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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.
Recovery: Where TAVR gains advantage over SAVR
A post hoc analysis of the first randomized clinical to show the superiority of an interventional technique for aortic valve repair over surgery in terms of postoperative death has found the period of 30 days to 4 months after the procedure to be the most perilous for surgery patients, when their risk of death was almost twice that of interventional patients, likely because surgery patients were more vulnerable to complications and were less likely to go home after the procedure.
“This mortality difference was largely driven by higher rates of technical failure, surgical complications, and lack of recovery following surgery,” said Vincent A. Gaudiani, MD, of El Camino Hospital, Mountain View, Calif., and his coauthors (J Thorac Cardiovasc Surg. 2017;153:1293-99). The analysis investigated causes and timing of death in the CoreValve US Pivotal High-Risk Trial, a randomized, high-risk trial of the CoreValve self-expanding bioprosthesis (Medtronic). The trial favored transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR).
The post hoc analysis evaluated all-cause mortality through the first year based on three time periods: early, up to 30 days; recovery, 31-120 days; and late, 121-365 days. Death rates for the two procedures were similar in the early and late postoperative periods, but deviated significantly in the recovery period: 4% for TAVR vs. 7.9% for SAVR (P = .25). SAVR patients were more likely affected by the overall influence of physical stress associated with surgery, the study found, whereas rates of technical failure and complications were similar between the two groups. “This suggests that early TAVR results can improve with technical refinements and that high-risk surgical patients will benefit from reducing complications,” wrote Dr. Gaudiani and his coauthors.
They noted the CoreValve trial findings, in terms of the survival differences between TAVR and SAVR, are significant because previous trials that compared TAVR and SAVR, including the Placement of Aortic Transcatheter Valves A trial (Lancet. 2015;385:2477-84), showed equivalent survival between the two procedures at up to 5 years. “This unique finding is provocative and the reason for this survival difference is important to understanding TAVR and SAVR and improving both therapies,” said Dr. Gaudiani and his coauthors.
While SAVR patients had a higher overall death rate in the recovery period, TAVR patients had a larger proportion of cardiovascular deaths – 12 of 15 (80%) vs. 16 of 27 (59.3%) for SAVR. The leading noncardiovascular cause of death in the SAVR group was sepsis (six), followed by malignancy (one), chronic obstructive pulmonary disease (one) and other (three). “Although these deaths were adjudicated as noncardiovascular by the CEC [clinical events committee], our review showed that some of these patients had never really recovered from the initial procedure,” the researchers wrote.
In the early period, death rates were 3.3% for TAVR and 4.5% for SAVR, a nonsignificant difference. TAVR patients who died had higher rates of peripheral vascular disease and recent falls; SAVR patients who died were more likely to have had a pacemaker. In the late period, the death rates were 7.5% for TAVR and 7.7% for SAVR, and the researchers also found no significant difference in the number of cardiovascular deaths (4.4% and 4.2%, respectively). “Hierarchical causes of death were primarily due to other reasons deemed unrelated to the initial aortic valve replacement,” noted Dr. Gaudiani and his coauthors.
However, the study also found that TAVR patients were significantly more likely to go home after hospital discharge rather than to a rehabilitation facility or another hospital – 66.9% vs. 39.7% (P less than .001).
In the SAVR group, five cardiovascular deaths in the recovery period occurred because the operation failed to correct aortic stenosis – all related to placement of a valve too small for the patient. “Placing a valve appropriately sized to the patient should be a priority for surgeons if we are to improve our outcomes,” the researchers noted. “Most other deaths were the result of patients’ inability to cope with the physical trauma of surgery.”
Dr. Gaudiani disclosed that he is a consultant and paid instructor for Medtronic, St. Jude Medical, and Edwards Lifesciences. Coauthors disclosed relationships with Edwards Lifesciences, Terumo, Gore Medical, Medtronic, Boston Scientific, and other device companies.
In his invited discussion, Craig R. Smith, MD, of New York, noted that comparisons “are odious” and that comparing clinical trials requires caution. (J Thorac Cardiovasc Surg. 2017;153:1300-1) He also acknowledged that surgeons would hope for evidence that the findings of the CoreValve US Pivotal High-Risk Trial were somehow wrong.
Dr. Smith raised a question about the CoreValve trial, which was designed to enroll high-risk patients, “but actually enrolled at the upper end of the intermediate risk range with a Society of Thoracic Surgeons (STS) score of 7.4 versus 11.3 in the high-risk PARTNER 1.” However, he noted that it would not be fair to consider the self-expanding TAVR trial intermediate risk, because the intermediate risk PARTNER 2 trial had an STS score of 5.8. And while outcomes for SAVR in the CoreValve trial were within the expected variable of less than 1 using the STS Predicted Risk for Mortality, the “bulge” of deaths in the recovery phase raises “a whiff of concern.”
Dr. Smith said that the early technical mortalities with TAVR in the trial are already disappearing with experience. He also noted that Dr. Gaudiani and his coauthors pointed out the frequency of failure to repair and failure to recover. “Whether competing against TAVR in a randomized trial or operating on TAVR in eligible patients in the future, as the authors have emphasized, it behooves us to correct the problem as completely as possible and take the best possible care of our patients afterward,” Dr. Smith said. He also noted the difference in discharge rates home “illustrates a very significant advantage of TAVR.”
