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Early, in-hospital shunt failure common among infants
HOUSTON – Among neonates and infants who underwent shunt construction as a source of pulmonary blood flow, early, in-hospital shunt failure occurred in 7.3% of cases, results from a large retrospective study showed.
“Approximately one in seven patients who experiences cardiac surgery in the first year of life undergoes construction of a systemic to pulmonary artery shunt of some type,” one of the study investigators, Marshall L. Jacobs, MD, said in an interview. The study was presented at the annual meeting of the Society of Thoracic Surgeons.
“Early failure of such shunts is an incompletely understood phenomenon which accounts for important morbidity and mortality among infants and neonates. Much of what is known about shunt failure is based on experiences reported from individual institutions. The few multicenter studies to date have been clinical trials that focused primarily on pharmacologic strategies intended to reduce the risk of shunt failure due to thrombosis. Their utility for guiding clinical decision making has been limited. Some have been underpowered; some have had limited risk adjustment of subjects.”
Dr. Do, who presented the findings at the meeting and is currently a Congenital Heart Surgery Fellow at the Children’s Hospital of Philadelphia, and a team of 11 other investigators utilized the STS Congenital Heart Surgery Database to identify 9,172 neonates and infants who underwent shunt construction as a source of pulmonary blood flow at 118 institutions from 2010 to 2015. Criteria for shunt failure included a documented diagnosis of in-hospital shunt failure, shunt revision, or catheter-based shunt intervention. The investigators used multivariable logistic regression to evaluate risk factors for in-hospital shunt failure.
Of the 9,172 at-risk neonates and infants, 674 (7.3%) experienced early, in-hospital shunt failure. “The observed rate of early shunt failure varied across the many specific types of shunts, and was lower with systemic ventricle to pulmonary artery shunts (as in the Sano modification of the Norwood procedure) than with the systemic artery to pulmonary artery shunts,” said Dr. Jacobs, who is a cardiothoracic surgeon at Johns Hopkins University, Baltimore.
In multivariable analysis, risk factors for in-hospital shunt failure included lower weight at operation for both neonates and infants, preoperative hypercoagulable state, and the collective presence of any other STS Congenital Heart Surgery Database preoperative risk factors. Neither cardiopulmonary bypass nor single ventricle diagnosis were risk factors for shunt failure. The investigators also observed that patients with in-hospital shunt failure had significantly higher rates of operative mortality (31.9% vs. 11.1%) and major morbidity (84.4% vs. 29.4%), and longer postoperative length of stay among survivors (a median of 45 vs. 22 days).
“Understanding the characteristics of the patient groups found to be at highest risk for early shunt failure is helpful in identifying individual patients that may warrant expectant surveillance, enhanced pharmacologic management, or other strategies to reduce the risk of shunt failure,” Dr. Jacobs concluded.
“But perhaps more importantly it provides key information that may be helpful in the design and development of future clinical trials and/or collaborative quality improvement initiatives designed to reduce the cost in lives and resources that is associated with early shunt dysfunction.”
He acknowledged certain limitations of the study, including its retrospective observational design and the voluntary nature of the STS Congenital Heart Surgery Database. “In addition, some potentially important variables, such as detailed data concerning preoperative test results of coagulation assays are not collected in the STS Congenital Heart Surgery Database,” he said.
The research was supported by the STS Access & Publications Research program. The investigators reported having no financial disclosures.
HOUSTON – Among neonates and infants who underwent shunt construction as a source of pulmonary blood flow, early, in-hospital shunt failure occurred in 7.3% of cases, results from a large retrospective study showed.
“Approximately one in seven patients who experiences cardiac surgery in the first year of life undergoes construction of a systemic to pulmonary artery shunt of some type,” one of the study investigators, Marshall L. Jacobs, MD, said in an interview. The study was presented at the annual meeting of the Society of Thoracic Surgeons.
“Early failure of such shunts is an incompletely understood phenomenon which accounts for important morbidity and mortality among infants and neonates. Much of what is known about shunt failure is based on experiences reported from individual institutions. The few multicenter studies to date have been clinical trials that focused primarily on pharmacologic strategies intended to reduce the risk of shunt failure due to thrombosis. Their utility for guiding clinical decision making has been limited. Some have been underpowered; some have had limited risk adjustment of subjects.”
