appears more significantly associated with an increased likelihood for mitral repair than institutional volume," Dr. LaPar reported at the annual meeting of the American Association for Thoracic Surgery. A video of his live presentation is available at the AATS website.

Mitral valve repair appears to be underused despite accumulated data favoring repair over replacement in the treatment of patients with moderate to severe mitral regurgitation. Dr. LaPar and colleagues evaluated the relationship between procedure volume and propensity for mitral repair (over replacement) in a multi-institution cohort of patients.

The Virginia Cardiac Surgery Quality Initiative is a voluntary consortium of 17 collaborating cardiac surgery centers in Virginia that captures about 99% of all the operations performed in the state, with each center contributing their data to the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database.

Records for 4,178 patients were evaluated for 2001-2012; 2,516 of these patients underwent isolated mitral valve replacement and 1,662 underwent isolated mitral valve repair. To examine confounding, a propensity-matched cohort was developed with 1,661 patients in each group.

Median annual mitral procedure volume was 54 cases per year for hospitals, ranging from 5 to 128, and 13 cases per year for individual surgeons, ranging from 0 to 58 cases. Mitral valve repair rates also ranged significantly, from 35% to 70% of all mitral valve procedures for hospitals and from 0% to 90% for surgeons.

Mitral valve replacement patients presented with higher STS PROM (5.6% vs. 1.7%, P less than .001), higher age, and a greater number of comorbidities. When the researchers adjusted for STS PROM, both average annual hospital (P = .04) and surgeon (P less than .0001) mitral procedure volumes were associated with probability of mitral repair, with surgeon volume showing more influence in the decision to repair rather than replace the mitral valve.

When the propensity to perform mitral valve repair was plotted against surgeon volume, there was a clear "inflection point" of increased probability for repair over replacement when the average annual surgeon mitral volume (a surrogate for surgeon experience) exceeded 20 operations yearly. This finding was validated in the propensity-matched cohort.

"We did a post hoc analysis and demonstrated that when you categorize volume by our visible threshold of 20 cases per year, for both hospital and surgeon volume in the overall cohort, hospitals and surgeons performing more than 20 cases per year, more strongly performed mitral valve repair," said Dr. LaPar.

Indeed, among surgeons and hospitals performing more than 20 mitral operations annually, repairs were done in 62% of cases, compared to 37% for lower-volume centers. Among surgeons performing more than 20 mitral cases per year, repair rates were 73% compared to 26% for lower-volume mitral operators (both P less than .001).

Similarly significant differences were seen in the propensity-matched cohort, although the effect was more muted (53% vs. 47% for high- and low-volume hospitals and 67% vs. 39% for high- and low-volume surgeons; P less than .001 for both).

"In the upcoming era of percutaneous mitral valve repair technology, we believe that surgeon volume and expertise should act as a gatekeeper and should dictate not only access to this technology but the role of surgeons and cardiologists in this," concluded Dr. LaPar.

"This will be an excellent contribution to the literature further defining the relationship between surgeon volume and hospital center volume in mitral valve surgical outcomes and choice of operation," said the invited discussant, Dr. David A Fullerton of the University of Colorado at Denver, Aurora.

Dr. Daniel Drake, head of the Michigan Society of Thoracic and Cardiovascular Surgeons Mitral Initiative, added that in his state they have started to see a greater number of referrals – based on an assessment of case complexity – from less experienced surgeons to more experienced surgeons. Dr. LaPar noted that he hadn’t yet seen this widely in Virginia.

Dr. LaPar and Dr. Fullerton reported no disclosures.

TORONTO – In a multicenter European study, 30-day mortality and 1-year mortality after implantation of the stentless Freedom Solo aortic bioprosthetic valve were 1.4% and 4.4%, respectively. Patients in the study experienced "remarkable" functional status improvement at 1 year, reported principal investigator Dr. Markus Thalmann at the annual meeting of the American Association for Thoracic Surgery.

