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Novel metabolite may be key in NAFLD
WASHINGTON – A newly identified metabolite of the gut microbiome may be a potentially useful biomarker in determining the severity of nonalcoholic fatty liver disease (NAFLD) and may provide a new treatment target, according to results of an analysis of serum metabolites isolated from 100 pairs of twins presented at the annual meeting of the American Association for the Study of Liver Diseases.
The researchers at the NAFLD Research Center at the University of California at San Diego isolated a metabolite derived from the gut microbiome, known as 3-(4-hydroxyphenyl)lactate, from 713 serum metabolites they analyzed, 440 of which were identified as heritable, said Cyrielle Caussy, MD, PhD. The researchers further winnowed that pool down to 94 associated with fibrosis alone and 170 associated with hepatic steatosis alone, 56 of which overlapped to have a shared gene effect with both hepatic steatosis and fibrosis, six of which derived from the gut microbiome.
Of the four heritable serum metabolites the researchers found to be significantly associated with NAFLD after adjustment for age, sex and Hispanic ethnicity, 3-(4-hydroxyphenyl)lactate had the highest odds ratio (95% confidence interval): 4.29 (1.87-9.81, P = .0006) vs. phenyllactate (OR 2.12, 1.09-4.10, P = .0258), palmitic acid (2.58, 1.31-5.17, P = .0065) and gamma-glutamylisoleucine (2.98, 1.36-6.51, P = .0062).
Dr. Caussy noted that previous studies have found a strong correlation between bacterial species in the gut and advanced fibrosis in NAFLD (Cell Metab. 2017;25:1054-62). This latest research takes those findings to the next level, Dr. Caussy said. “This metabolite could be a useful biomarker of the severity of NAFLD and may be a target for future treatment of NAFLD and could be used to monitor a treatment response,” she added.
The goal of the study was to determine if any serum metabolites have a shared genetic effect with hepatic steatosis and fibrosis, Dr. Caussy said. “The heritability of serum metabolites associated with NAFLD and their shared gene effect with hepatic steatosis and fibrosis have not been assessed yet,” she noted. The researchers isolated the serum metabolites from a cohort of 100 pairs of twins and 56 other relatives in the Southern California Twins Register, and validated the data in a cohort of 156 patients who had biopsy-proven NAFLD.
Dr. Caussy reported having no financial disclosures.
WASHINGTON – A newly identified metabolite of the gut microbiome may be a potentially useful biomarker in determining the severity of nonalcoholic fatty liver disease (NAFLD) and may provide a new treatment target, according to results of an analysis of serum metabolites isolated from 100 pairs of twins presented at the annual meeting of the American Association for the Study of Liver Diseases.
The researchers at the NAFLD Research Center at the University of California at San Diego isolated a metabolite derived from the gut microbiome, known as 3-(4-hydroxyphenyl)lactate, from 713 serum metabolites they analyzed, 440 of which were identified as heritable, said Cyrielle Caussy, MD, PhD. The researchers further winnowed that pool down to 94 associated with fibrosis alone and 170 associated with hepatic steatosis alone, 56 of which overlapped to have a shared gene effect with both hepatic steatosis and fibrosis, six of which derived from the gut microbiome.
Of the four heritable serum metabolites the researchers found to be significantly associated with NAFLD after adjustment for age, sex and Hispanic ethnicity, 3-(4-hydroxyphenyl)lactate had the highest odds ratio (95% confidence interval): 4.29 (1.87-9.81, P = .0006) vs. phenyllactate (OR 2.12, 1.09-4.10, P = .0258), palmitic acid (2.58, 1.31-5.17, P = .0065) and gamma-glutamylisoleucine (2.98, 1.36-6.51, P = .0062).
Dr. Caussy noted that previous studies have found a strong correlation between bacterial species in the gut and advanced fibrosis in NAFLD (Cell Metab. 2017;25:1054-62). This latest research takes those findings to the next level, Dr. Caussy said. “This metabolite could be a useful biomarker of the severity of NAFLD and may be a target for future treatment of NAFLD and could be used to monitor a treatment response,” she added.
The goal of the study was to determine if any serum metabolites have a shared genetic effect with hepatic steatosis and fibrosis, Dr. Caussy said. “The heritability of serum metabolites associated with NAFLD and their shared gene effect with hepatic steatosis and fibrosis have not been assessed yet,” she noted. The researchers isolated the serum metabolites from a cohort of 100 pairs of twins and 56 other relatives in the Southern California Twins Register, and validated the data in a cohort of 156 patients who had biopsy-proven NAFLD.
Dr. Caussy reported having no financial disclosures.
WASHINGTON – A newly identified metabolite of the gut microbiome may be a potentially useful biomarker in determining the severity of nonalcoholic fatty liver disease (NAFLD) and may provide a new treatment target, according to results of an analysis of serum metabolites isolated from 100 pairs of twins presented at the annual meeting of the American Association for the Study of Liver Diseases.
The researchers at the NAFLD Research Center at the University of California at San Diego isolated a metabolite derived from the gut microbiome, known as 3-(4-hydroxyphenyl)lactate, from 713 serum metabolites they analyzed, 440 of which were identified as heritable, said Cyrielle Caussy, MD, PhD. The researchers further winnowed that pool down to 94 associated with fibrosis alone and 170 associated with hepatic steatosis alone, 56 of which overlapped to have a shared gene effect with both hepatic steatosis and fibrosis, six of which derived from the gut microbiome.
Of the four heritable serum metabolites the researchers found to be significantly associated with NAFLD after adjustment for age, sex and Hispanic ethnicity, 3-(4-hydroxyphenyl)lactate had the highest odds ratio (95% confidence interval): 4.29 (1.87-9.81, P = .0006) vs. phenyllactate (OR 2.12, 1.09-4.10, P = .0258), palmitic acid (2.58, 1.31-5.17, P = .0065) and gamma-glutamylisoleucine (2.98, 1.36-6.51, P = .0062).
Dr. Caussy noted that previous studies have found a strong correlation between bacterial species in the gut and advanced fibrosis in NAFLD (Cell Metab. 2017;25:1054-62). This latest research takes those findings to the next level, Dr. Caussy said. “This metabolite could be a useful biomarker of the severity of NAFLD and may be a target for future treatment of NAFLD and could be used to monitor a treatment response,” she added.
The goal of the study was to determine if any serum metabolites have a shared genetic effect with hepatic steatosis and fibrosis, Dr. Caussy said. “The heritability of serum metabolites associated with NAFLD and their shared gene effect with hepatic steatosis and fibrosis have not been assessed yet,” she noted. The researchers isolated the serum metabolites from a cohort of 100 pairs of twins and 56 other relatives in the Southern California Twins Register, and validated the data in a cohort of 156 patients who had biopsy-proven NAFLD.
Dr. Caussy reported having no financial disclosures.
AT THE LIVER MEETING 2017
Key clinical point: Researchers have identified a novel serum metabolite that may be the key to linking the role of the gut microbiome with the presence of nonalcoholic fatty liver disease (NAFLD)–related fibrosis.
Major finding: An analysis of 713 serum metabolites identified a novel, gut microbiome–derived serum metabolite known as 3-(4-hydroxyphenyl)lactate that had an odds ratio of 4.29 for NAFLD.
Data source: Cross-sectional analysis of a prospective cohort of 156 subjects in the Southern California Twin Study Cohort.
Disclosures: Dr. Caussy reported having no financial disclosures.
Hispanics bear brunt of NAFLD disease burden
WASHINGTON — Significant racial and ethnic disparities exist in nonalcoholic fatty liver disease prevalence and severity in the United States, with Hispanics at highest risk and blacks at the lowest, but the risk of death from NAFLD is highest in whites, according to a meta-analysis of 34 studies presented at the annual meeting of the American Association for the Study of Liver Diseases.
The findings are based on a meta-analysis of studies in the MEDLINE, EMBASE, and Cochrane databases from inception through August 2016 that included 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis, Dr. Rich said.
When the researchers drilled down into the data, they found the disparities dissipated somewhat. “When we looked at the severity of NAFLD we looked at two things: whether there was NASH (nonalcoholic steatohepatitis) present, or if there was the presence of advanced fibrosis,” Dr. Rich said. “We found there was no significant difference in the risk of NASH in Hispanic patients, compared to white patients; however, the proportion of Hispanic NAFLD patients that had NASH was 45.4%, compared to 32.2% in whites.” The pooled relative risk was 1.09.
The meta-analysis tended to attenuate the disparities found in disease severity, compared with the disparities the researchers found in prevalence, Dr. Rich said. “Data are limited and discordant on racial and ethnic differences in NAFLD prognosis and outcomes,” she said. “In the current literature the studies have notable limitations, highlighting the need for future high-quality data in this area, and further studies are needed to determine the need and pathways to reduce NAFLD disparities in the future,” she said.
Dr. Rich had no financial relationships to disclose.
WASHINGTON — Significant racial and ethnic disparities exist in nonalcoholic fatty liver disease prevalence and severity in the United States, with Hispanics at highest risk and blacks at the lowest, but the risk of death from NAFLD is highest in whites, according to a meta-analysis of 34 studies presented at the annual meeting of the American Association for the Study of Liver Diseases.
The findings are based on a meta-analysis of studies in the MEDLINE, EMBASE, and Cochrane databases from inception through August 2016 that included 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis, Dr. Rich said.
When the researchers drilled down into the data, they found the disparities dissipated somewhat. “When we looked at the severity of NAFLD we looked at two things: whether there was NASH (nonalcoholic steatohepatitis) present, or if there was the presence of advanced fibrosis,” Dr. Rich said. “We found there was no significant difference in the risk of NASH in Hispanic patients, compared to white patients; however, the proportion of Hispanic NAFLD patients that had NASH was 45.4%, compared to 32.2% in whites.” The pooled relative risk was 1.09.
The meta-analysis tended to attenuate the disparities found in disease severity, compared with the disparities the researchers found in prevalence, Dr. Rich said. “Data are limited and discordant on racial and ethnic differences in NAFLD prognosis and outcomes,” she said. “In the current literature the studies have notable limitations, highlighting the need for future high-quality data in this area, and further studies are needed to determine the need and pathways to reduce NAFLD disparities in the future,” she said.
Dr. Rich had no financial relationships to disclose.
WASHINGTON — Significant racial and ethnic disparities exist in nonalcoholic fatty liver disease prevalence and severity in the United States, with Hispanics at highest risk and blacks at the lowest, but the risk of death from NAFLD is highest in whites, according to a meta-analysis of 34 studies presented at the annual meeting of the American Association for the Study of Liver Diseases.
The findings are based on a meta-analysis of studies in the MEDLINE, EMBASE, and Cochrane databases from inception through August 2016 that included 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis, Dr. Rich said.
When the researchers drilled down into the data, they found the disparities dissipated somewhat. “When we looked at the severity of NAFLD we looked at two things: whether there was NASH (nonalcoholic steatohepatitis) present, or if there was the presence of advanced fibrosis,” Dr. Rich said. “We found there was no significant difference in the risk of NASH in Hispanic patients, compared to white patients; however, the proportion of Hispanic NAFLD patients that had NASH was 45.4%, compared to 32.2% in whites.” The pooled relative risk was 1.09.
The meta-analysis tended to attenuate the disparities found in disease severity, compared with the disparities the researchers found in prevalence, Dr. Rich said. “Data are limited and discordant on racial and ethnic differences in NAFLD prognosis and outcomes,” she said. “In the current literature the studies have notable limitations, highlighting the need for future high-quality data in this area, and further studies are needed to determine the need and pathways to reduce NAFLD disparities in the future,” she said.
Dr. Rich had no financial relationships to disclose.
AT THE LIVER MEETING 2017
Key clinical point: Hispanics have a much higher incidence of fatty liver disease than other ethnic groups.
Major finding: NAFLD prevalence is highest in Hispanics and lower in blacks, compared with whites, although differences between groups are smaller in high-risk cohorts (range, 47.6%-55.5%) than in population-based cohorts (range, 13.0%-22.9%).
Data source: Meta-analysis of 34 studies in the MEDLINE, EMBASE, and Cochrane databases from inception through August 2016 that involved 368,569 patients.
Disclosures: Dr. Rich had no financial relationships to disclose.
Why VADS is gaining ground in pediatrics
The miniaturization of continuous-flow ventricular assist devices has launched the era of continuous-flow VAD support in pediatric patients, and the trend may accelerate with the introduction of a continuous-flow device designed specifically for small children. In an expert opinion in the Journal of Thoracic and Cardiovascular Surgery, Iki Adachi, MD, of Baylor College of Medicine in Houston, said the emerging science of continuous-flow VADs in children promises to solve problems like device size mismatch, hospital-only VADs, and chronic therapy (J Thorac Cardiovasc Surg. 2017 Oct;154:1358-61). “With ongoing device miniaturization, enthusiasm has been growing among pediatric physicians for the use of continuous-flow VADs in children,” Dr. Adachi said. He noted the introduction of a continuous-flow device for small children, the Infant Jarvik 2015, “may further accelerate the trend.”