Dr. Do, who presented the findings at the meeting and is currently a Congenital Heart Surgery Fellow at the Children’s Hospital of Philadelphia, and a team of 11 other investigators utilized the STS Congenital Heart Surgery Database to identify 9,172 neonates and infants who underwent shunt construction as a source of pulmonary blood flow at 118 institutions from 2010 to 2015. Criteria for shunt failure included a documented diagnosis of in-hospital shunt failure, shunt revision, or catheter-based shunt intervention. The investigators used multivariable logistic regression to evaluate risk factors for in-hospital shunt failure.
Of the 9,172 at-risk neonates and infants, 674 (7.3%) experienced early, in-hospital shunt failure. “The observed rate of early shunt failure varied across the many specific types of shunts, and was lower with systemic ventricle to pulmonary artery shunts (as in the Sano modification of the Norwood procedure) than with the systemic artery to pulmonary artery shunts,” said Dr. Jacobs, who is a cardiothoracic surgeon at Johns Hopkins University, Baltimore.
In multivariable analysis, risk factors for in-hospital shunt failure included lower weight at operation for both neonates and infants, preoperative hypercoagulable state, and the collective presence of any other STS Congenital Heart Surgery Database preoperative risk factors. Neither cardiopulmonary bypass nor single ventricle diagnosis were risk factors for shunt failure. The investigators also observed that patients with in-hospital shunt failure had significantly higher rates of operative mortality (31.9% vs. 11.1%) and major morbidity (84.4% vs. 29.4%), and longer postoperative length of stay among survivors (a median of 45 vs. 22 days).
“Understanding the characteristics of the patient groups found to be at highest risk for early shunt failure is helpful in identifying individual patients that may warrant expectant surveillance, enhanced pharmacologic management, or other strategies to reduce the risk of shunt failure,” Dr. Jacobs concluded.
“But perhaps more importantly it provides key information that may be helpful in the design and development of future clinical trials and/or collaborative quality improvement initiatives designed to reduce the cost in lives and resources that is associated with early shunt dysfunction.”
He acknowledged certain limitations of the study, including its retrospective observational design and the voluntary nature of the STS Congenital Heart Surgery Database. “In addition, some potentially important variables, such as detailed data concerning preoperative test results of coagulation assays are not collected in the STS Congenital Heart Surgery Database,” he said.
The research was supported by the STS Access & Publications Research program. The investigators reported having no financial disclosures.
HOUSTON – Among neonates and infants who underwent shunt construction as a source of pulmonary blood flow, early, in-hospital shunt failure occurred in 7.3% of cases, results from a large retrospective study showed.
“Approximately one in seven patients who experiences cardiac surgery in the first year of life undergoes construction of a systemic to pulmonary artery shunt of some type,” one of the study investigators, Marshall L. Jacobs, MD, said in an interview. The study was presented at the annual meeting of the Society of Thoracic Surgeons.
“Early failure of such shunts is an incompletely understood phenomenon which accounts for important morbidity and mortality among infants and neonates. Much of what is known about shunt failure is based on experiences reported from individual institutions. The few multicenter studies to date have been clinical trials that focused primarily on pharmacologic strategies intended to reduce the risk of shunt failure due to thrombosis. Their utility for guiding clinical decision making has been limited. Some have been underpowered; some have had limited risk adjustment of subjects.”
Dr. Do, who presented the findings at the meeting and is currently a Congenital Heart Surgery Fellow at the Children’s Hospital of Philadelphia, and a team of 11 other investigators utilized the STS Congenital Heart Surgery Database to identify 9,172 neonates and infants who underwent shunt construction as a source of pulmonary blood flow at 118 institutions from 2010 to 2015. Criteria for shunt failure included a documented diagnosis of in-hospital shunt failure, shunt revision, or catheter-based shunt intervention. The investigators used multivariable logistic regression to evaluate risk factors for in-hospital shunt failure.
Of the 9,172 at-risk neonates and infants, 674 (7.3%) experienced early, in-hospital shunt failure. “The observed rate of early shunt failure varied across the many specific types of shunts, and was lower with systemic ventricle to pulmonary artery shunts (as in the Sano modification of the Norwood procedure) than with the systemic artery to pulmonary artery shunts,” said Dr. Jacobs, who is a cardiothoracic surgeon at Johns Hopkins University, Baltimore.