"Our trial showed excellent results in terms of morbidity and mortality and low rates of valve-related adverse events in a 12-month follow-up period," said Dr. Thalmann during his late-breaking clinical trials presentation. "It also demonstrated good hemodynamics leading to a remarkable functional status improvement."

The Sorin Freedom Solo aortic bioprosthesis is made of two layers of bovine pericardium, with no synthetic material added. The valve is implanted with a single running suture line technique in a strict supra-annular position and has no contact with the native annulus. The bioprosthesis is not approved in the United States.

Dr. Thalmann, of Krankenhaus Hietzing, Vienna, noted the importance of performing a careful decalcification of the annulus during implantation. "You should do it as properly as you’d do it when implanting a stented valve, even if you don’t put your stitches through the annulus," he said.

In response to a question, he said that the trial was requested by the Food and Drug Administration to provide more information on the single-line suture technique used to implant the valve.

The researchers conducted a prospective, nonrandomized, multicenter trial at 18 clinical centers in eight European countries. All patients with an indication for prosthetic aortic valve replacement were included, except those with a preexisting valve prosthesis in the mitral, pulmonary, or tricuspid positions. Patients needing double or triple valve replacement were also excluded, as were those with active endocarditis and congenital bicuspid valves.

A total of 616 patients received the valve. Patients had a mean age of 74.5 years, 45.9% were female, and the mean logistic EuroSCORE was 10.1%. Concomitant cardiac procedures, including coronary artery bypass grafting, were performed in 43.2% of patients.

Early (30-day) mortality was 1.4%, rising to 4.4% at 1 year. Valve-related mortality at 30 days and 1 year was 0.3% and 1.1%, respectively.

Overall morbidity was low. At 30 days, 4.5% of patients required reintervention for bleeding, 0.3% for perivalvular leakage. No structural valve dysfunction or valve thrombosis was noted at 30 days, with one case of each seen at 1 year (0.2% and 0.2%).

Preoperatively, 49.3% of patients were in New York Heart Association class III or IV heart failure. At 1 year, 97.0% were in NYHA class I or II heart failure.

"We found good hemodynamics after 1 year," said Dr. Thalmann. The overall mean gradient was 7.2 mm Hg, and the effective orifice area was 1.5 cm².

Patients will be followed for up to 5 years.

The Freedom Solo valve is currently being tested in an investigational device exemption (IDE) study in the United States. The Sorin Solo Smart valve, the evolution of the Freedom Solo valve, received a European CE mark approval in November 2013.

Dr. Thalmann is a consultant for the Sorin Group, which funded the study.

TORONTO – In a multicenter European study, 30-day mortality and 1-year mortality after implantation of the stentless Freedom Solo aortic bioprosthetic valve were 1.4% and 4.4%, respectively. Patients in the study experienced "remarkable" functional status improvement at 1 year, reported principal investigator Dr. Markus Thalmann at the annual meeting of the American Association for Thoracic Surgery.

"Our trial showed excellent results in terms of morbidity and mortality and low rates of valve-related adverse events in a 12-month follow-up period," said Dr. Thalmann during his late-breaking clinical trials presentation. "It also demonstrated good hemodynamics leading to a remarkable functional status improvement."

The Sorin Freedom Solo aortic bioprosthesis is made of two layers of bovine pericardium, with no synthetic material added. The valve is implanted with a single running suture line technique in a strict supra-annular position and has no contact with the native annulus. The bioprosthesis is not approved in the United States.

Dr. Thalmann, of Krankenhaus Hietzing, Vienna, noted the importance of performing a careful decalcification of the annulus during implantation. "You should do it as properly as you’d do it when implanting a stented valve, even if you don’t put your stitches through the annulus," he said.

In response to a question, he said that the trial was requested by the Food and Drug Administration to provide more information on the single-line suture technique used to implant the valve.