Dr. Adachi cited PediMACS reports that stated that more than half of the long-term devices now registered are continuous-flow devices, and that continuous-flow VADs comprised 62% of all durable VAD implants in the third quarter of 2016. “With the encouraging results recorded to date, the use of continuous-flow devices in the pediatric population is rapidly increasing,” he said.
Miniaturization has addressed the problem of size mismatch when using continuous-flow VAD devices in children, he said, noting that use of the Infant Jarvik device may be expanded even further to children as small at 8 kg or less. The PumpKIN trial(Pumps for Kids, Infants, and Neonates), which is evaluating the Infant Jarvik 2015 vs. the Berlin Heart EXCOR, could provide answers on the feasibility of continuous-flow VADs in small children.
“Based on experience with the chronic animal model, I believe that the Infant Jarvik device will properly fit the patients included in the trial,” he said.
Continuous-flow VAD in children also holds potential for managing these patients outside the hospital setting. “Outpatient management of children with continuous-flow VADs has been shown to be feasible,” he said, adding that the PediMACS registry has reported that only 45% of patients have been managed this way. “Nonetheless, with maturation of the pediatric field, outpatient management will become routine rather than the exception,” he said.
Greater use of continuous-flow VADs also may create opportunities to improve the status and suitability for transplantation of children with severe heart failure, he said. He gave as an example his group’s practice at Houston’s Texas Children’s Hospital, which is to deactivate patients on the transplant wait list for 3 months once they start continuous-flow VAD support. “A postoperative ‘grace period’ affords protected opportunities for both physical and psychological recovery,” he said. This timeout of sorts also affords the care team time to assess the myocardium for possible functional recovery.
In patients who are not good candidates for transplantation, durable continuous-flow VADs may provide chronic therapy, and in time, these patients may become suitable transplant candidates, said Dr. Adachi. “Bypassing such an unfavorable period for transplantation with prolonged VAD support may be a reasonable approach,” he said.
Patients with failing single-ventricle circulation also may benefit from VAD support, although the challenges facing this population are more profound than in other groups, Dr. Adachi said. VAD support for single-ventricle disease is sparse, but these patients require careful evaluation of the nature of their condition. “If systolic dysfunction is the predominant cause of circulatory failure, then VAD support for the failing systemic ventricle will likely improve hemodynamics,” said Dr. Adachi. VAD support also could help the patient move through the various stages of palliation.
“Again, the emphasis is not just on simply keeping the patient alive until a donor organ becomes available; rather, attention is refocused on overall health beyond survival, which may eventually affect transplantation candidacy and even post transplantation outcome,” Dr. Adachi concluded.
Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare, and as a consultant for the New England Research Institute related to the PumpKIN trial.
The miniaturization of continuous-flow ventricular assist devices has launched the era of continuous-flow VAD support in pediatric patients, and the trend may accelerate with the introduction of a continuous-flow device designed specifically for small children. In an expert opinion in the Journal of Thoracic and Cardiovascular Surgery, Iki Adachi, MD, of Baylor College of Medicine in Houston, said the emerging science of continuous-flow VADs in children promises to solve problems like device size mismatch, hospital-only VADs, and chronic therapy (J Thorac Cardiovasc Surg. 2017 Oct;154:1358-61). “With ongoing device miniaturization, enthusiasm has been growing among pediatric physicians for the use of continuous-flow VADs in children,” Dr. Adachi said. He noted the introduction of a continuous-flow device for small children, the Infant Jarvik 2015, “may further accelerate the trend.”
Dr. Adachi cited PediMACS reports that stated that more than half of the long-term devices now registered are continuous-flow devices, and that continuous-flow VADs comprised 62% of all durable VAD implants in the third quarter of 2016. “With the encouraging results recorded to date, the use of continuous-flow devices in the pediatric population is rapidly increasing,” he said.
Miniaturization has addressed the problem of size mismatch when using continuous-flow VAD devices in children, he said, noting that use of the Infant Jarvik device may be expanded even further to children as small at 8 kg or less. The PumpKIN trial(Pumps for Kids, Infants, and Neonates), which is evaluating the Infant Jarvik 2015 vs. the Berlin Heart EXCOR, could provide answers on the feasibility of continuous-flow VADs in small children.
“Based on experience with the chronic animal model, I believe that the Infant Jarvik device will properly fit the patients included in the trial,” he said.
Continuous-flow VAD in children also holds potential for managing these patients outside the hospital setting. “Outpatient management of children with continuous-flow VADs has been shown to be feasible,” he said, adding that the PediMACS registry has reported that only 45% of patients have been managed this way. “Nonetheless, with maturation of the pediatric field, outpatient management will become routine rather than the exception,” he said.
Greater use of continuous-flow VADs also may create opportunities to improve the status and suitability for transplantation of children with severe heart failure, he said. He gave as an example his group’s practice at Houston’s Texas Children’s Hospital, which is to deactivate patients on the transplant wait list for 3 months once they start continuous-flow VAD support. “A postoperative ‘grace period’ affords protected opportunities for both physical and psychological recovery,” he said. This timeout of sorts also affords the care team time to assess the myocardium for possible functional recovery.
In patients who are not good candidates for transplantation, durable continuous-flow VADs may provide chronic therapy, and in time, these patients may become suitable transplant candidates, said Dr. Adachi. “Bypassing such an unfavorable period for transplantation with prolonged VAD support may be a reasonable approach,” he said.
Patients with failing single-ventricle circulation also may benefit from VAD support, although the challenges facing this population are more profound than in other groups, Dr. Adachi said. VAD support for single-ventricle disease is sparse, but these patients require careful evaluation of the nature of their condition. “If systolic dysfunction is the predominant cause of circulatory failure, then VAD support for the failing systemic ventricle will likely improve hemodynamics,” said Dr. Adachi. VAD support also could help the patient move through the various stages of palliation.
“Again, the emphasis is not just on simply keeping the patient alive until a donor organ becomes available; rather, attention is refocused on overall health beyond survival, which may eventually affect transplantation candidacy and even post transplantation outcome,” Dr. Adachi concluded.
Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare, and as a consultant for the New England Research Institute related to the PumpKIN trial.
The miniaturization of continuous-flow ventricular assist devices has launched the era of continuous-flow VAD support in pediatric patients, and the trend may accelerate with the introduction of a continuous-flow device designed specifically for small children. In an expert opinion in the Journal of Thoracic and Cardiovascular Surgery, Iki Adachi, MD, of Baylor College of Medicine in Houston, said the emerging science of continuous-flow VADs in children promises to solve problems like device size mismatch, hospital-only VADs, and chronic therapy (J Thorac Cardiovasc Surg. 2017 Oct;154:1358-61). “With ongoing device miniaturization, enthusiasm has been growing among pediatric physicians for the use of continuous-flow VADs in children,” Dr. Adachi said. He noted the introduction of a continuous-flow device for small children, the Infant Jarvik 2015, “may further accelerate the trend.”
Dr. Adachi cited PediMACS reports that stated that more than half of the long-term devices now registered are continuous-flow devices, and that continuous-flow VADs comprised 62% of all durable VAD implants in the third quarter of 2016. “With the encouraging results recorded to date, the use of continuous-flow devices in the pediatric population is rapidly increasing,” he said.
Miniaturization has addressed the problem of size mismatch when using continuous-flow VAD devices in children, he said, noting that use of the Infant Jarvik device may be expanded even further to children as small at 8 kg or less. The PumpKIN trial(Pumps for Kids, Infants, and Neonates), which is evaluating the Infant Jarvik 2015 vs. the Berlin Heart EXCOR, could provide answers on the feasibility of continuous-flow VADs in small children.
“Based on experience with the chronic animal model, I believe that the Infant Jarvik device will properly fit the patients included in the trial,” he said.
Continuous-flow VAD in children also holds potential for managing these patients outside the hospital setting. “Outpatient management of children with continuous-flow VADs has been shown to be feasible,” he said, adding that the PediMACS registry has reported that only 45% of patients have been managed this way. “Nonetheless, with maturation of the pediatric field, outpatient management will become routine rather than the exception,” he said.
Greater use of continuous-flow VADs also may create opportunities to improve the status and suitability for transplantation of children with severe heart failure, he said. He gave as an example his group’s practice at Houston’s Texas Children’s Hospital, which is to deactivate patients on the transplant wait list for 3 months once they start continuous-flow VAD support. “A postoperative ‘grace period’ affords protected opportunities for both physical and psychological recovery,” he said. This timeout of sorts also affords the care team time to assess the myocardium for possible functional recovery.
In patients who are not good candidates for transplantation, durable continuous-flow VADs may provide chronic therapy, and in time, these patients may become suitable transplant candidates, said Dr. Adachi. “Bypassing such an unfavorable period for transplantation with prolonged VAD support may be a reasonable approach,” he said.
Patients with failing single-ventricle circulation also may benefit from VAD support, although the challenges facing this population are more profound than in other groups, Dr. Adachi said. VAD support for single-ventricle disease is sparse, but these patients require careful evaluation of the nature of their condition. “If systolic dysfunction is the predominant cause of circulatory failure, then VAD support for the failing systemic ventricle will likely improve hemodynamics,” said Dr. Adachi. VAD support also could help the patient move through the various stages of palliation.
“Again, the emphasis is not just on simply keeping the patient alive until a donor organ becomes available; rather, attention is refocused on overall health beyond survival, which may eventually affect transplantation candidacy and even post transplantation outcome,” Dr. Adachi concluded.
Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare, and as a consultant for the New England Research Institute related to the PumpKIN trial.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Advances in continuous-flow ventricular assist devices (VADs) promise a paradigm shift in pediatrics.
Major finding: Device miniaturization is solving problems such as size mismatch, inpatients on VADs, and chronic therapy.
Data source: Expert opinion drawing on PediMACS reports and published trials of continuous-flow VAD.
Disclosures: Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare and as a consultant for the New England Research Institute related to the PumpKIN trial.
Challenges of validating cerebral protection for TAVI
While using cerebral embolic protection during transcatheter aortic valve implantation (TAVI) seems appealing to reduce the risk of stroke, which has been reported to be higher than in open aortic valve replacement, the challenge of developing practical CEP devices and then designing appropriate trials may be insurmountable, according to a featured expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154;880-3).
Dr. Messé and Dr. Furie reviewed completed trials of five different CEP devices in 630 patients, noting that the trials confirmed the difficulty of “designing a trial that can prove a clinical benefit.” They noted 30-day stroke rates ranged from 4% to 6.7%, although prospective, nonrandomized European registries reported rates of 3.4% to 4.1%, and a large U.S. registry reported a rate of 2.5%. These results suggest “that some neurologic complications are going undetected or underreported in routine clinical practice.”
That may be a function of the different methods the trials used to determine complications. “There are little data to define best practice, but direct comprehensive assessment by a neurologist is likely the most accurate and sensitive method for detecting clinical stroke,” they added.
Another important factor is the timing of the assessment. They pointed out that half of all 30-day stroke events in TAVI are detected within 2 days of the procedure, but mild or transient symptoms can be missed if the only evaluation occurs just before discharge. “Unfortunately, in most studies this is when the neurologic assessment is performed,” Dr. Messé and Dr. Furie wrote. They added that long-term effects of these strokes have not been well studied.
What’s more, many TAVI patients have subclinical ischemic injury that only neuroimaging can detect. “Studies of MRI performed early after TAVI have demonstrated acute infarcts in 68% to 97% of patients,” the stated. While small and multiple, these microinfarcts may not be totally silent. “Additional studies to assess the long-term implications of clinically silent infarcts are clearly needed,” the coauthors said.
They also noted that a trial of stenting vs. endarterectomy for carotid stenosis raises caution about CEP devices (Lancet Neurol. 2010;9:353-62), as patients who had angioplasty and stenting and were treated with a CEP device had higher rates of acute infarct detected on MRI than those who did not have the CEP. Placing the CEP device through a severely stenosed and symptomatic carotid artery may have led to additional cerebral emboli.
“Placing a cerebral protection device in the aorta for a TAVI procedure also could be problematic in the presence of severe aortic arch disease or variant anatomy,” Dr. Messé and Dr. Furie commented. With two large trials of embolic protection in TAVI currently underway, the coauthors said, “the field eagerly awaits these results.”