Dr. Smith disclosed he has received reimbursement for expenses in his leadership role in the Placement of Aortic Transcatheter Valves (PARTNER) trials.
In his invited discussion, Craig R. Smith, MD, of New York, noted that comparisons “are odious” and that comparing clinical trials requires caution. (J Thorac Cardiovasc Surg. 2017;153:1300-1) He also acknowledged that surgeons would hope for evidence that the findings of the CoreValve US Pivotal High-Risk Trial were somehow wrong.
Dr. Smith raised a question about the CoreValve trial, which was designed to enroll high-risk patients, “but actually enrolled at the upper end of the intermediate risk range with a Society of Thoracic Surgeons (STS) score of 7.4 versus 11.3 in the high-risk PARTNER 1.” However, he noted that it would not be fair to consider the self-expanding TAVR trial intermediate risk, because the intermediate risk PARTNER 2 trial had an STS score of 5.8. And while outcomes for SAVR in the CoreValve trial were within the expected variable of less than 1 using the STS Predicted Risk for Mortality, the “bulge” of deaths in the recovery phase raises “a whiff of concern.”
Dr. Smith said that the early technical mortalities with TAVR in the trial are already disappearing with experience. He also noted that Dr. Gaudiani and his coauthors pointed out the frequency of failure to repair and failure to recover. “Whether competing against TAVR in a randomized trial or operating on TAVR in eligible patients in the future, as the authors have emphasized, it behooves us to correct the problem as completely as possible and take the best possible care of our patients afterward,” Dr. Smith said. He also noted the difference in discharge rates home “illustrates a very significant advantage of TAVR.”
Dr. Smith disclosed he has received reimbursement for expenses in his leadership role in the Placement of Aortic Transcatheter Valves (PARTNER) trials.
In his invited discussion, Craig R. Smith, MD, of New York, noted that comparisons “are odious” and that comparing clinical trials requires caution. (J Thorac Cardiovasc Surg. 2017;153:1300-1) He also acknowledged that surgeons would hope for evidence that the findings of the CoreValve US Pivotal High-Risk Trial were somehow wrong.
Dr. Smith raised a question about the CoreValve trial, which was designed to enroll high-risk patients, “but actually enrolled at the upper end of the intermediate risk range with a Society of Thoracic Surgeons (STS) score of 7.4 versus 11.3 in the high-risk PARTNER 1.” However, he noted that it would not be fair to consider the self-expanding TAVR trial intermediate risk, because the intermediate risk PARTNER 2 trial had an STS score of 5.8. And while outcomes for SAVR in the CoreValve trial were within the expected variable of less than 1 using the STS Predicted Risk for Mortality, the “bulge” of deaths in the recovery phase raises “a whiff of concern.”
Dr. Smith said that the early technical mortalities with TAVR in the trial are already disappearing with experience. He also noted that Dr. Gaudiani and his coauthors pointed out the frequency of failure to repair and failure to recover. “Whether competing against TAVR in a randomized trial or operating on TAVR in eligible patients in the future, as the authors have emphasized, it behooves us to correct the problem as completely as possible and take the best possible care of our patients afterward,” Dr. Smith said. He also noted the difference in discharge rates home “illustrates a very significant advantage of TAVR.”
Dr. Smith disclosed he has received reimbursement for expenses in his leadership role in the Placement of Aortic Transcatheter Valves (PARTNER) trials.
A post hoc analysis of the first randomized clinical to show the superiority of an interventional technique for aortic valve repair over surgery in terms of postoperative death has found the period of 30 days to 4 months after the procedure to be the most perilous for surgery patients, when their risk of death was almost twice that of interventional patients, likely because surgery patients were more vulnerable to complications and were less likely to go home after the procedure.
“This mortality difference was largely driven by higher rates of technical failure, surgical complications, and lack of recovery following surgery,” said Vincent A. Gaudiani, MD, of El Camino Hospital, Mountain View, Calif., and his coauthors (J Thorac Cardiovasc Surg. 2017;153:1293-99). The analysis investigated causes and timing of death in the CoreValve US Pivotal High-Risk Trial, a randomized, high-risk trial of the CoreValve self-expanding bioprosthesis (Medtronic). The trial favored transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR).
The post hoc analysis evaluated all-cause mortality through the first year based on three time periods: early, up to 30 days; recovery, 31-120 days; and late, 121-365 days. Death rates for the two procedures were similar in the early and late postoperative periods, but deviated significantly in the recovery period: 4% for TAVR vs. 7.9% for SAVR (P = .25). SAVR patients were more likely affected by the overall influence of physical stress associated with surgery, the study found, whereas rates of technical failure and complications were similar between the two groups. “This suggests that early TAVR results can improve with technical refinements and that high-risk surgical patients will benefit from reducing complications,” wrote Dr. Gaudiani and his coauthors.
They noted the CoreValve trial findings, in terms of the survival differences between TAVR and SAVR, are significant because previous trials that compared TAVR and SAVR, including the Placement of Aortic Transcatheter Valves A trial (Lancet. 2015;385:2477-84), showed equivalent survival between the two procedures at up to 5 years. “This unique finding is provocative and the reason for this survival difference is important to understanding TAVR and SAVR and improving both therapies,” said Dr. Gaudiani and his coauthors.