The researchers conducted a prospective, nonrandomized, multicenter trial at 18 clinical centers in eight European countries. All patients with an indication for prosthetic aortic valve replacement were included, except those with a preexisting valve prosthesis in the mitral, pulmonary, or tricuspid positions. Patients needing double or triple valve replacement were also excluded, as were those with active endocarditis and congenital bicuspid valves.

A total of 616 patients received the valve. Patients had a mean age of 74.5 years, 45.9% were female, and the mean logistic EuroSCORE was 10.1%. Concomitant cardiac procedures, including coronary artery bypass grafting, were performed in 43.2% of patients.

Early (30-day) mortality was 1.4%, rising to 4.4% at 1 year. Valve-related mortality at 30 days and 1 year was 0.3% and 1.1%, respectively.

Overall morbidity was low. At 30 days, 4.5% of patients required reintervention for bleeding, 0.3% for perivalvular leakage. No structural valve dysfunction or valve thrombosis was noted at 30 days, with one case of each seen at 1 year (0.2% and 0.2%).

Preoperatively, 49.3% of patients were in New York Heart Association class III or IV heart failure. At 1 year, 97.0% were in NYHA class I or II heart failure.

"We found good hemodynamics after 1 year," said Dr. Thalmann. The overall mean gradient was 7.2 mm Hg, and the effective orifice area was 1.5 cm².

Patients will be followed for up to 5 years.

The Freedom Solo valve is currently being tested in an investigational device exemption (IDE) study in the United States. The Sorin Solo Smart valve, the evolution of the Freedom Solo valve, received a European CE mark approval in November 2013.

Dr. Thalmann is a consultant for the Sorin Group, which funded the study.

TORONTO – In a multicenter European study, 30-day mortality and 1-year mortality after implantation of the stentless Freedom Solo aortic bioprosthetic valve were 1.4% and 4.4%, respectively. Patients in the study experienced "remarkable" functional status improvement at 1 year, reported principal investigator Dr. Markus Thalmann at the annual meeting of the American Association for Thoracic Surgery.

"Our trial showed excellent results in terms of morbidity and mortality and low rates of valve-related adverse events in a 12-month follow-up period," said Dr. Thalmann during his late-breaking clinical trials presentation. "It also demonstrated good hemodynamics leading to a remarkable functional status improvement."

The Sorin Freedom Solo aortic bioprosthesis is made of two layers of bovine pericardium, with no synthetic material added. The valve is implanted with a single running suture line technique in a strict supra-annular position and has no contact with the native annulus. The bioprosthesis is not approved in the United States.

Dr. Thalmann, of Krankenhaus Hietzing, Vienna, noted the importance of performing a careful decalcification of the annulus during implantation. "You should do it as properly as you’d do it when implanting a stented valve, even if you don’t put your stitches through the annulus," he said.

In response to a question, he said that the trial was requested by the Food and Drug Administration to provide more information on the single-line suture technique used to implant the valve.

The researchers conducted a prospective, nonrandomized, multicenter trial at 18 clinical centers in eight European countries. All patients with an indication for prosthetic aortic valve replacement were included, except those with a preexisting valve prosthesis in the mitral, pulmonary, or tricuspid positions. Patients needing double or triple valve replacement were also excluded, as were those with active endocarditis and congenital bicuspid valves.

A total of 616 patients received the valve. Patients had a mean age of 74.5 years, 45.9% were female, and the mean logistic EuroSCORE was 10.1%. Concomitant cardiac procedures, including coronary artery bypass grafting, were performed in 43.2% of patients.

Early (30-day) mortality was 1.4%, rising to 4.4% at 1 year. Valve-related mortality at 30 days and 1 year was 0.3% and 1.1%, respectively.

Overall morbidity was low. At 30 days, 4.5% of patients required reintervention for bleeding, 0.3% for perivalvular leakage. No structural valve dysfunction or valve thrombosis was noted at 30 days, with one case of each seen at 1 year (0.2% and 0.2%).