Dr. Messé has received research support from GlaxoSmithKline and Direct Flow Medical. Both Dr. Messé and Dr. Furie have participated in the National Institutes of Health/National Heart, Lung, and Blood Institute/National Institute of Neurologic Disorders and Stroke–sponsored Cardiothoracic Surgery Network.
Dr. Messé and Dr. Furie pointed out the difficulty of quantifying the incidence of stroke during TAVI. But the long-term impact of stroke is more important because TAVI, as opposed to surgical aortic valve replacement, is more likely to be performed in a younger, healthier population, John Bozinovski, MD, of the University of British Columbia in Victoria said in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:484-5).
While Dr. Messé and Dr. Furie make a valid point that clinically significant stroke, as opposed to diagnostically apparent stroke, is an important outcome of trials of embolic protection in TAVI, the long-term impact of silent strokes identified only with neuroimaging is unknown, “As such, ‘clinically significant’ stroke carries a nebulous definition,” Dr. Bozinovski said.
Nonetheless, CEP devices may become standard “even without good evidence” to support their use, Dr. Bozinovski said, “or perhaps they will be used infrequently or not at all.” Their uptake by cardiac surgeons will depend on the supporting evidence and their treatment effect. “Not only is it difficult to design an effective device, it is possible that we may not know whether a device is effective or what is the size of that effect,” he said. As Dr. Messé and Dr. Furie point out, “Designing and successfully conducting the trial to do so might never occur.”
Dr. Bozinovski disclosed he was a paid consultant with Edwards Life Sciences.
Dr. Messé and Dr. Furie pointed out the difficulty of quantifying the incidence of stroke during TAVI. But the long-term impact of stroke is more important because TAVI, as opposed to surgical aortic valve replacement, is more likely to be performed in a younger, healthier population, John Bozinovski, MD, of the University of British Columbia in Victoria said in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:484-5).
While Dr. Messé and Dr. Furie make a valid point that clinically significant stroke, as opposed to diagnostically apparent stroke, is an important outcome of trials of embolic protection in TAVI, the long-term impact of silent strokes identified only with neuroimaging is unknown, “As such, ‘clinically significant’ stroke carries a nebulous definition,” Dr. Bozinovski said.
Nonetheless, CEP devices may become standard “even without good evidence” to support their use, Dr. Bozinovski said, “or perhaps they will be used infrequently or not at all.” Their uptake by cardiac surgeons will depend on the supporting evidence and their treatment effect. “Not only is it difficult to design an effective device, it is possible that we may not know whether a device is effective or what is the size of that effect,” he said. As Dr. Messé and Dr. Furie point out, “Designing and successfully conducting the trial to do so might never occur.”
Dr. Bozinovski disclosed he was a paid consultant with Edwards Life Sciences.
Dr. Messé and Dr. Furie pointed out the difficulty of quantifying the incidence of stroke during TAVI. But the long-term impact of stroke is more important because TAVI, as opposed to surgical aortic valve replacement, is more likely to be performed in a younger, healthier population, John Bozinovski, MD, of the University of British Columbia in Victoria said in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:484-5).
While Dr. Messé and Dr. Furie make a valid point that clinically significant stroke, as opposed to diagnostically apparent stroke, is an important outcome of trials of embolic protection in TAVI, the long-term impact of silent strokes identified only with neuroimaging is unknown, “As such, ‘clinically significant’ stroke carries a nebulous definition,” Dr. Bozinovski said.
Nonetheless, CEP devices may become standard “even without good evidence” to support their use, Dr. Bozinovski said, “or perhaps they will be used infrequently or not at all.” Their uptake by cardiac surgeons will depend on the supporting evidence and their treatment effect. “Not only is it difficult to design an effective device, it is possible that we may not know whether a device is effective or what is the size of that effect,” he said. As Dr. Messé and Dr. Furie point out, “Designing and successfully conducting the trial to do so might never occur.”
Dr. Bozinovski disclosed he was a paid consultant with Edwards Life Sciences.
While using cerebral embolic protection during transcatheter aortic valve implantation (TAVI) seems appealing to reduce the risk of stroke, which has been reported to be higher than in open aortic valve replacement, the challenge of developing practical CEP devices and then designing appropriate trials may be insurmountable, according to a featured expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154;880-3).
Dr. Messé and Dr. Furie reviewed completed trials of five different CEP devices in 630 patients, noting that the trials confirmed the difficulty of “designing a trial that can prove a clinical benefit.” They noted 30-day stroke rates ranged from 4% to 6.7%, although prospective, nonrandomized European registries reported rates of 3.4% to 4.1%, and a large U.S. registry reported a rate of 2.5%. These results suggest “that some neurologic complications are going undetected or underreported in routine clinical practice.”
That may be a function of the different methods the trials used to determine complications. “There are little data to define best practice, but direct comprehensive assessment by a neurologist is likely the most accurate and sensitive method for detecting clinical stroke,” they added.
Another important factor is the timing of the assessment. They pointed out that half of all 30-day stroke events in TAVI are detected within 2 days of the procedure, but mild or transient symptoms can be missed if the only evaluation occurs just before discharge. “Unfortunately, in most studies this is when the neurologic assessment is performed,” Dr. Messé and Dr. Furie wrote. They added that long-term effects of these strokes have not been well studied.
What’s more, many TAVI patients have subclinical ischemic injury that only neuroimaging can detect. “Studies of MRI performed early after TAVI have demonstrated acute infarcts in 68% to 97% of patients,” the stated. While small and multiple, these microinfarcts may not be totally silent. “Additional studies to assess the long-term implications of clinically silent infarcts are clearly needed,” the coauthors said.
They also noted that a trial of stenting vs. endarterectomy for carotid stenosis raises caution about CEP devices (Lancet Neurol. 2010;9:353-62), as patients who had angioplasty and stenting and were treated with a CEP device had higher rates of acute infarct detected on MRI than those who did not have the CEP. Placing the CEP device through a severely stenosed and symptomatic carotid artery may have led to additional cerebral emboli.
“Placing a cerebral protection device in the aorta for a TAVI procedure also could be problematic in the presence of severe aortic arch disease or variant anatomy,” Dr. Messé and Dr. Furie commented. With two large trials of embolic protection in TAVI currently underway, the coauthors said, “the field eagerly awaits these results.”
Dr. Messé has received research support from GlaxoSmithKline and Direct Flow Medical. Both Dr. Messé and Dr. Furie have participated in the National Institutes of Health/National Heart, Lung, and Blood Institute/National Institute of Neurologic Disorders and Stroke–sponsored Cardiothoracic Surgery Network.
While using cerebral embolic protection during transcatheter aortic valve implantation (TAVI) seems appealing to reduce the risk of stroke, which has been reported to be higher than in open aortic valve replacement, the challenge of developing practical CEP devices and then designing appropriate trials may be insurmountable, according to a featured expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154;880-3).
Dr. Messé and Dr. Furie reviewed completed trials of five different CEP devices in 630 patients, noting that the trials confirmed the difficulty of “designing a trial that can prove a clinical benefit.” They noted 30-day stroke rates ranged from 4% to 6.7%, although prospective, nonrandomized European registries reported rates of 3.4% to 4.1%, and a large U.S. registry reported a rate of 2.5%. These results suggest “that some neurologic complications are going undetected or underreported in routine clinical practice.”
That may be a function of the different methods the trials used to determine complications. “There are little data to define best practice, but direct comprehensive assessment by a neurologist is likely the most accurate and sensitive method for detecting clinical stroke,” they added.
Another important factor is the timing of the assessment. They pointed out that half of all 30-day stroke events in TAVI are detected within 2 days of the procedure, but mild or transient symptoms can be missed if the only evaluation occurs just before discharge. “Unfortunately, in most studies this is when the neurologic assessment is performed,” Dr. Messé and Dr. Furie wrote. They added that long-term effects of these strokes have not been well studied.
What’s more, many TAVI patients have subclinical ischemic injury that only neuroimaging can detect. “Studies of MRI performed early after TAVI have demonstrated acute infarcts in 68% to 97% of patients,” the stated. While small and multiple, these microinfarcts may not be totally silent. “Additional studies to assess the long-term implications of clinically silent infarcts are clearly needed,” the coauthors said.
They also noted that a trial of stenting vs. endarterectomy for carotid stenosis raises caution about CEP devices (Lancet Neurol. 2010;9:353-62), as patients who had angioplasty and stenting and were treated with a CEP device had higher rates of acute infarct detected on MRI than those who did not have the CEP. Placing the CEP device through a severely stenosed and symptomatic carotid artery may have led to additional cerebral emboli.
“Placing a cerebral protection device in the aorta for a TAVI procedure also could be problematic in the presence of severe aortic arch disease or variant anatomy,” Dr. Messé and Dr. Furie commented. With two large trials of embolic protection in TAVI currently underway, the coauthors said, “the field eagerly awaits these results.”
Dr. Messé has received research support from GlaxoSmithKline and Direct Flow Medical. Both Dr. Messé and Dr. Furie have participated in the National Institutes of Health/National Heart, Lung, and Blood Institute/National Institute of Neurologic Disorders and Stroke–sponsored Cardiothoracic Surgery Network.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Cerebral embolic protection during TAVI is an appealing concept that faces challenges.
Major finding: Developing practical and safe devices and testing them in adequately powered trials are daunting tasks.
Data source: Review of five completed and two ongoing clinical trials of 603 and 613 patients, respectively.
Disclosures: Dr. Messé has received research support from GlaxoSmithKline and Direct Flow Medical. Both Dr. Messé and Dr. Furie have participated in the NIH/NHLBI/NINDS-sponsored Cardiothoracic Surgery Network.
Vascular risks heightened in fibrotic NAFLD
WASHINGTON – The true impact of advanced fibrosis and cirrhosis advancing to serious hepatic and nonhepatic complications in nonalcoholic fatty liver disease remains somewhat a mystery, but a multinational prospective cohort study has found that patients with bridging fibrosis are at risk of nonhepatic malignancies and vascular problems while patients with cirrhosis are prone to predominantly liver-related complications that result in higher rates of death and liver transplant, according to a report presented at the annual meeting of the American Association for the Study of Liver Diseases.
“NAFLD patients with biopsy-proven cirrhosis have a higher mortality and liver-related complications than those with bridging fibrosis, whereas vascular events and nonhepatic malignancies are the commonest complications in those with bridging fibrosis,” said Eduardo Vilar-Gomez, MD, PhD, of Indiana University, Indianapolis. “Among compensated cirrhotic patients, those with Child-Pugh (CP) A6 are at highest risk of liver-related outcomes and mortality.”
Dr. Vilar-Gomez reported on a multicenter, international prospective cohort study of 458 NAFLD patients, 159 with biopsy-proven bridging fibrosis and 299 with compensated cirrhosis (222 with CP A5 and 77 with CP A6) who were followed at six academic centers in four different countries between April 1995 and December 2016.
During a mean follow-up of 5.7 years, 41 patients died, 43 had liver transplants, 90 had initial hepatic decompensation events, 42 were diagnosed with hepatocellular carcinoma (HCC), 14 had major vascular events, and 30 were diagnosed with nonhepatic cancers. The overall death or transplant rates were 3% (four) in the bridging fibrosis group, 14% (32) in the cirrhosis and CP A5 group, and 62% (48) in the cirrhosis and CP A6 group.
Liver-related death rates were also highest among patients with cirrhosis, Dr. Vilar-Gomez said. While the four deaths in the fibrosis patients were evenly split between liver- and non–liver-related causes, 79% of deaths (15) in the cirrhosis and CP A5 patients were liver related, as were all 18 deaths in the cirrhosis and CP A6 group.
“Cirrhotic patients displayed the highest rates of hepatic outcomes overall as compared to those with bridging fibrosis,” Dr. Vilar-Gomez said. Rates of hepatic decompensation were 3% (5) for bridging fibrosis, 18% (40) for cirrhosis and CP A5, and 58% (48) for cirrhosis and CP A6. Likewise, HCC rates were also highest in cirrhotic patients: 9% (21) and 25% (19) for those with CP A5 and CP A6 disease, respectively, vs. 1% (2) for those with bridging fibrosis.
But nonhepatic outcomes were highest among the bridging fibrosis patients, Dr. Vilar-Gomez noted. “These include higher rates of major vascular events – 5% (eight) for those with bridging fibrosis vs. 2% (five) and 1% (one) for those with cirrhosis and CP A5 or CP A6 disease, respectively,” he said. “Rates of nonhepatic malignancies were comparable: 8% (13) for those with bridging fibrosis, 5% (10) for those with cirrhosis and CP5 disease and 9% (7) for those with cirrhosis and CP6 disease.
“Cirrhosis increased the risk of death/transplant, decompensation, and hepatocellular carcinoma by 4.3-, 4.5-, and 3.9-fold, respectively,” Dr. Vilar-Gomez said, “but was associated with a lower risk of vascular events.”