In multivariable analysis, risk factors for in-hospital shunt failure included lower weight at operation for both neonates and infants, preoperative hypercoagulable state, and the collective presence of any other STS Congenital Heart Surgery Database preoperative risk factors. Neither cardiopulmonary bypass nor single ventricle diagnosis were risk factors for shunt failure. The investigators also observed that patients with in-hospital shunt failure had significantly higher rates of operative mortality (31.9% vs. 11.1%) and major morbidity (84.4% vs. 29.4%), and longer postoperative length of stay among survivors (a median of 45 vs. 22 days).
“Understanding the characteristics of the patient groups found to be at highest risk for early shunt failure is helpful in identifying individual patients that may warrant expectant surveillance, enhanced pharmacologic management, or other strategies to reduce the risk of shunt failure,” Dr. Jacobs concluded.
“But perhaps more importantly it provides key information that may be helpful in the design and development of future clinical trials and/or collaborative quality improvement initiatives designed to reduce the cost in lives and resources that is associated with early shunt dysfunction.”
He acknowledged certain limitations of the study, including its retrospective observational design and the voluntary nature of the STS Congenital Heart Surgery Database. “In addition, some potentially important variables, such as detailed data concerning preoperative test results of coagulation assays are not collected in the STS Congenital Heart Surgery Database,” he said.
The research was supported by the STS Access & Publications Research program. The investigators reported having no financial disclosures.
AT THE STS ANNUAL MEETING
Key clinical point:
Major finding: Among neonates and infants who underwent shunt operations, 7.3% experienced early, in-hospital shunt failure.
Data source: A retrospective analysis of 9,172 neonates and infants who underwent shunt construction as a source of pulmonary blood flow at 118 institutions from 2010 to 2015.
Disclosures: The research was supported by the STS Access & Publications Research program. The investigators reported having no financial disclosures.
Study IDs risk factors for ideal timing of stage 2 palliation following Norwood
HOUSTON – The optimal timing of stage 2 palliation after the Norwood operation depends on certain patient-specific risk factors, but in most cases should be done around 3-4 months of age, results from a multi-center study show.
While previous studies have investigated whether early stage-2 palliation (S2P) can be performed without increased post-S2P mortality, the effect of the timing of S2P on post-Norwood mortality remains unknown, Robert “Jake” Jaquiss, MD, said in an interview in advance of the annual meeting of the Society of Thoracic Surgeons.
“There has been a lot of dispute about how early is too early for S2P,” said Dr. Jaquiss, the study’s senior author, who is professor and division chief of pediatric cardiothoracic surgery at the University of Texas Southwestern Medical Center. “That is one of the few things that is in the control of the doctor. Most of the rest of the decisions are based entirely on the condition of the patient and the patient’s specific anatomy. So the timing of S2P is something that we can truly define most always. What we want to find out is, what is the ideal timing? How early is too early? Is there such a thing as too late?”
In an effort to determine the optimal timing of S2P that both minimizes pre-S2P attrition and maximizes long-term post-S2P survival, Dr. Jaquiss and his associates at 19 other institutions evaluated data from 534 neonates diagnosed with left ventricular outflow tract obstruction that precluded adequate systemic cardiac output through the aortic valve who initially underwent a Norwood operation from 2005 to 2016.
S2P was performed in 377 patients (71%) at a mean age of 5.4 months, while 115 (22%) died after Norwood, and the rest underwent biventricular repair or heart transplantation. After S2P, 38 (10%) died, 248 (66%) underwent Fontan, and the rest were alive awaiting Fontan or underwent heart transplantation.
Risk factors for death after Norwood included requiring pre-Norwood extracorporeal membrane oxygenation (P less than .0001), birth weight of less than 2.5 kg (P less than .0001), modified Blalock-Taussig shunt vs. a right ventricle to pulmonary artery conduit (P = .0003), larger baseline right pulmonary artery diameter (P = .0002), smaller baseline mitral valve diameter (P = .0002), smaller baseline tricuspid valve diameter (P = .0001), and nonwhite race (P = .03).