Preoperatively, 49.3% of patients were in New York Heart Association class III or IV heart failure. At 1 year, 97.0% were in NYHA class I or II heart failure.

"We found good hemodynamics after 1 year," said Dr. Thalmann. The overall mean gradient was 7.2 mm Hg, and the effective orifice area was 1.5 cm².

Patients will be followed for up to 5 years.

The Freedom Solo valve is currently being tested in an investigational device exemption (IDE) study in the United States. The Sorin Solo Smart valve, the evolution of the Freedom Solo valve, received a European CE mark approval in November 2013.

Dr. Thalmann is a consultant for the Sorin Group, which funded the study.

TORONTO – Device positioning may help explain significant increases in pump thrombosis after left ventricular assist device implantation, according to a single-center study presented at the 2014 annual meeting of the American Association for Thoracic Surgery.

Dr. Jay Bhama, associate director of lung and heart transplantation at the University of Pittsburgh, found that more device-positioning issues coincided with more occurrences of pump thrombosis (PT). The adequacy of anticoagulation, major adverse events, and medical noncompliance were not found to be contributing factors, Dr. Bhama said.

His investigation joins recently published data indicating that left ventricular assist device (LVAD) thrombosis nearly quadrupled in less than 2 years in a multicenter study.

The purported mechanisms of PT in patients supported with the HeartMate II LVAD are thought to be multifactorial, but possibly related to design modifications, expansion of use to the destination therapy indication, nonuniform surgical implant technique, and nonuniform anticoagulation strategies across centers and over time.

"Starting in 2010, we started to notice a rapid and sudden increase in the rate of pump thrombosis, which has increased steadily over the last 3 years," said Dr. Bhama, who reported that PT occurred in 10 of 62 patients (16%) treated at the University of Pittsburgh Medical Center, with an overall event rate of 0.281 per patient-year.

In response to the increase, the group at the medical center investigated how potential contributing factors may have changed over time. They retrospectively assessed all primary LVAD implants in patients who survived hospitalization (62 of 74 total implants) between 2004 and 2012, grouping patients according to the era of implant: from June 2004 to December 2009 (era 1; n = 24) and from January 2010 (when FDA approval was given to expand use to destination therapy) to December 2012 (era 2; n = 38).

None of those who died during the index hospitalization experienced PT, Dr. Bhama noted.

PT was defined as either visualized thrombus within the pump at device exchange or significant hemolysis in the setting of heart failure symptoms or pump malfunction.

The actuarial freedom from PT at 24 months was significantly lower in era 2 than in era 1 (57% vs. 100%; P = .016).

Effective anticoagulation (percent of all international normalized ratio [INR] measurements greater than 1.8) was more reliably achieved in era 2 than in era 1 (50% vs. 34%; P less than .001).

To assess device positioning, the researchers looked at the angle of the inflow cannula, defining malposition as either less than the 5th or greater than the 95th percentile of the median of all the inflow cannula angles. Regarding the outflow cannula, they looked at patients who had bend-relief disconnects, either partial or complete, and those who had radiographic evidence of outflow graft malposition or kink.

Device positioning issues were significantly more prevalent during era 2 than during era 1 (29% vs. 4%). Most of this difference was driven by inflow cannula positioning problems, Dr. Bhama noted.

When the patients with concerns related to device positioning were excluded, the freedom from PT at 24 months no longer differed significantly between groups (P = .094).

The groups were demographically similar except for age, which was higher in the era 2 group (57 years, vs. 50 years for era 1; P = .037). More patients in the era 2 group received an LVAD for destination therapy, although this difference actually wasn’t significant (61% vs. 38%; P = .066).

The groups were also similar with regard to early major adverse events (right ventricular failure, bleeding, infection, and stroke) and medical noncompliance.