He noted that the study identified a number of risk factors associated with overall mortality and severity of liver disease in cirrhosis compared with bridging fibrosis. Cirrhosis patients tended to be 2-3 years older, had lower body mass index and blood pressure, had higher rates of type 2 diabetes, had lower lipid levels, and had worse liver and renal function.
“Type 2 diabetes and steatosis severity on liver histology, among other factors, were independent predictors for liver-related outcomes,” Dr. Vilar-Gomez said. The findings have implications in assessing patients with advanced NAFLD and for the design and interpretation of clinical trials, he added.
Dr. Vilar-Gomez had no financial relationships to disclose.
WASHINGTON – The true impact of advanced fibrosis and cirrhosis advancing to serious hepatic and nonhepatic complications in nonalcoholic fatty liver disease remains somewhat a mystery, but a multinational prospective cohort study has found that patients with bridging fibrosis are at risk of nonhepatic malignancies and vascular problems while patients with cirrhosis are prone to predominantly liver-related complications that result in higher rates of death and liver transplant, according to a report presented at the annual meeting of the American Association for the Study of Liver Diseases.
“NAFLD patients with biopsy-proven cirrhosis have a higher mortality and liver-related complications than those with bridging fibrosis, whereas vascular events and nonhepatic malignancies are the commonest complications in those with bridging fibrosis,” said Eduardo Vilar-Gomez, MD, PhD, of Indiana University, Indianapolis. “Among compensated cirrhotic patients, those with Child-Pugh (CP) A6 are at highest risk of liver-related outcomes and mortality.”
Dr. Vilar-Gomez reported on a multicenter, international prospective cohort study of 458 NAFLD patients, 159 with biopsy-proven bridging fibrosis and 299 with compensated cirrhosis (222 with CP A5 and 77 with CP A6) who were followed at six academic centers in four different countries between April 1995 and December 2016.
During a mean follow-up of 5.7 years, 41 patients died, 43 had liver transplants, 90 had initial hepatic decompensation events, 42 were diagnosed with hepatocellular carcinoma (HCC), 14 had major vascular events, and 30 were diagnosed with nonhepatic cancers. The overall death or transplant rates were 3% (four) in the bridging fibrosis group, 14% (32) in the cirrhosis and CP A5 group, and 62% (48) in the cirrhosis and CP A6 group.
Liver-related death rates were also highest among patients with cirrhosis, Dr. Vilar-Gomez said. While the four deaths in the fibrosis patients were evenly split between liver- and non–liver-related causes, 79% of deaths (15) in the cirrhosis and CP A5 patients were liver related, as were all 18 deaths in the cirrhosis and CP A6 group.
“Cirrhotic patients displayed the highest rates of hepatic outcomes overall as compared to those with bridging fibrosis,” Dr. Vilar-Gomez said. Rates of hepatic decompensation were 3% (5) for bridging fibrosis, 18% (40) for cirrhosis and CP A5, and 58% (48) for cirrhosis and CP A6. Likewise, HCC rates were also highest in cirrhotic patients: 9% (21) and 25% (19) for those with CP A5 and CP A6 disease, respectively, vs. 1% (2) for those with bridging fibrosis.
But nonhepatic outcomes were highest among the bridging fibrosis patients, Dr. Vilar-Gomez noted. “These include higher rates of major vascular events – 5% (eight) for those with bridging fibrosis vs. 2% (five) and 1% (one) for those with cirrhosis and CP A5 or CP A6 disease, respectively,” he said. “Rates of nonhepatic malignancies were comparable: 8% (13) for those with bridging fibrosis, 5% (10) for those with cirrhosis and CP5 disease and 9% (7) for those with cirrhosis and CP6 disease.
“Cirrhosis increased the risk of death/transplant, decompensation, and hepatocellular carcinoma by 4.3-, 4.5-, and 3.9-fold, respectively,” Dr. Vilar-Gomez said, “but was associated with a lower risk of vascular events.”
He noted that the study identified a number of risk factors associated with overall mortality and severity of liver disease in cirrhosis compared with bridging fibrosis. Cirrhosis patients tended to be 2-3 years older, had lower body mass index and blood pressure, had higher rates of type 2 diabetes, had lower lipid levels, and had worse liver and renal function.
“Type 2 diabetes and steatosis severity on liver histology, among other factors, were independent predictors for liver-related outcomes,” Dr. Vilar-Gomez said. The findings have implications in assessing patients with advanced NAFLD and for the design and interpretation of clinical trials, he added.
Dr. Vilar-Gomez had no financial relationships to disclose.
WASHINGTON – The true impact of advanced fibrosis and cirrhosis advancing to serious hepatic and nonhepatic complications in nonalcoholic fatty liver disease remains somewhat a mystery, but a multinational prospective cohort study has found that patients with bridging fibrosis are at risk of nonhepatic malignancies and vascular problems while patients with cirrhosis are prone to predominantly liver-related complications that result in higher rates of death and liver transplant, according to a report presented at the annual meeting of the American Association for the Study of Liver Diseases.
“NAFLD patients with biopsy-proven cirrhosis have a higher mortality and liver-related complications than those with bridging fibrosis, whereas vascular events and nonhepatic malignancies are the commonest complications in those with bridging fibrosis,” said Eduardo Vilar-Gomez, MD, PhD, of Indiana University, Indianapolis. “Among compensated cirrhotic patients, those with Child-Pugh (CP) A6 are at highest risk of liver-related outcomes and mortality.”
Dr. Vilar-Gomez reported on a multicenter, international prospective cohort study of 458 NAFLD patients, 159 with biopsy-proven bridging fibrosis and 299 with compensated cirrhosis (222 with CP A5 and 77 with CP A6) who were followed at six academic centers in four different countries between April 1995 and December 2016.
During a mean follow-up of 5.7 years, 41 patients died, 43 had liver transplants, 90 had initial hepatic decompensation events, 42 were diagnosed with hepatocellular carcinoma (HCC), 14 had major vascular events, and 30 were diagnosed with nonhepatic cancers. The overall death or transplant rates were 3% (four) in the bridging fibrosis group, 14% (32) in the cirrhosis and CP A5 group, and 62% (48) in the cirrhosis and CP A6 group.
Liver-related death rates were also highest among patients with cirrhosis, Dr. Vilar-Gomez said. While the four deaths in the fibrosis patients were evenly split between liver- and non–liver-related causes, 79% of deaths (15) in the cirrhosis and CP A5 patients were liver related, as were all 18 deaths in the cirrhosis and CP A6 group.
“Cirrhotic patients displayed the highest rates of hepatic outcomes overall as compared to those with bridging fibrosis,” Dr. Vilar-Gomez said. Rates of hepatic decompensation were 3% (5) for bridging fibrosis, 18% (40) for cirrhosis and CP A5, and 58% (48) for cirrhosis and CP A6. Likewise, HCC rates were also highest in cirrhotic patients: 9% (21) and 25% (19) for those with CP A5 and CP A6 disease, respectively, vs. 1% (2) for those with bridging fibrosis.
But nonhepatic outcomes were highest among the bridging fibrosis patients, Dr. Vilar-Gomez noted. “These include higher rates of major vascular events – 5% (eight) for those with bridging fibrosis vs. 2% (five) and 1% (one) for those with cirrhosis and CP A5 or CP A6 disease, respectively,” he said. “Rates of nonhepatic malignancies were comparable: 8% (13) for those with bridging fibrosis, 5% (10) for those with cirrhosis and CP5 disease and 9% (7) for those with cirrhosis and CP6 disease.
“Cirrhosis increased the risk of death/transplant, decompensation, and hepatocellular carcinoma by 4.3-, 4.5-, and 3.9-fold, respectively,” Dr. Vilar-Gomez said, “but was associated with a lower risk of vascular events.”
He noted that the study identified a number of risk factors associated with overall mortality and severity of liver disease in cirrhosis compared with bridging fibrosis. Cirrhosis patients tended to be 2-3 years older, had lower body mass index and blood pressure, had higher rates of type 2 diabetes, had lower lipid levels, and had worse liver and renal function.
“Type 2 diabetes and steatosis severity on liver histology, among other factors, were independent predictors for liver-related outcomes,” Dr. Vilar-Gomez said. The findings have implications in assessing patients with advanced NAFLD and for the design and interpretation of clinical trials, he added.
Dr. Vilar-Gomez had no financial relationships to disclose.
AT THE LIVER MEETING 2017
Key clinical point: Cirrhotic patients with advanced nonalcoholic fatty liver disease are at higher risk for liver-related adverse outcomes whereas patients with bridging fibrosis are more prone to nonhepatic malignancies and vascular events.
Major finding: Overall death or transplant rates were 3% in the bridging fibrosis group, 14% in the cirrhosis and Child-Pugh (CP) A5 group, and 62% in the cirrhosis and CP A6 group
Data source: Multicenter, international prospective cohort study of 458 NAFLD patients with biopsy-proven bridging fibrosis or compensated cirrhosis.
Disclosures: Dr. Vilar-Gomez had no financial relationships to disclose.
New biomarkers improve DILI predictability
WASHINGTON – Researchers have identified six new biomarkers of drug-induced liver injury (DILI) that, when combined with traditional measurements, seemed to better predict the disease course, compared with traditional biomarkers alone, according to a presentation at the annual meeting of the American Association for the Study of Liver Diseases.
In addition, some of these biomarkers may provide a “liquid biopsy” to assess degree of inflammation and mode of hepatocyte death, said Rachel Church, PhD, of the University of North Carolina, Chapel Hill.
“The motivation behind this research is that the standard biomarkers for DILI have several shortcomings,” Dr. Church said. “They’re not entirely liver specific, they’re not mechanistically informative, and they’re not sufficiently predictive of outcome.”
The researchers found that elevated levels of these six candidate biomarkers were predictive for adverse outcome in DILI: total keratin18 (K18); caspase-cleaved K18 (ccK18); alpha-fetoprotein (AFP); osteopontin (OPN); fatty acid–binding protein 1 (FABP1); and macrophage colony-stimulating factor receptor (MCSFR) determined by immunoassay. “We believe that using some of these candidate biomarkers in combination with the standard tests may be the best way to identify individuals at risk for an adverse outcome,” Dr. Church said.
While their analysis found that the traditional international normalized ratio had the overall best predictive value, measured as area under the curve (AUC) of 0.922, the candidate biomarker OPN was second best with an AUC of 0.871, “and actually performed better than total bilirubin,” Dr. Church said.
The study evaluated mechanistic candidate biomarkers by obtaining biopsies in a cohort of 27 patients within 2 weeks of diagnosis, focusing on three physiological reactions: inflammation, necrosis, and apoptosis.
With regard to inflammation, Dr. Church said, “What we found was that MCSFR actually was significantly elevated in patients who had a high score for inflammation; however, there was no significant difference in OPN, although there was a slight elevation.”
They evaluated necrosis using a semiquantitative confluent coagulative necrosis score, and found no difference in the typical biomarkers of cell necrosis, such as alanine transminase, aspartate aminotransferase, and K18. “So we also looked at the regenerative biomarkers, OPN and AFP, and indeed, we observed that both were significantly elevated with high confluent coagulative necrosis scores,” she said.
To evaluate apoptosis, the researchers used the semiquantitative apoptosis score. “We found there was a small but significant elevation in ccK18 in individuals with a high apoptosis score,” she said. They then evaluated the ratio of ccK18 to K18. “The closer the score is to 1, the more apoptosis you have; and the closer the score is to 0, the more necrosis you have,” Dr. Church said.
They also developed a predictive model that combined the traditional biomarkers INR, total bilirubin, and aspartate aminotransferase with the candidate biomarkers OPN and K18, which had an AUC of 0.97. “Some analysis of candidate biomarkers in combination with tests such as MELD score [Model for End-Stage Liver Disease] and ‘Hy’s Law’ saw that incorporating candidate biomarkers was useful,” Dr. Church said.
Dr. Church reported having no financial disclosures.
WASHINGTON – Researchers have identified six new biomarkers of drug-induced liver injury (DILI) that, when combined with traditional measurements, seemed to better predict the disease course, compared with traditional biomarkers alone, according to a presentation at the annual meeting of the American Association for the Study of Liver Diseases.
In addition, some of these biomarkers may provide a “liquid biopsy” to assess degree of inflammation and mode of hepatocyte death, said Rachel Church, PhD, of the University of North Carolina, Chapel Hill.
“The motivation behind this research is that the standard biomarkers for DILI have several shortcomings,” Dr. Church said. “They’re not entirely liver specific, they’re not mechanistically informative, and they’re not sufficiently predictive of outcome.”