Risk factors for death after S2P included lower oxygen saturation at pre-S2P clinic visit (P = .02), having moderate or severe pre-S2P right ventricular dysfunction (P = .007), younger age at S2P (P = .03), and longer post-Norwood hospital length of stay (P = .03).
The risk-adjusted, 4-year, post-Norwood survival was 72%, with a confidence interval of 67%-75%. When plotted vs. the age at S2P, risk-adjusted, 4-year, post-Norwood survival for the 534 patients was maximized by S2P at 3-6 months of age. At the same time, risk-adjusted, 4-year survival in low-risk infants was compromised only by undergoing S2P earlier than 3 months of age. In high-risk infants, survival was severely compromised, especially when undergoing S2P earlier than 6 months of age.
“The results reinforced intuitions or expectations that most of the investigators already had,” Dr. Jaquiss said. “But we are in an era where evidence-based medicine is much preferable to intuition-based medicine. I’m very confident in the findings we have. I feel more confident in suggesting that we should be planning these surgeries around 3-4 months of age in usual-risk children and also more confident in suggesting that we need to consider transplantation earlier in children who are perceived to be at high risk. There is some hope [by clinicians in] some centers that you can convert a high-risk prognosis to a lower or intermediate risk prognosis by doing the S2P earlier or at some alternative time. Our data suggests that would not be helpful.”
Dr. Jaquiss and Dr. Meza reported having no financial disclosures.
HOUSTON – The optimal timing of stage 2 palliation after the Norwood operation depends on certain patient-specific risk factors, but in most cases should be done around 3-4 months of age, results from a multi-center study show.
While previous studies have investigated whether early stage-2 palliation (S2P) can be performed without increased post-S2P mortality, the effect of the timing of S2P on post-Norwood mortality remains unknown, Robert “Jake” Jaquiss, MD, said in an interview in advance of the annual meeting of the Society of Thoracic Surgeons.
“There has been a lot of dispute about how early is too early for S2P,” said Dr. Jaquiss, the study’s senior author, who is professor and division chief of pediatric cardiothoracic surgery at the University of Texas Southwestern Medical Center. “That is one of the few things that is in the control of the doctor. Most of the rest of the decisions are based entirely on the condition of the patient and the patient’s specific anatomy. So the timing of S2P is something that we can truly define most always. What we want to find out is, what is the ideal timing? How early is too early? Is there such a thing as too late?”
In an effort to determine the optimal timing of S2P that both minimizes pre-S2P attrition and maximizes long-term post-S2P survival, Dr. Jaquiss and his associates at 19 other institutions evaluated data from 534 neonates diagnosed with left ventricular outflow tract obstruction that precluded adequate systemic cardiac output through the aortic valve who initially underwent a Norwood operation from 2005 to 2016.
S2P was performed in 377 patients (71%) at a mean age of 5.4 months, while 115 (22%) died after Norwood, and the rest underwent biventricular repair or heart transplantation. After S2P, 38 (10%) died, 248 (66%) underwent Fontan, and the rest were alive awaiting Fontan or underwent heart transplantation.
Risk factors for death after Norwood included requiring pre-Norwood extracorporeal membrane oxygenation (P less than .0001), birth weight of less than 2.5 kg (P less than .0001), modified Blalock-Taussig shunt vs. a right ventricle to pulmonary artery conduit (P = .0003), larger baseline right pulmonary artery diameter (P = .0002), smaller baseline mitral valve diameter (P = .0002), smaller baseline tricuspid valve diameter (P = .0001), and nonwhite race (P = .03).
Risk factors for death after S2P included lower oxygen saturation at pre-S2P clinic visit (P = .02), having moderate or severe pre-S2P right ventricular dysfunction (P = .007), younger age at S2P (P = .03), and longer post-Norwood hospital length of stay (P = .03).
The risk-adjusted, 4-year, post-Norwood survival was 72%, with a confidence interval of 67%-75%. When plotted vs. the age at S2P, risk-adjusted, 4-year, post-Norwood survival for the 534 patients was maximized by S2P at 3-6 months of age. At the same time, risk-adjusted, 4-year survival in low-risk infants was compromised only by undergoing S2P earlier than 3 months of age. In high-risk infants, survival was severely compromised, especially when undergoing S2P earlier than 6 months of age.