While SAVR patients had a higher overall death rate in the recovery period, TAVR patients had a larger proportion of cardiovascular deaths – 12 of 15 (80%) vs. 16 of 27 (59.3%) for SAVR. The leading noncardiovascular cause of death in the SAVR group was sepsis (six), followed by malignancy (one), chronic obstructive pulmonary disease (one) and other (three). “Although these deaths were adjudicated as noncardiovascular by the CEC [clinical events committee], our review showed that some of these patients had never really recovered from the initial procedure,” the researchers wrote.
In the early period, death rates were 3.3% for TAVR and 4.5% for SAVR, a nonsignificant difference. TAVR patients who died had higher rates of peripheral vascular disease and recent falls; SAVR patients who died were more likely to have had a pacemaker. In the late period, the death rates were 7.5% for TAVR and 7.7% for SAVR, and the researchers also found no significant difference in the number of cardiovascular deaths (4.4% and 4.2%, respectively). “Hierarchical causes of death were primarily due to other reasons deemed unrelated to the initial aortic valve replacement,” noted Dr. Gaudiani and his coauthors.
However, the study also found that TAVR patients were significantly more likely to go home after hospital discharge rather than to a rehabilitation facility or another hospital – 66.9% vs. 39.7% (P less than .001).
In the SAVR group, five cardiovascular deaths in the recovery period occurred because the operation failed to correct aortic stenosis – all related to placement of a valve too small for the patient. “Placing a valve appropriately sized to the patient should be a priority for surgeons if we are to improve our outcomes,” the researchers noted. “Most other deaths were the result of patients’ inability to cope with the physical trauma of surgery.”
Dr. Gaudiani disclosed that he is a consultant and paid instructor for Medtronic, St. Jude Medical, and Edwards Lifesciences. Coauthors disclosed relationships with Edwards Lifesciences, Terumo, Gore Medical, Medtronic, Boston Scientific, and other device companies.
A post hoc analysis of the first randomized clinical to show the superiority of an interventional technique for aortic valve repair over surgery in terms of postoperative death has found the period of 30 days to 4 months after the procedure to be the most perilous for surgery patients, when their risk of death was almost twice that of interventional patients, likely because surgery patients were more vulnerable to complications and were less likely to go home after the procedure.
“This mortality difference was largely driven by higher rates of technical failure, surgical complications, and lack of recovery following surgery,” said Vincent A. Gaudiani, MD, of El Camino Hospital, Mountain View, Calif., and his coauthors (J Thorac Cardiovasc Surg. 2017;153:1293-99). The analysis investigated causes and timing of death in the CoreValve US Pivotal High-Risk Trial, a randomized, high-risk trial of the CoreValve self-expanding bioprosthesis (Medtronic). The trial favored transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR).
The post hoc analysis evaluated all-cause mortality through the first year based on three time periods: early, up to 30 days; recovery, 31-120 days; and late, 121-365 days. Death rates for the two procedures were similar in the early and late postoperative periods, but deviated significantly in the recovery period: 4% for TAVR vs. 7.9% for SAVR (P = .25). SAVR patients were more likely affected by the overall influence of physical stress associated with surgery, the study found, whereas rates of technical failure and complications were similar between the two groups. “This suggests that early TAVR results can improve with technical refinements and that high-risk surgical patients will benefit from reducing complications,” wrote Dr. Gaudiani and his coauthors.
They noted the CoreValve trial findings, in terms of the survival differences between TAVR and SAVR, are significant because previous trials that compared TAVR and SAVR, including the Placement of Aortic Transcatheter Valves A trial (Lancet. 2015;385:2477-84), showed equivalent survival between the two procedures at up to 5 years. “This unique finding is provocative and the reason for this survival difference is important to understanding TAVR and SAVR and improving both therapies,” said Dr. Gaudiani and his coauthors.
While SAVR patients had a higher overall death rate in the recovery period, TAVR patients had a larger proportion of cardiovascular deaths – 12 of 15 (80%) vs. 16 of 27 (59.3%) for SAVR. The leading noncardiovascular cause of death in the SAVR group was sepsis (six), followed by malignancy (one), chronic obstructive pulmonary disease (one) and other (three). “Although these deaths were adjudicated as noncardiovascular by the CEC [clinical events committee], our review showed that some of these patients had never really recovered from the initial procedure,” the researchers wrote.
In the early period, death rates were 3.3% for TAVR and 4.5% for SAVR, a nonsignificant difference. TAVR patients who died had higher rates of peripheral vascular disease and recent falls; SAVR patients who died were more likely to have had a pacemaker. In the late period, the death rates were 7.5% for TAVR and 7.7% for SAVR, and the researchers also found no significant difference in the number of cardiovascular deaths (4.4% and 4.2%, respectively). “Hierarchical causes of death were primarily due to other reasons deemed unrelated to the initial aortic valve replacement,” noted Dr. Gaudiani and his coauthors.
However, the study also found that TAVR patients were significantly more likely to go home after hospital discharge rather than to a rehabilitation facility or another hospital – 66.9% vs. 39.7% (P less than .001).
In the SAVR group, five cardiovascular deaths in the recovery period occurred because the operation failed to correct aortic stenosis – all related to placement of a valve too small for the patient. “Placing a valve appropriately sized to the patient should be a priority for surgeons if we are to improve our outcomes,” the researchers noted. “Most other deaths were the result of patients’ inability to cope with the physical trauma of surgery.”