The researchers found that elevated levels of these six candidate biomarkers were predictive for adverse outcome in DILI: total keratin18 (K18); caspase-cleaved K18 (ccK18); alpha-fetoprotein (AFP); osteopontin (OPN); fatty acid–binding protein 1 (FABP1); and macrophage colony-stimulating factor receptor (MCSFR) determined by immunoassay. “We believe that using some of these candidate biomarkers in combination with the standard tests may be the best way to identify individuals at risk for an adverse outcome,” Dr. Church said.
While their analysis found that the traditional international normalized ratio had the overall best predictive value, measured as area under the curve (AUC) of 0.922, the candidate biomarker OPN was second best with an AUC of 0.871, “and actually performed better than total bilirubin,” Dr. Church said.
The study evaluated mechanistic candidate biomarkers by obtaining biopsies in a cohort of 27 patients within 2 weeks of diagnosis, focusing on three physiological reactions: inflammation, necrosis, and apoptosis.
With regard to inflammation, Dr. Church said, “What we found was that MCSFR actually was significantly elevated in patients who had a high score for inflammation; however, there was no significant difference in OPN, although there was a slight elevation.”
They evaluated necrosis using a semiquantitative confluent coagulative necrosis score, and found no difference in the typical biomarkers of cell necrosis, such as alanine transminase, aspartate aminotransferase, and K18. “So we also looked at the regenerative biomarkers, OPN and AFP, and indeed, we observed that both were significantly elevated with high confluent coagulative necrosis scores,” she said.
To evaluate apoptosis, the researchers used the semiquantitative apoptosis score. “We found there was a small but significant elevation in ccK18 in individuals with a high apoptosis score,” she said. They then evaluated the ratio of ccK18 to K18. “The closer the score is to 1, the more apoptosis you have; and the closer the score is to 0, the more necrosis you have,” Dr. Church said.
They also developed a predictive model that combined the traditional biomarkers INR, total bilirubin, and aspartate aminotransferase with the candidate biomarkers OPN and K18, which had an AUC of 0.97. “Some analysis of candidate biomarkers in combination with tests such as MELD score [Model for End-Stage Liver Disease] and ‘Hy’s Law’ saw that incorporating candidate biomarkers was useful,” Dr. Church said.
Dr. Church reported having no financial disclosures.
WASHINGTON – Researchers have identified six new biomarkers of drug-induced liver injury (DILI) that, when combined with traditional measurements, seemed to better predict the disease course, compared with traditional biomarkers alone, according to a presentation at the annual meeting of the American Association for the Study of Liver Diseases.
In addition, some of these biomarkers may provide a “liquid biopsy” to assess degree of inflammation and mode of hepatocyte death, said Rachel Church, PhD, of the University of North Carolina, Chapel Hill.
“The motivation behind this research is that the standard biomarkers for DILI have several shortcomings,” Dr. Church said. “They’re not entirely liver specific, they’re not mechanistically informative, and they’re not sufficiently predictive of outcome.”
The researchers found that elevated levels of these six candidate biomarkers were predictive for adverse outcome in DILI: total keratin18 (K18); caspase-cleaved K18 (ccK18); alpha-fetoprotein (AFP); osteopontin (OPN); fatty acid–binding protein 1 (FABP1); and macrophage colony-stimulating factor receptor (MCSFR) determined by immunoassay. “We believe that using some of these candidate biomarkers in combination with the standard tests may be the best way to identify individuals at risk for an adverse outcome,” Dr. Church said.
While their analysis found that the traditional international normalized ratio had the overall best predictive value, measured as area under the curve (AUC) of 0.922, the candidate biomarker OPN was second best with an AUC of 0.871, “and actually performed better than total bilirubin,” Dr. Church said.
The study evaluated mechanistic candidate biomarkers by obtaining biopsies in a cohort of 27 patients within 2 weeks of diagnosis, focusing on three physiological reactions: inflammation, necrosis, and apoptosis.
With regard to inflammation, Dr. Church said, “What we found was that MCSFR actually was significantly elevated in patients who had a high score for inflammation; however, there was no significant difference in OPN, although there was a slight elevation.”
They evaluated necrosis using a semiquantitative confluent coagulative necrosis score, and found no difference in the typical biomarkers of cell necrosis, such as alanine transminase, aspartate aminotransferase, and K18. “So we also looked at the regenerative biomarkers, OPN and AFP, and indeed, we observed that both were significantly elevated with high confluent coagulative necrosis scores,” she said.
To evaluate apoptosis, the researchers used the semiquantitative apoptosis score. “We found there was a small but significant elevation in ccK18 in individuals with a high apoptosis score,” she said. They then evaluated the ratio of ccK18 to K18. “The closer the score is to 1, the more apoptosis you have; and the closer the score is to 0, the more necrosis you have,” Dr. Church said.
They also developed a predictive model that combined the traditional biomarkers INR, total bilirubin, and aspartate aminotransferase with the candidate biomarkers OPN and K18, which had an AUC of 0.97. “Some analysis of candidate biomarkers in combination with tests such as MELD score [Model for End-Stage Liver Disease] and ‘Hy’s Law’ saw that incorporating candidate biomarkers was useful,” Dr. Church said.
Dr. Church reported having no financial disclosures.
AT THE LIVER MEETING 2017
Key clinical point: Combining six candidate biomarkers with traditional biomarkers may improve prediction of adverse outcomes in drug-induced liver injury.
Major finding: Candidate biomarker osteopontin had an area under the cure measure of 0.871, second only to the traditional biomarker international normalized ratio and exceeding that of total bilirubin.
Data source: Analysis of serum samples collected by the DILI Network from 145 patients with a greater than 50% likelihood of having DILI.
Disclosures: Dr. Church reported having no financial disclosures.
Can arterial switch operation impact cognitive deficits?
With dramatic advances of neonatal repair of complex cardiac disease, the population of adults with congenital heart disease (CHD) has increased dramatically, and while studies have shown an increased risk of neurodevelopmental and psychological disorders in these patients, few studies have evaluated their cognitive and psychosocial outcomes. Now, a review of young adults who had an arterial switch operation for transposition of the great arteries in France has found that they have almost twice the rate of cognitive difficulties and more than triple the rate of cognitive impairment as healthy peers.
“Despite satisfactory outcomes in most adults with transposition of the great arteries (TGA), a substantial proportion has cognitive or psychologic difficulties that may reduce their academic success and quality of life,” said lead author David Kalfa, MD, PhD, of Morgan Stanley Children’s Hospital of New York-Presbyterian, Columbia University Medical Center and coauthors in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:1028-35).
The study involved a review of 67 adults aged 18 and older born with TGA between 1984 and 1985 who had an arterial switch operation (ASO) at two hospitals in France: Necker Children’s Hospital in Paris and Marie Lannelongue Hospital in Le Plessis-Robinson. The researchers performed a matched analysis with 43 healthy subjects for age, gender, and education level.
The researchers found that 69% of the TGA patients had an intelligence quotient in the normal range of 85-115. The TGA patients had lower quotients for mean full-scale (94.9 plus or minus 15.3 vs. 103.4 plus or minus 12.3 in healthy subjects; P = 0.003), verbal (96.8 plus or minus 16.2 vs. 102.5 plus or minus 11.5; P =.033) and performance intelligence (93.7 plus or minus 14.6 vs. 103.8 plus or minus 14.3; P less than .001).
The TGA patients also had higher rates of cognitive difficulties, measured as intelligence quotient less than or equal to –1 standard deviation, and cognitive impairment, measured as intelligence quotient less than or equal to –2 standard deviation; 31% vs. 16% (P = .001) for the former and 6% vs. 2% (P = .030) for the latter.
TGA patients with cognitive difficulties had lower educational levels and were also more likely to repeat grades in school, Dr. Kalfa and coauthors noted. “Patients reported an overall satisfactory health-related quality of life,” Dr. Kalfa and coauthors said of the TGA group; “however, those with cognitive or psychologic difficulties reported poorer quality of life.” The researchers identified three predictors of worse outcomes: lower parental socioeconomic and educational status; older age at surgery; and longer hospital stays.
“Our findings suggest that the cognitive morbidities commonly reported in children and adolescents with complex CHD persist into adulthood in individuals with TGA after the ASO,” Dr. Kalfa and coauthors said. Future research should evaluate specific cognitive domains such as attention, memory, and executive functions. “This consideration is important for evaluation of the whole [adult] CHD population because specific cognitive impairments are increasingly documented into adolescence but remain rarely investigated in adulthood,” the researchers said.
Dr. Kalfa and coauthors reported having no financial disclosures.
The findings by Dr. Kalfa and coauthors may point the way to improve cognitive outcomes in children who have the arterial switch operation, said Ryan R. Davies, MD, of A.I duPont Hospital for Children in Wilmington, Del., in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:1036-7.) “Modifiable factors may exist both during the perioperative stage (perfusion strategies, intensive care management) and over the longer term (early neurocognitive assessments and interventions,” Dr. Davies said.
That parental socioeconomic status is associated with cognitive performance suggests early intervention and education “may pay long-term dividends,” Dr. Davies said. Future studies should focus on the impact of specific interventions and identify modifiable developmental factors, he said.
Dr. Kalfa and coauthors have provided an “important start” in that direction, Dr. Davies said. “They have shown that the neurodevelopmental deficits seen early in children with CHD persist into adulthood,” he said. “There are also hints here as to where interventions may be effective in ameliorating those deficits.”
Dr. Davies reported having no financial disclosures.
The findings by Dr. Kalfa and coauthors may point the way to improve cognitive outcomes in children who have the arterial switch operation, said Ryan R. Davies, MD, of A.I duPont Hospital for Children in Wilmington, Del., in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:1036-7.) “Modifiable factors may exist both during the perioperative stage (perfusion strategies, intensive care management) and over the longer term (early neurocognitive assessments and interventions,” Dr. Davies said.
That parental socioeconomic status is associated with cognitive performance suggests early intervention and education “may pay long-term dividends,” Dr. Davies said. Future studies should focus on the impact of specific interventions and identify modifiable developmental factors, he said.
Dr. Kalfa and coauthors have provided an “important start” in that direction, Dr. Davies said. “They have shown that the neurodevelopmental deficits seen early in children with CHD persist into adulthood,” he said. “There are also hints here as to where interventions may be effective in ameliorating those deficits.”
Dr. Davies reported having no financial disclosures.
The findings by Dr. Kalfa and coauthors may point the way to improve cognitive outcomes in children who have the arterial switch operation, said Ryan R. Davies, MD, of A.I duPont Hospital for Children in Wilmington, Del., in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:1036-7.) “Modifiable factors may exist both during the perioperative stage (perfusion strategies, intensive care management) and over the longer term (early neurocognitive assessments and interventions,” Dr. Davies said.
That parental socioeconomic status is associated with cognitive performance suggests early intervention and education “may pay long-term dividends,” Dr. Davies said. Future studies should focus on the impact of specific interventions and identify modifiable developmental factors, he said.
Dr. Kalfa and coauthors have provided an “important start” in that direction, Dr. Davies said. “They have shown that the neurodevelopmental deficits seen early in children with CHD persist into adulthood,” he said. “There are also hints here as to where interventions may be effective in ameliorating those deficits.”
Dr. Davies reported having no financial disclosures.
With dramatic advances of neonatal repair of complex cardiac disease, the population of adults with congenital heart disease (CHD) has increased dramatically, and while studies have shown an increased risk of neurodevelopmental and psychological disorders in these patients, few studies have evaluated their cognitive and psychosocial outcomes. Now, a review of young adults who had an arterial switch operation for transposition of the great arteries in France has found that they have almost twice the rate of cognitive difficulties and more than triple the rate of cognitive impairment as healthy peers.
“Despite satisfactory outcomes in most adults with transposition of the great arteries (TGA), a substantial proportion has cognitive or psychologic difficulties that may reduce their academic success and quality of life,” said lead author David Kalfa, MD, PhD, of Morgan Stanley Children’s Hospital of New York-Presbyterian, Columbia University Medical Center and coauthors in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:1028-35).
The study involved a review of 67 adults aged 18 and older born with TGA between 1984 and 1985 who had an arterial switch operation (ASO) at two hospitals in France: Necker Children’s Hospital in Paris and Marie Lannelongue Hospital in Le Plessis-Robinson. The researchers performed a matched analysis with 43 healthy subjects for age, gender, and education level.
The researchers found that 69% of the TGA patients had an intelligence quotient in the normal range of 85-115. The TGA patients had lower quotients for mean full-scale (94.9 plus or minus 15.3 vs. 103.4 plus or minus 12.3 in healthy subjects; P = 0.003), verbal (96.8 plus or minus 16.2 vs. 102.5 plus or minus 11.5; P =.033) and performance intelligence (93.7 plus or minus 14.6 vs. 103.8 plus or minus 14.3; P less than .001).