In the earlier multicenter study, Dr. Randall C. Starling, of the Cleveland Clinic, and his colleagues reported an abrupt increase in LVAD thrombosis: Between March 2011 and Jan. 1, 2013, the occurrence of PT at 3 months after implantation increased from 2.2% to 8.4% (N. Engl. J. Med. 2014;370:33-40).

"Dissecting the root cause of this problem is an extremely difficult task," said Dr. Nader Moazami, the invited discussant for Dr. Bhama’s presentation and the second author on the Starling paper. Dr. Moazami is surgical director of the Kaufman Center for Heart Failure at the Cleveland Clinic.

"While recent advances in LVAD technology with continuous-flow pumps have saved the lives of thousands of dying patients, issues related to adverse events and the associated morbidity and mortality are of immense importance, specifically as we consider the relevance of this technology to the more ambulatory heart failure patients," said Dr. Moazami, commenting on the study.

However, he suggested that the real cause of the recent increase in PT has not yet been discovered, and questioned the validity of assessing inflow cannula angulation based on a chest x-ray. "This to my knowledge has never been validated and was a concern in about half of the patients in the pump thrombosis group," Dr. Moazami said. Patients with "a demonstrable mechanical reason for pump thrombosis" were excluded from the Starling team’s analysis, he added.

In response, Dr. Bhama cited a study by Dr. Abeel Mangi, a cardiac surgeon at Yale University, New Haven, Conn., which found that greater angulation of the HeartMate II inflow cannula, along with the depth of the pump pocket, correlated with the development of PT (Ann. Thorac. Surg. 2013;96:1259-65).

"These aren’t just angles that are slightly off here and there," noted Dr. Bhama. "These are splayed very widely, situations I think where we all would say this is something we should be concerned about."

Dr. Bhama reported no relevant disclosures.

TORONTO – Device positioning may help explain significant increases in pump thrombosis after left ventricular assist device implantation, according to a single-center study presented at the 2014 annual meeting of the American Association for Thoracic Surgery.

Dr. Jay Bhama, associate director of lung and heart transplantation at the University of Pittsburgh, found that more device-positioning issues coincided with more occurrences of pump thrombosis (PT). The adequacy of anticoagulation, major adverse events, and medical noncompliance were not found to be contributing factors, Dr. Bhama said.

His investigation joins recently published data indicating that left ventricular assist device (LVAD) thrombosis nearly quadrupled in less than 2 years in a multicenter study.

The purported mechanisms of PT in patients supported with the HeartMate II LVAD are thought to be multifactorial, but possibly related to design modifications, expansion of use to the destination therapy indication, nonuniform surgical implant technique, and nonuniform anticoagulation strategies across centers and over time.

"Starting in 2010, we started to notice a rapid and sudden increase in the rate of pump thrombosis, which has increased steadily over the last 3 years," said Dr. Bhama, who reported that PT occurred in 10 of 62 patients (16%) treated at the University of Pittsburgh Medical Center, with an overall event rate of 0.281 per patient-year.

In response to the increase, the group at the medical center investigated how potential contributing factors may have changed over time. They retrospectively assessed all primary LVAD implants in patients who survived hospitalization (62 of 74 total implants) between 2004 and 2012, grouping patients according to the era of implant: from June 2004 to December 2009 (era 1; n = 24) and from January 2010 (when FDA approval was given to expand use to destination therapy) to December 2012 (era 2; n = 38).

None of those who died during the index hospitalization experienced PT, Dr. Bhama noted.

PT was defined as either visualized thrombus within the pump at device exchange or significant hemolysis in the setting of heart failure symptoms or pump malfunction.

The actuarial freedom from PT at 24 months was significantly lower in era 2 than in era 1 (57% vs. 100%; P = .016).

Effective anticoagulation (percent of all international normalized ratio [INR] measurements greater than 1.8) was more reliably achieved in era 2 than in era 1 (50% vs. 34%; P less than .001).