Dr. Gaudiani disclosed that he is a consultant and paid instructor for Medtronic, St. Jude Medical, and Edwards Lifesciences. Coauthors disclosed relationships with Edwards Lifesciences, Terumo, Gore Medical, Medtronic, Boston Scientific, and other device companies.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Differences in survival between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in high-risk patients appear to be driven primarily by issues with disease repair and patient recovery from SAVR.
Major finding: During the recovery period (31-120 days) the death rate was 4% for TAVR vs. 7.9% for SAVR (P = .025).
Data source: Post hoc analysis of CoreValve US Pivotal High-Risk Trial involving 750 patients and 45 sites with outcomes reported through 3 years.
Disclosures: Dr. Gaudiani disclosed that he is a consultant and paid instructor for Medtronic, St. Jude Medical, and Edwards Lifesciences. Coauthors disclosed relationships with Edwards Lifesciences, Terumo, Gore Medical, Medtronic, Boston Scientific, and other device companies.
New trial shows thymectomy benefits myasthenia gravis
The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).
The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.
Those markers include an average quantitative myasthenia score of 6.15 for the thymectomy group vs. 8.99 for the medical therapy group (P less than .0001); a lower dose of prednisone to attain improved neurologic status (44 mg vs. 60 mg; P less than .001); time-weighted average score on the Myasthenia Gravis Activities of Daily Living scale (2.24 vs. 3.41; P = .008); azathioprine use (17% vs. 48%; P less than .001); percentage of patients who had minimal-manifestation status at month 36 (67% vs. 47%; P = .03); and hospitalization for myasthenia-related symptoms (9% vs. 37%). “Interestingly,” the researchers wrote, “despite these quantitative results, no difference was seen in the quality of life measured surveys.”
An ancillary study, Bio-MGTX, was performed simultaneously to investigate pathologic and serum markers. “Many questions still need to be answered in regard to the role of thymectomy in MG,” Dr. Sonett and his coauthors maintained. They include an analysis of radiologic predictors of success with thymectomy, and the role of thymectomy in seronegative MG, ocular MG and elderly patients.
“Future studies may be directed at achieving a more rapid and consistent time to a complete symptom response,” they said.
The MGTX trial does support the use of high-dose prednisone induction combined with thymectomy to achieve higher complete early remission rates, but Bio-MGTX data may help to refine induction protocols. “The debate will likely continue in regard to widespread adoption of extended transsternal maximal thymectomy,” the researchers wrote. “What was categorically measured in this trial was the effect of maximal thymectomy, as sternotomy offers no particular independent therapeutic benefit.”
The structure of the MGTX trial despite its small cohort (126) “enabled the medical and surgical community to definitively answer an important question,” they noted. Nonetheless, further investigation of the role of thymectomy in MG is “sorely needed.”
Patients may need up to 3 years to achieve an optimal response, and complete cure in a shorter time frame should be the goal for each patient. Multimodal therapy should be the basis of MG treatment. “Continued progress in the management of MG will require diligent, multidisciplinary teams designing and completing prospective studies like the MGTX,” the researchers wrote.
Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
In the MGTX trial, patients in the thymectomy group still needed a high average dose of prednisone, and the rates of remission may decrease over time, Michael K. Hsin, MD, of Queen Mary Hospital, Hong Kong, wrote in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:310-1). But he added that the trial did finally answer in a positive manner whether thymectomy could serve a beneficial role.
He also noted that the MGTX trial left at least four questions unanswered:
• The long-term effect of thymectomy on MG status with regard to future relapse.
• The role of surgery in the era of advances in medical treatment, including azathioprine to reduce the prednisone dose and emergence of stem-cell transplantation.
• The extent to which MGTX findings can be applied to acetylcholine receptor-negative pediatric patients.
• Whether alternative techniques to extended transsternal thymectomy can achieve comparable results.
Dr. Hsin had no financial relationships to disclose.
In the MGTX trial, patients in the thymectomy group still needed a high average dose of prednisone, and the rates of remission may decrease over time, Michael K. Hsin, MD, of Queen Mary Hospital, Hong Kong, wrote in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:310-1). But he added that the trial did finally answer in a positive manner whether thymectomy could serve a beneficial role.
He also noted that the MGTX trial left at least four questions unanswered:
• The long-term effect of thymectomy on MG status with regard to future relapse.
• The role of surgery in the era of advances in medical treatment, including azathioprine to reduce the prednisone dose and emergence of stem-cell transplantation.
• The extent to which MGTX findings can be applied to acetylcholine receptor-negative pediatric patients.
• Whether alternative techniques to extended transsternal thymectomy can achieve comparable results.
Dr. Hsin had no financial relationships to disclose.
In the MGTX trial, patients in the thymectomy group still needed a high average dose of prednisone, and the rates of remission may decrease over time, Michael K. Hsin, MD, of Queen Mary Hospital, Hong Kong, wrote in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:310-1). But he added that the trial did finally answer in a positive manner whether thymectomy could serve a beneficial role.
He also noted that the MGTX trial left at least four questions unanswered:
• The long-term effect of thymectomy on MG status with regard to future relapse.
• The role of surgery in the era of advances in medical treatment, including azathioprine to reduce the prednisone dose and emergence of stem-cell transplantation.
• The extent to which MGTX findings can be applied to acetylcholine receptor-negative pediatric patients.
• Whether alternative techniques to extended transsternal thymectomy can achieve comparable results.
Dr. Hsin had no financial relationships to disclose.
The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).
The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.