The TGA patients also had higher rates of cognitive difficulties, measured as intelligence quotient less than or equal to –1 standard deviation, and cognitive impairment, measured as intelligence quotient less than or equal to –2 standard deviation; 31% vs. 16% (P = .001) for the former and 6% vs. 2% (P = .030) for the latter.
TGA patients with cognitive difficulties had lower educational levels and were also more likely to repeat grades in school, Dr. Kalfa and coauthors noted. “Patients reported an overall satisfactory health-related quality of life,” Dr. Kalfa and coauthors said of the TGA group; “however, those with cognitive or psychologic difficulties reported poorer quality of life.” The researchers identified three predictors of worse outcomes: lower parental socioeconomic and educational status; older age at surgery; and longer hospital stays.
“Our findings suggest that the cognitive morbidities commonly reported in children and adolescents with complex CHD persist into adulthood in individuals with TGA after the ASO,” Dr. Kalfa and coauthors said. Future research should evaluate specific cognitive domains such as attention, memory, and executive functions. “This consideration is important for evaluation of the whole [adult] CHD population because specific cognitive impairments are increasingly documented into adolescence but remain rarely investigated in adulthood,” the researchers said.
Dr. Kalfa and coauthors reported having no financial disclosures.
With dramatic advances of neonatal repair of complex cardiac disease, the population of adults with congenital heart disease (CHD) has increased dramatically, and while studies have shown an increased risk of neurodevelopmental and psychological disorders in these patients, few studies have evaluated their cognitive and psychosocial outcomes. Now, a review of young adults who had an arterial switch operation for transposition of the great arteries in France has found that they have almost twice the rate of cognitive difficulties and more than triple the rate of cognitive impairment as healthy peers.
“Despite satisfactory outcomes in most adults with transposition of the great arteries (TGA), a substantial proportion has cognitive or psychologic difficulties that may reduce their academic success and quality of life,” said lead author David Kalfa, MD, PhD, of Morgan Stanley Children’s Hospital of New York-Presbyterian, Columbia University Medical Center and coauthors in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:1028-35).
The study involved a review of 67 adults aged 18 and older born with TGA between 1984 and 1985 who had an arterial switch operation (ASO) at two hospitals in France: Necker Children’s Hospital in Paris and Marie Lannelongue Hospital in Le Plessis-Robinson. The researchers performed a matched analysis with 43 healthy subjects for age, gender, and education level.
The researchers found that 69% of the TGA patients had an intelligence quotient in the normal range of 85-115. The TGA patients had lower quotients for mean full-scale (94.9 plus or minus 15.3 vs. 103.4 plus or minus 12.3 in healthy subjects; P = 0.003), verbal (96.8 plus or minus 16.2 vs. 102.5 plus or minus 11.5; P =.033) and performance intelligence (93.7 plus or minus 14.6 vs. 103.8 plus or minus 14.3; P less than .001).
The TGA patients also had higher rates of cognitive difficulties, measured as intelligence quotient less than or equal to –1 standard deviation, and cognitive impairment, measured as intelligence quotient less than or equal to –2 standard deviation; 31% vs. 16% (P = .001) for the former and 6% vs. 2% (P = .030) for the latter.
TGA patients with cognitive difficulties had lower educational levels and were also more likely to repeat grades in school, Dr. Kalfa and coauthors noted. “Patients reported an overall satisfactory health-related quality of life,” Dr. Kalfa and coauthors said of the TGA group; “however, those with cognitive or psychologic difficulties reported poorer quality of life.” The researchers identified three predictors of worse outcomes: lower parental socioeconomic and educational status; older age at surgery; and longer hospital stays.
“Our findings suggest that the cognitive morbidities commonly reported in children and adolescents with complex CHD persist into adulthood in individuals with TGA after the ASO,” Dr. Kalfa and coauthors said. Future research should evaluate specific cognitive domains such as attention, memory, and executive functions. “This consideration is important for evaluation of the whole [adult] CHD population because specific cognitive impairments are increasingly documented into adolescence but remain rarely investigated in adulthood,” the researchers said.
Dr. Kalfa and coauthors reported having no financial disclosures.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: A substantial proportion of young adults who had transposition of the great arteries have cognitive or psychological difficulties.
Major finding: Cognitive difficulties were significantly more frequent in the study population than the general population, 31% vs. 16%.
Data source: Age-, gender-, and education level–matched population of 67 young adults with transposition of the great arteries and 43 healthy subjects.
Disclosures: Dr. Kalfa and coauthors reported having no financial disclosures.
Study finds bivalirudin efficacy for PCI no better than heparin
A large study of more than 6,000 heart patients in Sweden has found that patients having percutaneous coronary intervention who received bivalirudin did not have lower rates of deleterious outcomes – death, heart attack, or major bleeding – than did patients who received heparin monotherapy, a contrast to previous trials that found that bivalirudin had a lower bleeding risk than heparin alone after PCI.
The findings were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
The study sought to explain the conflicting findings of previous trials investigating the efficacy of bivalirudin vs. heparin monotherapy. The VALIDATE-SWEDEHEART trial evaluated 6,006 patients who had PCI from June 2014 to September 2016, 90.3% via radial-artery access. This trial differed from previous studies because it was conducted after radial-artery access was routine and potent P2Y12 inhibitors were available, and earlier trials did not compare bivalirudin to heparin monotherapy, said David Erlinge, MD, PhD, of Lund (Sweden) University, and 38 coauthors (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1706443).
The Swedish investigators evaluated the primary endpoint – the composite of any-cause death, MI or major bleeding – during 180 days of follow-up. Among the study patients, 3,005 had ST-segment elevation MI (STEMI) and 3,001 non-STEMI (NSTEMI). All had undergone urgent PCI and most were also on P2Y inhibitors. The P2Y12 inhibitors used were ticagrelor in 5,697 patients (94.9%), prasugrel in 125 (2.1%) and cangrelor in 21 (0.3%).
Study patients with STEMI were permitted to receive up to 5,000 U of intravenous unfractionated heparin before arrival in the catheterization laboratory, and both STEMI and non-STEMI patients who had not received heparin previously could receive up to 3,000 U of intra-arterial heparin before angiography. All patients received aspirin pretreatment, and 62% received potent P2Y12 inhibitors at least one hour before PCI.
After angiography, but before PCI, patients were randomized 1:1 to receive in an open-label fashion either intravenous bivalirudin (The Medicines Company), or intra-arterial unfractionated heparin (LEO Pharma). Bivalirudin was administered as a bolus of 0.75 mg/kg of body weight followed by an infusion of 1.7 mg/kg per hour.
Research nurses contacted patients by phone 7 and 180 days after PCI. Baseline characteristics were similar between the bivalirudin and heparin groups. For example, around 31% of both groups had hyperlipidemia, and 15.2% of the bivalirudin group and 14.2% of the heparin group had a previous PCI.
“The rate of the primary endpoint did not differ significantly between the treatment groups at 30 days after PCI,” Dr. Erlinge and his coauthors noted. At 30 days, 7.2% of the bivalirudin patients and 8% of the heparin group had one of the primary endpoint outcomes, a nonsignificant difference. At 180 days, 12.3% of the bivalirudin group and 12.8% of those receiving heparin had one of the primary endpoint outcomes, also a nonsignificant difference.
Specific outcomes in the bivalirudin vs. heparin patients, respectively, at 180 days were: MI, 2% vs. 2.4%; major bleeding, 8.6% in both groups; stent thrombosis, 0.4% vs. 0.7%; and death from any cause, 2.9% vs. 2.8%, all nonsignificant differences.
“Results were consistent between patients with STEMI and those with NSTEMI and across all other prespecified subgroups,” the researchers wrote. They noted that women in the bivalirudin group had a lower, although not statistically significant, primary endpoint rate than did women in the heparin group.
In this trial, the high rate of radial-artery access and the low use of glycoprotein IIb/IIIa inhibitors may explain the low bleeding rates, the researchers said.
Among the study limitations were that patients excluded from the trial were at higher risk for a primary endpoint than those enrolled, the open-label design may have biased participating physicians in identifying outcomes, the telephone call-based follow-up may have been inherently unreliable, and the fact that most patients received a small dose of heparin before randomization may have reconciled any differences between the two drugs.
Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from Astra Zeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
After considering the findings of the VALIDATE-SWEDEHEART trial, Gregg W. Stone, MD, said in an accompanying editorial, “there is no definitive answer to the question of whether to use bivalirudin or heparin during PCI.”
Dr. Stone, of New York–Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, noted four potential flaws in the study findings. One, the 30-day interval may be a better for evaluating procedural anticoagulation than 180 days – and at 30 days the Swedish study showed “a nonsignificant trend in favor of bivalirudin.” Two, the composite primary endpoint could bias outcomes because individual measures could essentially cancel each other out. Three, differences between treatment groups could have been further minimized because 91% of patients who received bivalirudin also received a substantial dose of heparin before and during PCI. Finally, Dr. Stone said, the study was underpowered to examine the individual components of outcomes.
The data comparing outcomes in STEMI and NSTEMI patients did not show separate results for death, bleeding, and stent thrombosis. Dr. Stone pointed to a meta-analysis of six randomized trials of 14,095 patients with STEMI, showing that bivalirudin had lower rates of major bleeding and 30-day death but higher rates of stent thrombosis than heparin, and that mortality was lower regardless of the use of femoral artery or radial-artery access or other procedural factors. By contrast, previous trials did show similar rates of death, MI, and stent thrombosis between both treatment groups, although lower bleeding rates were seen with bivalirudin.
More definitive answers may lie in investigators from the large-scale randomized trials comparing the anticoagulant agents, including the Swedish authors, combining their data on more than 36,000 patients into a single database, as they have agreed to do, Dr. Stone said. That “should provide robust evidence to guide decisions regarding anticoagulation among patients with STEMI and NSTEMI,” he concluded.
Dr. Stone had no relevant financial relationships to disclose. He made his comments in an invited editorial in the New England Journal of Medicine (doi: 10.1056/NEJMe1709247).
After considering the findings of the VALIDATE-SWEDEHEART trial, Gregg W. Stone, MD, said in an accompanying editorial, “there is no definitive answer to the question of whether to use bivalirudin or heparin during PCI.”
Dr. Stone, of New York–Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, noted four potential flaws in the study findings. One, the 30-day interval may be a better for evaluating procedural anticoagulation than 180 days – and at 30 days the Swedish study showed “a nonsignificant trend in favor of bivalirudin.” Two, the composite primary endpoint could bias outcomes because individual measures could essentially cancel each other out. Three, differences between treatment groups could have been further minimized because 91% of patients who received bivalirudin also received a substantial dose of heparin before and during PCI. Finally, Dr. Stone said, the study was underpowered to examine the individual components of outcomes.
The data comparing outcomes in STEMI and NSTEMI patients did not show separate results for death, bleeding, and stent thrombosis. Dr. Stone pointed to a meta-analysis of six randomized trials of 14,095 patients with STEMI, showing that bivalirudin had lower rates of major bleeding and 30-day death but higher rates of stent thrombosis than heparin, and that mortality was lower regardless of the use of femoral artery or radial-artery access or other procedural factors. By contrast, previous trials did show similar rates of death, MI, and stent thrombosis between both treatment groups, although lower bleeding rates were seen with bivalirudin.
More definitive answers may lie in investigators from the large-scale randomized trials comparing the anticoagulant agents, including the Swedish authors, combining their data on more than 36,000 patients into a single database, as they have agreed to do, Dr. Stone said. That “should provide robust evidence to guide decisions regarding anticoagulation among patients with STEMI and NSTEMI,” he concluded.
Dr. Stone had no relevant financial relationships to disclose. He made his comments in an invited editorial in the New England Journal of Medicine (doi: 10.1056/NEJMe1709247).
After considering the findings of the VALIDATE-SWEDEHEART trial, Gregg W. Stone, MD, said in an accompanying editorial, “there is no definitive answer to the question of whether to use bivalirudin or heparin during PCI.”
Dr. Stone, of New York–Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, noted four potential flaws in the study findings. One, the 30-day interval may be a better for evaluating procedural anticoagulation than 180 days – and at 30 days the Swedish study showed “a nonsignificant trend in favor of bivalirudin.” Two, the composite primary endpoint could bias outcomes because individual measures could essentially cancel each other out. Three, differences between treatment groups could have been further minimized because 91% of patients who received bivalirudin also received a substantial dose of heparin before and during PCI. Finally, Dr. Stone said, the study was underpowered to examine the individual components of outcomes.