“The results reinforced intuitions or expectations that most of the investigators already had,” Dr. Jaquiss said. “But we are in an era where evidence-based medicine is much preferable to intuition-based medicine. I’m very confident in the findings we have. I feel more confident in suggesting that we should be planning these surgeries around 3-4 months of age in usual-risk children and also more confident in suggesting that we need to consider transplantation earlier in children who are perceived to be at high risk. There is some hope [by clinicians in] some centers that you can convert a high-risk prognosis to a lower or intermediate risk prognosis by doing the S2P earlier or at some alternative time. Our data suggests that would not be helpful.”
Dr. Jaquiss and Dr. Meza reported having no financial disclosures.
HOUSTON – The optimal timing of stage 2 palliation after the Norwood operation depends on certain patient-specific risk factors, but in most cases should be done around 3-4 months of age, results from a multi-center study show.
While previous studies have investigated whether early stage-2 palliation (S2P) can be performed without increased post-S2P mortality, the effect of the timing of S2P on post-Norwood mortality remains unknown, Robert “Jake” Jaquiss, MD, said in an interview in advance of the annual meeting of the Society of Thoracic Surgeons.
“There has been a lot of dispute about how early is too early for S2P,” said Dr. Jaquiss, the study’s senior author, who is professor and division chief of pediatric cardiothoracic surgery at the University of Texas Southwestern Medical Center. “That is one of the few things that is in the control of the doctor. Most of the rest of the decisions are based entirely on the condition of the patient and the patient’s specific anatomy. So the timing of S2P is something that we can truly define most always. What we want to find out is, what is the ideal timing? How early is too early? Is there such a thing as too late?”
In an effort to determine the optimal timing of S2P that both minimizes pre-S2P attrition and maximizes long-term post-S2P survival, Dr. Jaquiss and his associates at 19 other institutions evaluated data from 534 neonates diagnosed with left ventricular outflow tract obstruction that precluded adequate systemic cardiac output through the aortic valve who initially underwent a Norwood operation from 2005 to 2016.
S2P was performed in 377 patients (71%) at a mean age of 5.4 months, while 115 (22%) died after Norwood, and the rest underwent biventricular repair or heart transplantation. After S2P, 38 (10%) died, 248 (66%) underwent Fontan, and the rest were alive awaiting Fontan or underwent heart transplantation.
Risk factors for death after Norwood included requiring pre-Norwood extracorporeal membrane oxygenation (P less than .0001), birth weight of less than 2.5 kg (P less than .0001), modified Blalock-Taussig shunt vs. a right ventricle to pulmonary artery conduit (P = .0003), larger baseline right pulmonary artery diameter (P = .0002), smaller baseline mitral valve diameter (P = .0002), smaller baseline tricuspid valve diameter (P = .0001), and nonwhite race (P = .03).
Risk factors for death after S2P included lower oxygen saturation at pre-S2P clinic visit (P = .02), having moderate or severe pre-S2P right ventricular dysfunction (P = .007), younger age at S2P (P = .03), and longer post-Norwood hospital length of stay (P = .03).
The risk-adjusted, 4-year, post-Norwood survival was 72%, with a confidence interval of 67%-75%. When plotted vs. the age at S2P, risk-adjusted, 4-year, post-Norwood survival for the 534 patients was maximized by S2P at 3-6 months of age. At the same time, risk-adjusted, 4-year survival in low-risk infants was compromised only by undergoing S2P earlier than 3 months of age. In high-risk infants, survival was severely compromised, especially when undergoing S2P earlier than 6 months of age.
“The results reinforced intuitions or expectations that most of the investigators already had,” Dr. Jaquiss said. “But we are in an era where evidence-based medicine is much preferable to intuition-based medicine. I’m very confident in the findings we have. I feel more confident in suggesting that we should be planning these surgeries around 3-4 months of age in usual-risk children and also more confident in suggesting that we need to consider transplantation earlier in children who are perceived to be at high risk. There is some hope [by clinicians in] some centers that you can convert a high-risk prognosis to a lower or intermediate risk prognosis by doing the S2P earlier or at some alternative time. Our data suggests that would not be helpful.”
Dr. Jaquiss and Dr. Meza reported having no financial disclosures.