To assess device positioning, the researchers looked at the angle of the inflow cannula, defining malposition as either less than the 5th or greater than the 95th percentile of the median of all the inflow cannula angles. Regarding the outflow cannula, they looked at patients who had bend-relief disconnects, either partial or complete, and those who had radiographic evidence of outflow graft malposition or kink.

Device positioning issues were significantly more prevalent during era 2 than during era 1 (29% vs. 4%). Most of this difference was driven by inflow cannula positioning problems, Dr. Bhama noted.

When the patients with concerns related to device positioning were excluded, the freedom from PT at 24 months no longer differed significantly between groups (P = .094).

The groups were demographically similar except for age, which was higher in the era 2 group (57 years, vs. 50 years for era 1; P = .037). More patients in the era 2 group received an LVAD for destination therapy, although this difference actually wasn’t significant (61% vs. 38%; P = .066).

The groups were also similar with regard to early major adverse events (right ventricular failure, bleeding, infection, and stroke) and medical noncompliance.

In the earlier multicenter study, Dr. Randall C. Starling, of the Cleveland Clinic, and his colleagues reported an abrupt increase in LVAD thrombosis: Between March 2011 and Jan. 1, 2013, the occurrence of PT at 3 months after implantation increased from 2.2% to 8.4% (N. Engl. J. Med. 2014;370:33-40).

"Dissecting the root cause of this problem is an extremely difficult task," said Dr. Nader Moazami, the invited discussant for Dr. Bhama’s presentation and the second author on the Starling paper. Dr. Moazami is surgical director of the Kaufman Center for Heart Failure at the Cleveland Clinic.

"While recent advances in LVAD technology with continuous-flow pumps have saved the lives of thousands of dying patients, issues related to adverse events and the associated morbidity and mortality are of immense importance, specifically as we consider the relevance of this technology to the more ambulatory heart failure patients," said Dr. Moazami, commenting on the study.

However, he suggested that the real cause of the recent increase in PT has not yet been discovered, and questioned the validity of assessing inflow cannula angulation based on a chest x-ray. "This to my knowledge has never been validated and was a concern in about half of the patients in the pump thrombosis group," Dr. Moazami said. Patients with "a demonstrable mechanical reason for pump thrombosis" were excluded from the Starling team’s analysis, he added.

In response, Dr. Bhama cited a study by Dr. Abeel Mangi, a cardiac surgeon at Yale University, New Haven, Conn., which found that greater angulation of the HeartMate II inflow cannula, along with the depth of the pump pocket, correlated with the development of PT (Ann. Thorac. Surg. 2013;96:1259-65).

"These aren’t just angles that are slightly off here and there," noted Dr. Bhama. "These are splayed very widely, situations I think where we all would say this is something we should be concerned about."

Dr. Bhama reported no relevant disclosures.

TORONTO – Device positioning may help explain significant increases in pump thrombosis after left ventricular assist device implantation, according to a single-center study presented at the 2014 annual meeting of the American Association for Thoracic Surgery.

Dr. Jay Bhama, associate director of lung and heart transplantation at the University of Pittsburgh, found that more device-positioning issues coincided with more occurrences of pump thrombosis (PT). The adequacy of anticoagulation, major adverse events, and medical noncompliance were not found to be contributing factors, Dr. Bhama said.

His investigation joins recently published data indicating that left ventricular assist device (LVAD) thrombosis nearly quadrupled in less than 2 years in a multicenter study.

The purported mechanisms of PT in patients supported with the HeartMate II LVAD are thought to be multifactorial, but possibly related to design modifications, expansion of use to the destination therapy indication, nonuniform surgical implant technique, and nonuniform anticoagulation strategies across centers and over time.

"Starting in 2010, we started to notice a rapid and sudden increase in the rate of pump thrombosis, which has increased steadily over the last 3 years," said Dr. Bhama, who reported that PT occurred in 10 of 62 patients (16%) treated at the University of Pittsburgh Medical Center, with an overall event rate of 0.281 per patient-year.