The data comparing outcomes in STEMI and NSTEMI patients did not show separate results for death, bleeding, and stent thrombosis. Dr. Stone pointed to a meta-analysis of six randomized trials of 14,095 patients with STEMI, showing that bivalirudin had lower rates of major bleeding and 30-day death but higher rates of stent thrombosis than heparin, and that mortality was lower regardless of the use of femoral artery or radial-artery access or other procedural factors. By contrast, previous trials did show similar rates of death, MI, and stent thrombosis between both treatment groups, although lower bleeding rates were seen with bivalirudin.
More definitive answers may lie in investigators from the large-scale randomized trials comparing the anticoagulant agents, including the Swedish authors, combining their data on more than 36,000 patients into a single database, as they have agreed to do, Dr. Stone said. That “should provide robust evidence to guide decisions regarding anticoagulation among patients with STEMI and NSTEMI,” he concluded.
Dr. Stone had no relevant financial relationships to disclose. He made his comments in an invited editorial in the New England Journal of Medicine (doi: 10.1056/NEJMe1709247).
A large study of more than 6,000 heart patients in Sweden has found that patients having percutaneous coronary intervention who received bivalirudin did not have lower rates of deleterious outcomes – death, heart attack, or major bleeding – than did patients who received heparin monotherapy, a contrast to previous trials that found that bivalirudin had a lower bleeding risk than heparin alone after PCI.
The findings were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
The study sought to explain the conflicting findings of previous trials investigating the efficacy of bivalirudin vs. heparin monotherapy. The VALIDATE-SWEDEHEART trial evaluated 6,006 patients who had PCI from June 2014 to September 2016, 90.3% via radial-artery access. This trial differed from previous studies because it was conducted after radial-artery access was routine and potent P2Y12 inhibitors were available, and earlier trials did not compare bivalirudin to heparin monotherapy, said David Erlinge, MD, PhD, of Lund (Sweden) University, and 38 coauthors (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1706443).
The Swedish investigators evaluated the primary endpoint – the composite of any-cause death, MI or major bleeding – during 180 days of follow-up. Among the study patients, 3,005 had ST-segment elevation MI (STEMI) and 3,001 non-STEMI (NSTEMI). All had undergone urgent PCI and most were also on P2Y inhibitors. The P2Y12 inhibitors used were ticagrelor in 5,697 patients (94.9%), prasugrel in 125 (2.1%) and cangrelor in 21 (0.3%).
Study patients with STEMI were permitted to receive up to 5,000 U of intravenous unfractionated heparin before arrival in the catheterization laboratory, and both STEMI and non-STEMI patients who had not received heparin previously could receive up to 3,000 U of intra-arterial heparin before angiography. All patients received aspirin pretreatment, and 62% received potent P2Y12 inhibitors at least one hour before PCI.
After angiography, but before PCI, patients were randomized 1:1 to receive in an open-label fashion either intravenous bivalirudin (The Medicines Company), or intra-arterial unfractionated heparin (LEO Pharma). Bivalirudin was administered as a bolus of 0.75 mg/kg of body weight followed by an infusion of 1.7 mg/kg per hour.
Research nurses contacted patients by phone 7 and 180 days after PCI. Baseline characteristics were similar between the bivalirudin and heparin groups. For example, around 31% of both groups had hyperlipidemia, and 15.2% of the bivalirudin group and 14.2% of the heparin group had a previous PCI.
“The rate of the primary endpoint did not differ significantly between the treatment groups at 30 days after PCI,” Dr. Erlinge and his coauthors noted. At 30 days, 7.2% of the bivalirudin patients and 8% of the heparin group had one of the primary endpoint outcomes, a nonsignificant difference. At 180 days, 12.3% of the bivalirudin group and 12.8% of those receiving heparin had one of the primary endpoint outcomes, also a nonsignificant difference.
Specific outcomes in the bivalirudin vs. heparin patients, respectively, at 180 days were: MI, 2% vs. 2.4%; major bleeding, 8.6% in both groups; stent thrombosis, 0.4% vs. 0.7%; and death from any cause, 2.9% vs. 2.8%, all nonsignificant differences.
“Results were consistent between patients with STEMI and those with NSTEMI and across all other prespecified subgroups,” the researchers wrote. They noted that women in the bivalirudin group had a lower, although not statistically significant, primary endpoint rate than did women in the heparin group.
In this trial, the high rate of radial-artery access and the low use of glycoprotein IIb/IIIa inhibitors may explain the low bleeding rates, the researchers said.
Among the study limitations were that patients excluded from the trial were at higher risk for a primary endpoint than those enrolled, the open-label design may have biased participating physicians in identifying outcomes, the telephone call-based follow-up may have been inherently unreliable, and the fact that most patients received a small dose of heparin before randomization may have reconciled any differences between the two drugs.
Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from Astra Zeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
A large study of more than 6,000 heart patients in Sweden has found that patients having percutaneous coronary intervention who received bivalirudin did not have lower rates of deleterious outcomes – death, heart attack, or major bleeding – than did patients who received heparin monotherapy, a contrast to previous trials that found that bivalirudin had a lower bleeding risk than heparin alone after PCI.
The findings were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
The study sought to explain the conflicting findings of previous trials investigating the efficacy of bivalirudin vs. heparin monotherapy. The VALIDATE-SWEDEHEART trial evaluated 6,006 patients who had PCI from June 2014 to September 2016, 90.3% via radial-artery access. This trial differed from previous studies because it was conducted after radial-artery access was routine and potent P2Y12 inhibitors were available, and earlier trials did not compare bivalirudin to heparin monotherapy, said David Erlinge, MD, PhD, of Lund (Sweden) University, and 38 coauthors (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1706443).
The Swedish investigators evaluated the primary endpoint – the composite of any-cause death, MI or major bleeding – during 180 days of follow-up. Among the study patients, 3,005 had ST-segment elevation MI (STEMI) and 3,001 non-STEMI (NSTEMI). All had undergone urgent PCI and most were also on P2Y inhibitors. The P2Y12 inhibitors used were ticagrelor in 5,697 patients (94.9%), prasugrel in 125 (2.1%) and cangrelor in 21 (0.3%).
Study patients with STEMI were permitted to receive up to 5,000 U of intravenous unfractionated heparin before arrival in the catheterization laboratory, and both STEMI and non-STEMI patients who had not received heparin previously could receive up to 3,000 U of intra-arterial heparin before angiography. All patients received aspirin pretreatment, and 62% received potent P2Y12 inhibitors at least one hour before PCI.
After angiography, but before PCI, patients were randomized 1:1 to receive in an open-label fashion either intravenous bivalirudin (The Medicines Company), or intra-arterial unfractionated heparin (LEO Pharma). Bivalirudin was administered as a bolus of 0.75 mg/kg of body weight followed by an infusion of 1.7 mg/kg per hour.
Research nurses contacted patients by phone 7 and 180 days after PCI. Baseline characteristics were similar between the bivalirudin and heparin groups. For example, around 31% of both groups had hyperlipidemia, and 15.2% of the bivalirudin group and 14.2% of the heparin group had a previous PCI.
“The rate of the primary endpoint did not differ significantly between the treatment groups at 30 days after PCI,” Dr. Erlinge and his coauthors noted. At 30 days, 7.2% of the bivalirudin patients and 8% of the heparin group had one of the primary endpoint outcomes, a nonsignificant difference. At 180 days, 12.3% of the bivalirudin group and 12.8% of those receiving heparin had one of the primary endpoint outcomes, also a nonsignificant difference.
Specific outcomes in the bivalirudin vs. heparin patients, respectively, at 180 days were: MI, 2% vs. 2.4%; major bleeding, 8.6% in both groups; stent thrombosis, 0.4% vs. 0.7%; and death from any cause, 2.9% vs. 2.8%, all nonsignificant differences.
“Results were consistent between patients with STEMI and those with NSTEMI and across all other prespecified subgroups,” the researchers wrote. They noted that women in the bivalirudin group had a lower, although not statistically significant, primary endpoint rate than did women in the heparin group.
In this trial, the high rate of radial-artery access and the low use of glycoprotein IIb/IIIa inhibitors may explain the low bleeding rates, the researchers said.
Among the study limitations were that patients excluded from the trial were at higher risk for a primary endpoint than those enrolled, the open-label design may have biased participating physicians in identifying outcomes, the telephone call-based follow-up may have been inherently unreliable, and the fact that most patients received a small dose of heparin before randomization may have reconciled any differences between the two drugs.
Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from Astra Zeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
FROM THE ESC CONGRESS 2017
Key clinical point: The rates of composite death, MI, or major bleeding for patients having PCI for MI were similar regardless of whether they received bivalirudin or heparin monotherapy.
Major finding: At 180 days, 12.3% of the bivalirudin patients and 12.8% of the heparin patients had one of the primary endpoint outcomes.
Data source: VALIDATE-SWEDEHEART, a registry-based, multicenter, randomized, controlled, open-label clinical trial of 6,006 patients who had PCI between June 2014 and September 2016.
Disclosure: Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from AstraZeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
C-section raises hysterectomy complication risk later
Women who have at least one cesarean delivery have a more than 30% risk of a complication requiring reoperation after benign hysterectomy later in life, compared with women who have had vaginal deliveries only, according to a study of more than 7,600 women in a Danish patient registry.
Cesarean delivery is the most common major surgery performed in the world, and the rate is rapidly increasing, with the global average cesarean rate estimated at 18.6%, and rates as high as 52% in some European countries. However, the impact cesarean deliveries have on surgical complications later in life has not been thoroughly studied. The study authors said this might be the first population study of the association of cesarean delivery with hysterectomy complications.
Of the 388 women (5%) who had a hysterectomy and then a reoperation within 30 days, the risk increased with the number of previous cesarean deliveries. Those who had vaginal-only deliveries had reoperation rates of 4.4%, compared with 6.2% for those who had one cesarean delivery and 6.8% for those who had two or more. That represents increased risks of 31% and 35% for women who had one cesarean delivery and two or more cesarean deliveries, respectively, compared with women who had only vaginal deliveries.
Likewise, surgical complications were 16% more frequent in women who had one previous cesarean delivery and 30% more likely in women with two or more cesarean deliveries. Women who had two or more cesarean deliveries were almost twice as likely (odds ratio, 1.93) to receive a blood transfusion.
“Our results imply that information on long-term associations should be made more readily available to women, clinicians, and policymakers and suggest that decisions on cesarean delivery should take into account not only immediate maternal and neonatal influences, but also women’s health in the long term, including an increased risk of reoperation and complications associated with surgery later in life,” the researchers wrote. “The results support policies and clinical efforts to prevent cesarean deliveries that are not medically indicated.”
The study noted some limitations, including the observational design, which did not allow for elimination of all potential confounding factors.
The researchers reported having no relevant financial disclosures.
Women who have at least one cesarean delivery have a more than 30% risk of a complication requiring reoperation after benign hysterectomy later in life, compared with women who have had vaginal deliveries only, according to a study of more than 7,600 women in a Danish patient registry.
Cesarean delivery is the most common major surgery performed in the world, and the rate is rapidly increasing, with the global average cesarean rate estimated at 18.6%, and rates as high as 52% in some European countries. However, the impact cesarean deliveries have on surgical complications later in life has not been thoroughly studied. The study authors said this might be the first population study of the association of cesarean delivery with hysterectomy complications.
Of the 388 women (5%) who had a hysterectomy and then a reoperation within 30 days, the risk increased with the number of previous cesarean deliveries. Those who had vaginal-only deliveries had reoperation rates of 4.4%, compared with 6.2% for those who had one cesarean delivery and 6.8% for those who had two or more. That represents increased risks of 31% and 35% for women who had one cesarean delivery and two or more cesarean deliveries, respectively, compared with women who had only vaginal deliveries.
Likewise, surgical complications were 16% more frequent in women who had one previous cesarean delivery and 30% more likely in women with two or more cesarean deliveries. Women who had two or more cesarean deliveries were almost twice as likely (odds ratio, 1.93) to receive a blood transfusion.
“Our results imply that information on long-term associations should be made more readily available to women, clinicians, and policymakers and suggest that decisions on cesarean delivery should take into account not only immediate maternal and neonatal influences, but also women’s health in the long term, including an increased risk of reoperation and complications associated with surgery later in life,” the researchers wrote. “The results support policies and clinical efforts to prevent cesarean deliveries that are not medically indicated.”
The study noted some limitations, including the observational design, which did not allow for elimination of all potential confounding factors.
The researchers reported having no relevant financial disclosures.
Women who have at least one cesarean delivery have a more than 30% risk of a complication requiring reoperation after benign hysterectomy later in life, compared with women who have had vaginal deliveries only, according to a study of more than 7,600 women in a Danish patient registry.
Cesarean delivery is the most common major surgery performed in the world, and the rate is rapidly increasing, with the global average cesarean rate estimated at 18.6%, and rates as high as 52% in some European countries. However, the impact cesarean deliveries have on surgical complications later in life has not been thoroughly studied. The study authors said this might be the first population study of the association of cesarean delivery with hysterectomy complications.