Key clinical point:
Major finding: When plotted vs. the age at stage 2 palliation, risk-adjusted, 4-year, post-Norwood survival for the 534 patients was maximized by S2P at 3-6 months of age.
Data source: A multi-institutional analysis of 534 neonates diagnosed with left ventricular outflow tract obstruction that precluded adequate systemic cardiac output through the aortic valve who initially underwent a Norwood operation from 2005 to 2016.
Disclosures: Dr. Jaquiss and Dr. Meza reported having no financial disclosures.
Sleeve lobectomy appears better than pneumonectomy for NSCLC
Guidelines that recommend sleeve lobectomy as a means of avoiding pneumonectomy for lung cancer have been based on a limited retrospective series, but a large series drawn from a nationwide database in France has confirmed the preference for sleeve lobectomy because it leads to higher rates of survival, despite an increased risk of postoperative pulmonary complications.
“Whenever it is technically possible, surgeons must perform sleeve lobectomy to provide more long-term survival benefits to patients, even with the risk of more postoperative pulmonary complications,” said Pierre-Benoit Pagès, MD, PhD, and his coauthors in the January 2017 issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:184-95). Dr. Pagès is with the department of thoracic and cardiovascular surgery at the University Hospital Center Dijon (France) and Bocage Hospital.
Three-year overall survival was 71.9% for the sleeve lobectomy group vs. 60.8% for the pneumonectomy group. Three-year disease-free survival was 46.4% for the sleeve lobectomy group and 31.6% for the pneumonectomy group. In addition, compared with the sleeve lobectomy group, the pneumonectomy group had an increased risk of recurrence by matching (hazard ratio, 1.49; 95% CI, 1.1-2).
The researchers performed a propensity-matched analysis that favored sleeve lobectomy for early overall and disease-free survival, but the weighted analysis did not. Patients in the sleeve lobectomy group vs. the pneumonectomy group were younger (60.9 years vs. 61.9), had higher body mass index (25.6 vs. 25.1), had higher average forced expiratory volume (74.1% vs. 62.9%), and had lower American Society of Anesthesiologists scores (73.7% with scores of 1 and 2 vs. 70.8%). Sleeve lobectomy patients also were more likely to have right-sided surgery (69.6% vs. 41%) and squamous cell carcinoma (54.6% vs. 48.3%), and lower T and N stages (T1 and T2, 60.5% vs. 40.6%; N0, 40.9% vs. 26.2%).
Overall mortality after surgery was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group, but propensity scoring showed far fewer postoperative pulmonary complications in the pneumonectomy group, with an odds ratio of 0.4, Dr. Pagès and his coauthors said. However, with other significant complications – arrhythmia, bronchopleural fistula, empyema, and hemorrhage – pneumonectomy had a propensity-matched odds ratio ranging from 1.6 to 7. “We found no significant difference regarding postoperative mortality in the sleeve lobectomy and pneumonectomy groups, whatever the statistical method used,” Dr. Pagès and his coauthors wrote.
The investigators had no financial relationships to disclose.
The study by Dr. Pagès and his colleagues is unique in the field of surgery for non–small cell lung cancer in that it drew on a nationwide database using data from 103 centers, Betty C. Tong, MD, MHS, of Duke University Medical Center, Durham, said in her invited commentary (J Thorac Cardiovasc Surg. 2017;153:196). “These results are likely as close to real life as possible,” she said.
She acknowledged that no prospective, randomized controlled trials have compared sleeve lobectomy to pneumonectomy, but she added, “it is unlikely that such a trial could be successfully executed.” The 5:1 ratio of patients having pneumonectomy vs. sleeve lobectomy in this study is similar to findings from the Society of Thoracic Surgeons General Thoracic Surgery database (J Thorac Cardiovasc Surg. 2008;132:247-54), Dr. Tong pointed out, “and likely reflects the fact that sleeve lobectomy can be technically more difficult to perform.”
The findings of the French Society of Thoracic and Cardiovascular Surgery group “should strongly encourage thoracic surgeons to perform pneumonectomy as sparingly as possible,” and consider sleeve lobectomy the standard for patients with central tumors, Dr. Tong said.
She had no financial relationships to disclose.