In response to the increase, the group at the medical center investigated how potential contributing factors may have changed over time. They retrospectively assessed all primary LVAD implants in patients who survived hospitalization (62 of 74 total implants) between 2004 and 2012, grouping patients according to the era of implant: from June 2004 to December 2009 (era 1; n = 24) and from January 2010 (when FDA approval was given to expand use to destination therapy) to December 2012 (era 2; n = 38).

None of those who died during the index hospitalization experienced PT, Dr. Bhama noted.

PT was defined as either visualized thrombus within the pump at device exchange or significant hemolysis in the setting of heart failure symptoms or pump malfunction.

The actuarial freedom from PT at 24 months was significantly lower in era 2 than in era 1 (57% vs. 100%; P = .016).

Effective anticoagulation (percent of all international normalized ratio [INR] measurements greater than 1.8) was more reliably achieved in era 2 than in era 1 (50% vs. 34%; P less than .001).

To assess device positioning, the researchers looked at the angle of the inflow cannula, defining malposition as either less than the 5th or greater than the 95th percentile of the median of all the inflow cannula angles. Regarding the outflow cannula, they looked at patients who had bend-relief disconnects, either partial or complete, and those who had radiographic evidence of outflow graft malposition or kink.

Device positioning issues were significantly more prevalent during era 2 than during era 1 (29% vs. 4%). Most of this difference was driven by inflow cannula positioning problems, Dr. Bhama noted.

When the patients with concerns related to device positioning were excluded, the freedom from PT at 24 months no longer differed significantly between groups (P = .094).

The groups were demographically similar except for age, which was higher in the era 2 group (57 years, vs. 50 years for era 1; P = .037). More patients in the era 2 group received an LVAD for destination therapy, although this difference actually wasn’t significant (61% vs. 38%; P = .066).

The groups were also similar with regard to early major adverse events (right ventricular failure, bleeding, infection, and stroke) and medical noncompliance.

In the earlier multicenter study, Dr. Randall C. Starling, of the Cleveland Clinic, and his colleagues reported an abrupt increase in LVAD thrombosis: Between March 2011 and Jan. 1, 2013, the occurrence of PT at 3 months after implantation increased from 2.2% to 8.4% (N. Engl. J. Med. 2014;370:33-40).

"Dissecting the root cause of this problem is an extremely difficult task," said Dr. Nader Moazami, the invited discussant for Dr. Bhama’s presentation and the second author on the Starling paper. Dr. Moazami is surgical director of the Kaufman Center for Heart Failure at the Cleveland Clinic.

"While recent advances in LVAD technology with continuous-flow pumps have saved the lives of thousands of dying patients, issues related to adverse events and the associated morbidity and mortality are of immense importance, specifically as we consider the relevance of this technology to the more ambulatory heart failure patients," said Dr. Moazami, commenting on the study.

However, he suggested that the real cause of the recent increase in PT has not yet been discovered, and questioned the validity of assessing inflow cannula angulation based on a chest x-ray. "This to my knowledge has never been validated and was a concern in about half of the patients in the pump thrombosis group," Dr. Moazami said. Patients with "a demonstrable mechanical reason for pump thrombosis" were excluded from the Starling team’s analysis, he added.

In response, Dr. Bhama cited a study by Dr. Abeel Mangi, a cardiac surgeon at Yale University, New Haven, Conn., which found that greater angulation of the HeartMate II inflow cannula, along with the depth of the pump pocket, correlated with the development of PT (Ann. Thorac. Surg. 2013;96:1259-65).

"These aren’t just angles that are slightly off here and there," noted Dr. Bhama. "These are splayed very widely, situations I think where we all would say this is something we should be concerned about."

Dr. Bhama reported no relevant disclosures.