Those markers include an average quantitative myasthenia score of 6.15 for the thymectomy group vs. 8.99 for the medical therapy group (P less than .0001); a lower dose of prednisone to attain improved neurologic status (44 mg vs. 60 mg; P less than .001); time-weighted average score on the Myasthenia Gravis Activities of Daily Living scale (2.24 vs. 3.41; P = .008); azathioprine use (17% vs. 48%; P less than .001); percentage of patients who had minimal-manifestation status at month 36 (67% vs. 47%; P = .03); and hospitalization for myasthenia-related symptoms (9% vs. 37%). “Interestingly,” the researchers wrote, “despite these quantitative results, no difference was seen in the quality of life measured surveys.”
An ancillary study, Bio-MGTX, was performed simultaneously to investigate pathologic and serum markers. “Many questions still need to be answered in regard to the role of thymectomy in MG,” Dr. Sonett and his coauthors maintained. They include an analysis of radiologic predictors of success with thymectomy, and the role of thymectomy in seronegative MG, ocular MG and elderly patients.
“Future studies may be directed at achieving a more rapid and consistent time to a complete symptom response,” they said.
The MGTX trial does support the use of high-dose prednisone induction combined with thymectomy to achieve higher complete early remission rates, but Bio-MGTX data may help to refine induction protocols. “The debate will likely continue in regard to widespread adoption of extended transsternal maximal thymectomy,” the researchers wrote. “What was categorically measured in this trial was the effect of maximal thymectomy, as sternotomy offers no particular independent therapeutic benefit.”
The structure of the MGTX trial despite its small cohort (126) “enabled the medical and surgical community to definitively answer an important question,” they noted. Nonetheless, further investigation of the role of thymectomy in MG is “sorely needed.”
Patients may need up to 3 years to achieve an optimal response, and complete cure in a shorter time frame should be the goal for each patient. Multimodal therapy should be the basis of MG treatment. “Continued progress in the management of MG will require diligent, multidisciplinary teams designing and completing prospective studies like the MGTX,” the researchers wrote.
Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).
The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.
Those markers include an average quantitative myasthenia score of 6.15 for the thymectomy group vs. 8.99 for the medical therapy group (P less than .0001); a lower dose of prednisone to attain improved neurologic status (44 mg vs. 60 mg; P less than .001); time-weighted average score on the Myasthenia Gravis Activities of Daily Living scale (2.24 vs. 3.41; P = .008); azathioprine use (17% vs. 48%; P less than .001); percentage of patients who had minimal-manifestation status at month 36 (67% vs. 47%; P = .03); and hospitalization for myasthenia-related symptoms (9% vs. 37%). “Interestingly,” the researchers wrote, “despite these quantitative results, no difference was seen in the quality of life measured surveys.”
An ancillary study, Bio-MGTX, was performed simultaneously to investigate pathologic and serum markers. “Many questions still need to be answered in regard to the role of thymectomy in MG,” Dr. Sonett and his coauthors maintained. They include an analysis of radiologic predictors of success with thymectomy, and the role of thymectomy in seronegative MG, ocular MG and elderly patients.
“Future studies may be directed at achieving a more rapid and consistent time to a complete symptom response,” they said.
The MGTX trial does support the use of high-dose prednisone induction combined with thymectomy to achieve higher complete early remission rates, but Bio-MGTX data may help to refine induction protocols. “The debate will likely continue in regard to widespread adoption of extended transsternal maximal thymectomy,” the researchers wrote. “What was categorically measured in this trial was the effect of maximal thymectomy, as sternotomy offers no particular independent therapeutic benefit.”
The structure of the MGTX trial despite its small cohort (126) “enabled the medical and surgical community to definitively answer an important question,” they noted. Nonetheless, further investigation of the role of thymectomy in MG is “sorely needed.”
Patients may need up to 3 years to achieve an optimal response, and complete cure in a shorter time frame should be the goal for each patient. Multimodal therapy should be the basis of MG treatment. “Continued progress in the management of MG will require diligent, multidisciplinary teams designing and completing prospective studies like the MGTX,” the researchers wrote.
Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: A recently published prospective randomized trial provides definitive evidence that thymectomy significantly improves outcomes of patients with myasthenia gravis.
Major finding: Patients who underwent thymectomy had an average quantitative myasthenia score of 6.15 vs. 8.99 for the medical therapy group, a significant difference.
Data source: Myasthenia Gravis Thymectomy Trial, a prospective trial of 126 patients randomized to thymectomy with medical therapy or medical therapy alone.
Disclosures: Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
Pulmonary metastasectomy may be useful for soft-tissue sarcoma spread
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Characteristics that determine survival in patients with sarcomatous pulmonary metastases are tumor subtype and size, number of and time to metastases, and minimally invasive surgery.
Major finding: Patients with leiomyosarcoma histologic subtype tumor had a hazard ratio of 0.57 (P = .001), and those with a primary tumor size of 10 cm or less had an HR of 1, vs. an HR of 1.37 for those greater than 10 cm (P = .006)
Data source: A single-institution study of 539 patients who had pulmonary mastectomy for metastatic soft tissue sarcoma from September 1991 to June 2014.
Disclosures: Dr. Chudgar and his coauthors had no financial relationships to disclose.
Outcomes/costs similar for minimally invasive vs. sternotomy-based mitral surgery
NEW YORK – Minimally invasive mitral valve surgery provides outcomes that match those of conventional sternotomy without increasing use of resources, and lower costs after surgery offset potentially higher operation costs, according to a single-center, propensity-matched analysis of almost 500 patients presented at the meeting sponsored by the American Association for Thoracic Surgery.