Of the 388 women (5%) who had a hysterectomy and then a reoperation within 30 days, the risk increased with the number of previous cesarean deliveries. Those who had vaginal-only deliveries had reoperation rates of 4.4%, compared with 6.2% for those who had one cesarean delivery and 6.8% for those who had two or more. That represents increased risks of 31% and 35% for women who had one cesarean delivery and two or more cesarean deliveries, respectively, compared with women who had only vaginal deliveries.
Likewise, surgical complications were 16% more frequent in women who had one previous cesarean delivery and 30% more likely in women with two or more cesarean deliveries. Women who had two or more cesarean deliveries were almost twice as likely (odds ratio, 1.93) to receive a blood transfusion.
“Our results imply that information on long-term associations should be made more readily available to women, clinicians, and policymakers and suggest that decisions on cesarean delivery should take into account not only immediate maternal and neonatal influences, but also women’s health in the long term, including an increased risk of reoperation and complications associated with surgery later in life,” the researchers wrote. “The results support policies and clinical efforts to prevent cesarean deliveries that are not medically indicated.”
The study noted some limitations, including the observational design, which did not allow for elimination of all potential confounding factors.
The researchers reported having no relevant financial disclosures.
FROM JAMA SURGERY
Key clinical point:
Major finding: The rate of complications after hysterectomy was 4.4% for women who had vaginal birth only, 6.2% for those who had one cesarean delivery, and 6.8% for those who had two or more cesarean deliveries.
Data source: Danish National Patient Registry–based cohort study of 7,685 women who gave birth from 1993 to 2012.
Disclosures: The researchers reported having no financial disclosures.
Malperfusion key in aortic dissection repair outcomes
Early repair is the standard of care for patients with type A aortic dissection, but the presence of malperfusion rather than the timing of surgery may be a major determinant in patient survival both in the hospital and in the long term, according to an analysis of patients with acute type A aortic dissection over a 17-year period at the University of Bristol (England).
“Malperfusion at presentation rather than the timing of intervention is the major risk factor for death in both the short term and long term in patients undergoing surgical repair of type A aortic dissection,” Pradeep Narayan, FRCS, and his colleagues said in reporting their findings in the July issue of the Journal of Thoracic and Cardiovascular Surgery (154:81-6). Nonetheless, Dr. Narayan and his colleagues acknowledged that early operation prevents the development of malperfusion and is the best option for restoring normal perfusion for patients who already have malperfusion.
Their study analyzed results from two different groups of patients who had surgery for repair of acute type A aortic dissection over a 17-year period: 72 in the early surgery group that had operative repair within 12 hours of symptom onset; and 80 in the late-surgery group that had the operation 12 hours or more after symptoms first appeared. A total of 205 patients underwent surgical repair for acute type A aortic dissection in that period, but only 152 cases had recorded the timing of surgery from onset of symptoms. The median time between arrival at the center and surgery was 3 hours.
Dr. Narayan and his coauthors reported that 39% (60) of the 152 patients had malperfusion. Organ malperfusion was actually more common in the early surgery group, although the difference was not significant: 48.6% vs. 31.3% in the late-surgery group (P = .29). Early mortality was also similar between the two groups: 19.4% in the early surgery group and 13.8% in the late surgery group (P = .8). In terms of late survival, the study found no difference between the two groups.
Dr. Narayan and his coauthors reported that malperfusion and concomitant coronary artery bypass grafting were independent predictors of survival, with hazard ratios of 2.65 (P = .01) and 3.03 (P = .03), respectively. As a nonlinear variable, time to surgery showed an inverse relationship with late mortality (HR, 0.51; P = .26), but as a linear variable when adjusted for other covariates, including malperfusion, it did not affect survival (HR, 1.01; P = .09).
“The main finding of the present study is that almost 40% of patients undergoing repair of type A aortic dissection had evidence of malperfusion,” Dr. Narayan and his coauthors said. “The second important finding is that the presence of malperfusion was associated with significantly increased risk of death in both the short-term and long-term follow-up.” While a delayed operation was associated with a reduced risk of death, it was not significant when accounting for malperfusion.
Dr. Narayan and his coauthors acknowledged limitations of their study, the most important of which was the including of different types of malperfusion as a single variable. Also, the small sample size may explain the lack of statistically significant differences between the two groups.
Dr. Narayan and his coauthors had no financial relationships to disclose.
Malperfusion has the potential to serve as a marker for the need for surgery in type A aortic dissection, but the inability to identify the true risk of developing malperfusion in the first 12-24 hours after acute type A dissection means that the indication for early surgery will remain unchanged, James I. Fann, MD, of Stanford (Calif.) University says in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:87-8).
“The findings of Narayan and colleagues impel us to review the history of the development of the classification and treatment (or in fact vice versa) of acute type A dissection and to acknowledge that early timing of surgery in these high-risk patients was originally proposed to prevent malperfusion and to respond to the most catastrophic complications,” Dr. Fann said.
But Dr. Fann cautioned against “being dismissive” of their findings, because such questioning and re-evaluation are essential in developing appropriate treatments. “Now, the question is whether we can identify the cohort of patients who are at lower risk for the development of malperfusion and tailor their treatment,” he said.
Dr. Fann had no financial relationships to disclose.
Malperfusion has the potential to serve as a marker for the need for surgery in type A aortic dissection, but the inability to identify the true risk of developing malperfusion in the first 12-24 hours after acute type A dissection means that the indication for early surgery will remain unchanged, James I. Fann, MD, of Stanford (Calif.) University says in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:87-8).
“The findings of Narayan and colleagues impel us to review the history of the development of the classification and treatment (or in fact vice versa) of acute type A dissection and to acknowledge that early timing of surgery in these high-risk patients was originally proposed to prevent malperfusion and to respond to the most catastrophic complications,” Dr. Fann said.
But Dr. Fann cautioned against “being dismissive” of their findings, because such questioning and re-evaluation are essential in developing appropriate treatments. “Now, the question is whether we can identify the cohort of patients who are at lower risk for the development of malperfusion and tailor their treatment,” he said.
Dr. Fann had no financial relationships to disclose.
Malperfusion has the potential to serve as a marker for the need for surgery in type A aortic dissection, but the inability to identify the true risk of developing malperfusion in the first 12-24 hours after acute type A dissection means that the indication for early surgery will remain unchanged, James I. Fann, MD, of Stanford (Calif.) University says in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:87-8).
“The findings of Narayan and colleagues impel us to review the history of the development of the classification and treatment (or in fact vice versa) of acute type A dissection and to acknowledge that early timing of surgery in these high-risk patients was originally proposed to prevent malperfusion and to respond to the most catastrophic complications,” Dr. Fann said.
But Dr. Fann cautioned against “being dismissive” of their findings, because such questioning and re-evaluation are essential in developing appropriate treatments. “Now, the question is whether we can identify the cohort of patients who are at lower risk for the development of malperfusion and tailor their treatment,” he said.
Dr. Fann had no financial relationships to disclose.
Early repair is the standard of care for patients with type A aortic dissection, but the presence of malperfusion rather than the timing of surgery may be a major determinant in patient survival both in the hospital and in the long term, according to an analysis of patients with acute type A aortic dissection over a 17-year period at the University of Bristol (England).
“Malperfusion at presentation rather than the timing of intervention is the major risk factor for death in both the short term and long term in patients undergoing surgical repair of type A aortic dissection,” Pradeep Narayan, FRCS, and his colleagues said in reporting their findings in the July issue of the Journal of Thoracic and Cardiovascular Surgery (154:81-6). Nonetheless, Dr. Narayan and his colleagues acknowledged that early operation prevents the development of malperfusion and is the best option for restoring normal perfusion for patients who already have malperfusion.
Their study analyzed results from two different groups of patients who had surgery for repair of acute type A aortic dissection over a 17-year period: 72 in the early surgery group that had operative repair within 12 hours of symptom onset; and 80 in the late-surgery group that had the operation 12 hours or more after symptoms first appeared. A total of 205 patients underwent surgical repair for acute type A aortic dissection in that period, but only 152 cases had recorded the timing of surgery from onset of symptoms. The median time between arrival at the center and surgery was 3 hours.
Dr. Narayan and his coauthors reported that 39% (60) of the 152 patients had malperfusion. Organ malperfusion was actually more common in the early surgery group, although the difference was not significant: 48.6% vs. 31.3% in the late-surgery group (P = .29). Early mortality was also similar between the two groups: 19.4% in the early surgery group and 13.8% in the late surgery group (P = .8). In terms of late survival, the study found no difference between the two groups.
Dr. Narayan and his coauthors reported that malperfusion and concomitant coronary artery bypass grafting were independent predictors of survival, with hazard ratios of 2.65 (P = .01) and 3.03 (P = .03), respectively. As a nonlinear variable, time to surgery showed an inverse relationship with late mortality (HR, 0.51; P = .26), but as a linear variable when adjusted for other covariates, including malperfusion, it did not affect survival (HR, 1.01; P = .09).
“The main finding of the present study is that almost 40% of patients undergoing repair of type A aortic dissection had evidence of malperfusion,” Dr. Narayan and his coauthors said. “The second important finding is that the presence of malperfusion was associated with significantly increased risk of death in both the short-term and long-term follow-up.” While a delayed operation was associated with a reduced risk of death, it was not significant when accounting for malperfusion.
Dr. Narayan and his coauthors acknowledged limitations of their study, the most important of which was the including of different types of malperfusion as a single variable. Also, the small sample size may explain the lack of statistically significant differences between the two groups.
Dr. Narayan and his coauthors had no financial relationships to disclose.
Early repair is the standard of care for patients with type A aortic dissection, but the presence of malperfusion rather than the timing of surgery may be a major determinant in patient survival both in the hospital and in the long term, according to an analysis of patients with acute type A aortic dissection over a 17-year period at the University of Bristol (England).
“Malperfusion at presentation rather than the timing of intervention is the major risk factor for death in both the short term and long term in patients undergoing surgical repair of type A aortic dissection,” Pradeep Narayan, FRCS, and his colleagues said in reporting their findings in the July issue of the Journal of Thoracic and Cardiovascular Surgery (154:81-6). Nonetheless, Dr. Narayan and his colleagues acknowledged that early operation prevents the development of malperfusion and is the best option for restoring normal perfusion for patients who already have malperfusion.
Their study analyzed results from two different groups of patients who had surgery for repair of acute type A aortic dissection over a 17-year period: 72 in the early surgery group that had operative repair within 12 hours of symptom onset; and 80 in the late-surgery group that had the operation 12 hours or more after symptoms first appeared. A total of 205 patients underwent surgical repair for acute type A aortic dissection in that period, but only 152 cases had recorded the timing of surgery from onset of symptoms. The median time between arrival at the center and surgery was 3 hours.
Dr. Narayan and his coauthors reported that 39% (60) of the 152 patients had malperfusion. Organ malperfusion was actually more common in the early surgery group, although the difference was not significant: 48.6% vs. 31.3% in the late-surgery group (P = .29). Early mortality was also similar between the two groups: 19.4% in the early surgery group and 13.8% in the late surgery group (P = .8). In terms of late survival, the study found no difference between the two groups.
Dr. Narayan and his coauthors reported that malperfusion and concomitant coronary artery bypass grafting were independent predictors of survival, with hazard ratios of 2.65 (P = .01) and 3.03 (P = .03), respectively. As a nonlinear variable, time to surgery showed an inverse relationship with late mortality (HR, 0.51; P = .26), but as a linear variable when adjusted for other covariates, including malperfusion, it did not affect survival (HR, 1.01; P = .09).
“The main finding of the present study is that almost 40% of patients undergoing repair of type A aortic dissection had evidence of malperfusion,” Dr. Narayan and his coauthors said. “The second important finding is that the presence of malperfusion was associated with significantly increased risk of death in both the short-term and long-term follow-up.” While a delayed operation was associated with a reduced risk of death, it was not significant when accounting for malperfusion.
Dr. Narayan and his coauthors acknowledged limitations of their study, the most important of which was the including of different types of malperfusion as a single variable. Also, the small sample size may explain the lack of statistically significant differences between the two groups.
Dr. Narayan and his coauthors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Malperfusion is a main determinant of outcomes for patients having surgical repair for acute type A aortic dissection.
Major finding: Patients in the early surgery group (surgery within 12 hours of onset) were more likely to have malperfusion than those who had surgery later, 47% vs. 31%.
Data source: Single-center analysis of 152 operations for repair of acute type A aortic dissections over a 17-year period.
Disclosures: Dr. Narayan and his coauthors had no financial relationships to disclose.