“Minimally invasive mitral surgery has excellent outcomes with fewer transfusions and less time ventilated in this representative cohort,” said Robert Hawkins, MD, of the University of Virginia, Charlottesville, in reporting the results.
“While operative times were longer, surgical costs remained statistically similar, and minimally invasive mitral surgery was associated with similar total costs in more complex mitral cases.”
Dr. Hawkins said this study included higher risk patients to attempt to overcome shortcomings of previously published reports that skewed toward lower-risk, highly selective mitral repairs for degenerative mitral disease. “They’re not really representative of the current state of minimally invasive mitral valve surgery as it currently stands in the higher risk patient population,” he said of previous studies.
Major outcomes were similar in both groups. “The mitral valve repair rate was about 81% for both groups, and the tricuspid valve repair rate was 8.8%,” Dr. Hawkins said. “About 35% had atrial fibrillation surgery, including both ablation and left atrial appendage ligation.”
Dr. Hawkins characterized outcomes in both surgical groups as “excellent,” and added, “The operative mortality rate was 1.3% and the major morbidity rate was 11% and not different between groups.”
Some key operative characteristics differed between the two groups. “As expected the cross clamp times and bypass times for the minimally invasive approaches were longer,” Dr. Hawkins said. Also, those who had minimally invasive mitral surgery had a “dramatic decrease” in transfusion rates.
With regard to resource utilization, minimally invasive surgery had longer operative times – an average of 291 minutes vs. 222 minutes (P less than .0001) – but similar or improved use of postoperative resources. “We see that the minimally invasive approach leads to decreased treatment and ancillary costs without a statistically significant difference in surgical costs despite the longer operative times,” Dr. Hawkins said.
However, he noted the high variability of total hospital costs in higher-risk populations complicate any head-to-head comparisons of resource utilization between the conventional and minimally invasive approaches, so the researchers attempted to drill down to identify predictors of resource use. Using a regression model, they found that minimally invasive approach may actually save money, although this finding was not statistically significant (–$1,524; P = 0.83).
“We see that the major drivers of costs are complications,” Dr. Hawkins said. “Morbidity and mortality led to a $54,000 cost increase, and the addition of tricuspid repair also led to about $60,000 higher costs, which is more likely related to higher risk and thus complications. The costs of higher-acuity cases are driven by the complications and not the approach.”
Dr. Hawkins reported no financial relationships. Dr. Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
NEW YORK – Minimally invasive mitral valve surgery provides outcomes that match those of conventional sternotomy without increasing use of resources, and lower costs after surgery offset potentially higher operation costs, according to a single-center, propensity-matched analysis of almost 500 patients presented at the meeting sponsored by the American Association for Thoracic Surgery.
“Minimally invasive mitral surgery has excellent outcomes with fewer transfusions and less time ventilated in this representative cohort,” said Robert Hawkins, MD, of the University of Virginia, Charlottesville, in reporting the results.
“While operative times were longer, surgical costs remained statistically similar, and minimally invasive mitral surgery was associated with similar total costs in more complex mitral cases.”
Dr. Hawkins said this study included higher risk patients to attempt to overcome shortcomings of previously published reports that skewed toward lower-risk, highly selective mitral repairs for degenerative mitral disease. “They’re not really representative of the current state of minimally invasive mitral valve surgery as it currently stands in the higher risk patient population,” he said of previous studies.
Major outcomes were similar in both groups. “The mitral valve repair rate was about 81% for both groups, and the tricuspid valve repair rate was 8.8%,” Dr. Hawkins said. “About 35% had atrial fibrillation surgery, including both ablation and left atrial appendage ligation.”
Dr. Hawkins characterized outcomes in both surgical groups as “excellent,” and added, “The operative mortality rate was 1.3% and the major morbidity rate was 11% and not different between groups.”
Some key operative characteristics differed between the two groups. “As expected the cross clamp times and bypass times for the minimally invasive approaches were longer,” Dr. Hawkins said. Also, those who had minimally invasive mitral surgery had a “dramatic decrease” in transfusion rates.
With regard to resource utilization, minimally invasive surgery had longer operative times – an average of 291 minutes vs. 222 minutes (P less than .0001) – but similar or improved use of postoperative resources. “We see that the minimally invasive approach leads to decreased treatment and ancillary costs without a statistically significant difference in surgical costs despite the longer operative times,” Dr. Hawkins said.
However, he noted the high variability of total hospital costs in higher-risk populations complicate any head-to-head comparisons of resource utilization between the conventional and minimally invasive approaches, so the researchers attempted to drill down to identify predictors of resource use. Using a regression model, they found that minimally invasive approach may actually save money, although this finding was not statistically significant (–$1,524; P = 0.83).
“We see that the major drivers of costs are complications,” Dr. Hawkins said. “Morbidity and mortality led to a $54,000 cost increase, and the addition of tricuspid repair also led to about $60,000 higher costs, which is more likely related to higher risk and thus complications. The costs of higher-acuity cases are driven by the complications and not the approach.”
Dr. Hawkins reported no financial relationships. Dr. Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
NEW YORK – Minimally invasive mitral valve surgery provides outcomes that match those of conventional sternotomy without increasing use of resources, and lower costs after surgery offset potentially higher operation costs, according to a single-center, propensity-matched analysis of almost 500 patients presented at the meeting sponsored by the American Association for Thoracic Surgery.
“Minimally invasive mitral surgery has excellent outcomes with fewer transfusions and less time ventilated in this representative cohort,” said Robert Hawkins, MD, of the University of Virginia, Charlottesville, in reporting the results.
“While operative times were longer, surgical costs remained statistically similar, and minimally invasive mitral surgery was associated with similar total costs in more complex mitral cases.”
Dr. Hawkins said this study included higher risk patients to attempt to overcome shortcomings of previously published reports that skewed toward lower-risk, highly selective mitral repairs for degenerative mitral disease. “They’re not really representative of the current state of minimally invasive mitral valve surgery as it currently stands in the higher risk patient population,” he said of previous studies.
Major outcomes were similar in both groups. “The mitral valve repair rate was about 81% for both groups, and the tricuspid valve repair rate was 8.8%,” Dr. Hawkins said. “About 35% had atrial fibrillation surgery, including both ablation and left atrial appendage ligation.”
Dr. Hawkins characterized outcomes in both surgical groups as “excellent,” and added, “The operative mortality rate was 1.3% and the major morbidity rate was 11% and not different between groups.”
Some key operative characteristics differed between the two groups. “As expected the cross clamp times and bypass times for the minimally invasive approaches were longer,” Dr. Hawkins said. Also, those who had minimally invasive mitral surgery had a “dramatic decrease” in transfusion rates.
With regard to resource utilization, minimally invasive surgery had longer operative times – an average of 291 minutes vs. 222 minutes (P less than .0001) – but similar or improved use of postoperative resources. “We see that the minimally invasive approach leads to decreased treatment and ancillary costs without a statistically significant difference in surgical costs despite the longer operative times,” Dr. Hawkins said.
However, he noted the high variability of total hospital costs in higher-risk populations complicate any head-to-head comparisons of resource utilization between the conventional and minimally invasive approaches, so the researchers attempted to drill down to identify predictors of resource use. Using a regression model, they found that minimally invasive approach may actually save money, although this finding was not statistically significant (–$1,524; P = 0.83).
“We see that the major drivers of costs are complications,” Dr. Hawkins said. “Morbidity and mortality led to a $54,000 cost increase, and the addition of tricuspid repair also led to about $60,000 higher costs, which is more likely related to higher risk and thus complications. The costs of higher-acuity cases are driven by the complications and not the approach.”
Dr. Hawkins reported no financial relationships. Dr. Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
AT THE 2017 MITRAL VALVE CONCLAVE
Key clinical point: Outcomes and costs of minimally invasive mitral surgery are similar to that of conventional sternotomy for mitral valve surgery.
Major finding: Mortality rates of 1.3% and major morbidity rates of 11% were similar in both groups.
Data source: Propensity-matched analysis of 479 patients who had a primary mitral valve operation from January 2010 to June 2016 at the University of Virginia.
Disclosures: Dr. Hawkins reported no financial disclosures. Coauthor Dr. Gorav Ailawadi disclosed consulting agreements with Edwards Lifesciences, Abbott, Medtronic, and AtriCure.
Concomitant MIMV-TVS no worse than MIMV alone
NEW YORK – Concurrent mitral-tricuspid valve surgery has similar outcomes to isolated minimally invasive mitral valve surgery, according to results of a 12-year review reported at the 2017 Mitral Valve Conclave, sponsored by the American Association for Thoracic Surgery.
Indications for minimally invasive tricuspid valve surgery done at the same time of mitral valve surgery have not been well established, in part because the outcomes of such combined procedures have been underreported.
Dr. Kilic noted that patients who had concomitant TVS were typically higher risk at baseline. “The concomitant group was older, had a higher percentage of female patients, and higher rates of chronic lung disease and cerebrovascular disease as well,” Dr. Kilic said. In comparing the isolated MIMV surgery and MIMV-TVS groups in the unmatched analysis, 9% vs. 14% had chronic lung disease (P = .05), 12% vs. 16% had coronary artery disease (P = .15), 7% vs. 12% had cerebrovascular disease (P = .04), and 93% vs. 90% had elective surgery (P = .18). The majority of tricuspid repairs were for severe tricuspid regurgitation (TR) or moderate TR with a dilated annulus of 40 mm or greater.
The operative characteristics differed significantly between the two groups. “As one might expect, the cardiopulmonary bypass time and aortic occlusion times were longer in the concomitant group; and balloon aortic occlusion was used in more than 70% in each cohort,” Dr. Kilic said. Those differences were similar in the propensity-matched cohort: bypass times were 147.5 minutes for isolated MIMV surgery and 174.6 minutes for MIMV-TVS (P less than .001); and aortic occlusion time 104.8 vs. 128 minutes (P less than .001), respectively.
Operative mortality was 3% for isolated MIMV surgery and 4% for concurrent MIMV-TVS (P = .73), but the isolated MIMV surgery group required fewer permanent pacemakers, 1% vs. 6% (P = .03).
“Aside from permanent pacemaker implantation, the rates of every other complication were similar, including stoke, limb ischemia, atrial fibrillation, gastrointestinal complications, respiratory complications, blood product transfusions as well as discharge to home rates,” Dr. Kilic said. Median hospital length of stays were also similar: 7 days for isolated MIMV surgery vs. 8 days for MIMV-TVS (P = .13).
One limitation of the study Dr. Kilic pointed out was that the decision to perform concomitant MIMV-TVS was surgeon dependent.
Dr. Kilic reported having no financial disclosures.
NEW YORK – Concurrent mitral-tricuspid valve surgery has similar outcomes to isolated minimally invasive mitral valve surgery, according to results of a 12-year review reported at the 2017 Mitral Valve Conclave, sponsored by the American Association for Thoracic Surgery.
Indications for minimally invasive tricuspid valve surgery done at the same time of mitral valve surgery have not been well established, in part because the outcomes of such combined procedures have been underreported.
Dr. Kilic noted that patients who had concomitant TVS were typically higher risk at baseline. “The concomitant group was older, had a higher percentage of female patients, and higher rates of chronic lung disease and cerebrovascular disease as well,” Dr. Kilic said. In comparing the isolated MIMV surgery and MIMV-TVS groups in the unmatched analysis, 9% vs. 14% had chronic lung disease (P = .05), 12% vs. 16% had coronary artery disease (P = .15), 7% vs. 12% had cerebrovascular disease (P = .04), and 93% vs. 90% had elective surgery (P = .18). The majority of tricuspid repairs were for severe tricuspid regurgitation (TR) or moderate TR with a dilated annulus of 40 mm or greater.
The operative characteristics differed significantly between the two groups. “As one might expect, the cardiopulmonary bypass time and aortic occlusion times were longer in the concomitant group; and balloon aortic occlusion was used in more than 70% in each cohort,” Dr. Kilic said. Those differences were similar in the propensity-matched cohort: bypass times were 147.5 minutes for isolated MIMV surgery and 174.6 minutes for MIMV-TVS (P less than .001); and aortic occlusion time 104.8 vs. 128 minutes (P less than .001), respectively.
Operative mortality was 3% for isolated MIMV surgery and 4% for concurrent MIMV-TVS (P = .73), but the isolated MIMV surgery group required fewer permanent pacemakers, 1% vs. 6% (P = .03).
“Aside from permanent pacemaker implantation, the rates of every other complication were similar, including stoke, limb ischemia, atrial fibrillation, gastrointestinal complications, respiratory complications, blood product transfusions as well as discharge to home rates,” Dr. Kilic said. Median hospital length of stays were also similar: 7 days for isolated MIMV surgery vs. 8 days for MIMV-TVS (P = .13).
One limitation of the study Dr. Kilic pointed out was that the decision to perform concomitant MIMV-TVS was surgeon dependent.
Dr. Kilic reported having no financial disclosures.
NEW YORK – Concurrent mitral-tricuspid valve surgery has similar outcomes to isolated minimally invasive mitral valve surgery, according to results of a 12-year review reported at the 2017 Mitral Valve Conclave, sponsored by the American Association for Thoracic Surgery.
Indications for minimally invasive tricuspid valve surgery done at the same time of mitral valve surgery have not been well established, in part because the outcomes of such combined procedures have been underreported.
Dr. Kilic noted that patients who had concomitant TVS were typically higher risk at baseline. “The concomitant group was older, had a higher percentage of female patients, and higher rates of chronic lung disease and cerebrovascular disease as well,” Dr. Kilic said. In comparing the isolated MIMV surgery and MIMV-TVS groups in the unmatched analysis, 9% vs. 14% had chronic lung disease (P = .05), 12% vs. 16% had coronary artery disease (P = .15), 7% vs. 12% had cerebrovascular disease (P = .04), and 93% vs. 90% had elective surgery (P = .18). The majority of tricuspid repairs were for severe tricuspid regurgitation (TR) or moderate TR with a dilated annulus of 40 mm or greater.
The operative characteristics differed significantly between the two groups. “As one might expect, the cardiopulmonary bypass time and aortic occlusion times were longer in the concomitant group; and balloon aortic occlusion was used in more than 70% in each cohort,” Dr. Kilic said. Those differences were similar in the propensity-matched cohort: bypass times were 147.5 minutes for isolated MIMV surgery and 174.6 minutes for MIMV-TVS (P less than .001); and aortic occlusion time 104.8 vs. 128 minutes (P less than .001), respectively.
Operative mortality was 3% for isolated MIMV surgery and 4% for concurrent MIMV-TVS (P = .73), but the isolated MIMV surgery group required fewer permanent pacemakers, 1% vs. 6% (P = .03).
“Aside from permanent pacemaker implantation, the rates of every other complication were similar, including stoke, limb ischemia, atrial fibrillation, gastrointestinal complications, respiratory complications, blood product transfusions as well as discharge to home rates,” Dr. Kilic said. Median hospital length of stays were also similar: 7 days for isolated MIMV surgery vs. 8 days for MIMV-TVS (P = .13).
One limitation of the study Dr. Kilic pointed out was that the decision to perform concomitant MIMV-TVS was surgeon dependent.
Dr. Kilic reported having no financial disclosures.
AT THE 2017 MITRAL VALVE CONCLAVE
Key clinical point: Outcomes of isolated minimally invasive mitral valve surgery (MIMV) and MIMV with concomitant tricuspid valve surgery (TVS) are similar.
Major finding: Operative mortality was 3% for isolated MIMV and 4% for concurrent MIMV-TVS.
Data source: Single-center review of 1,158 patients who underwent either isolated MIMV or MIMV-TVS from 2002 to 2014, including a propensity-matched cohort.
Disclosures: Dr. Kilic reported having no financial disclosures.