The study by Dr. Pagès and his colleagues is unique in the field of surgery for non–small cell lung cancer in that it drew on a nationwide database using data from 103 centers, Betty C. Tong, MD, MHS, of Duke University Medical Center, Durham, said in her invited commentary (J Thorac Cardiovasc Surg. 2017;153:196). “These results are likely as close to real life as possible,” she said.
She acknowledged that no prospective, randomized controlled trials have compared sleeve lobectomy to pneumonectomy, but she added, “it is unlikely that such a trial could be successfully executed.” The 5:1 ratio of patients having pneumonectomy vs. sleeve lobectomy in this study is similar to findings from the Society of Thoracic Surgeons General Thoracic Surgery database (J Thorac Cardiovasc Surg. 2008;132:247-54), Dr. Tong pointed out, “and likely reflects the fact that sleeve lobectomy can be technically more difficult to perform.”
The findings of the French Society of Thoracic and Cardiovascular Surgery group “should strongly encourage thoracic surgeons to perform pneumonectomy as sparingly as possible,” and consider sleeve lobectomy the standard for patients with central tumors, Dr. Tong said.
She had no financial relationships to disclose.
The study by Dr. Pagès and his colleagues is unique in the field of surgery for non–small cell lung cancer in that it drew on a nationwide database using data from 103 centers, Betty C. Tong, MD, MHS, of Duke University Medical Center, Durham, said in her invited commentary (J Thorac Cardiovasc Surg. 2017;153:196). “These results are likely as close to real life as possible,” she said.
She acknowledged that no prospective, randomized controlled trials have compared sleeve lobectomy to pneumonectomy, but she added, “it is unlikely that such a trial could be successfully executed.” The 5:1 ratio of patients having pneumonectomy vs. sleeve lobectomy in this study is similar to findings from the Society of Thoracic Surgeons General Thoracic Surgery database (J Thorac Cardiovasc Surg. 2008;132:247-54), Dr. Tong pointed out, “and likely reflects the fact that sleeve lobectomy can be technically more difficult to perform.”
The findings of the French Society of Thoracic and Cardiovascular Surgery group “should strongly encourage thoracic surgeons to perform pneumonectomy as sparingly as possible,” and consider sleeve lobectomy the standard for patients with central tumors, Dr. Tong said.
She had no financial relationships to disclose.
Guidelines that recommend sleeve lobectomy as a means of avoiding pneumonectomy for lung cancer have been based on a limited retrospective series, but a large series drawn from a nationwide database in France has confirmed the preference for sleeve lobectomy because it leads to higher rates of survival, despite an increased risk of postoperative pulmonary complications.
“Whenever it is technically possible, surgeons must perform sleeve lobectomy to provide more long-term survival benefits to patients, even with the risk of more postoperative pulmonary complications,” said Pierre-Benoit Pagès, MD, PhD, and his coauthors in the January 2017 issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:184-95). Dr. Pagès is with the department of thoracic and cardiovascular surgery at the University Hospital Center Dijon (France) and Bocage Hospital.
Three-year overall survival was 71.9% for the sleeve lobectomy group vs. 60.8% for the pneumonectomy group. Three-year disease-free survival was 46.4% for the sleeve lobectomy group and 31.6% for the pneumonectomy group. In addition, compared with the sleeve lobectomy group, the pneumonectomy group had an increased risk of recurrence by matching (hazard ratio, 1.49; 95% CI, 1.1-2).
The researchers performed a propensity-matched analysis that favored sleeve lobectomy for early overall and disease-free survival, but the weighted analysis did not. Patients in the sleeve lobectomy group vs. the pneumonectomy group were younger (60.9 years vs. 61.9), had higher body mass index (25.6 vs. 25.1), had higher average forced expiratory volume (74.1% vs. 62.9%), and had lower American Society of Anesthesiologists scores (73.7% with scores of 1 and 2 vs. 70.8%). Sleeve lobectomy patients also were more likely to have right-sided surgery (69.6% vs. 41%) and squamous cell carcinoma (54.6% vs. 48.3%), and lower T and N stages (T1 and T2, 60.5% vs. 40.6%; N0, 40.9% vs. 26.2%).
Overall mortality after surgery was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group, but propensity scoring showed far fewer postoperative pulmonary complications in the pneumonectomy group, with an odds ratio of 0.4, Dr. Pagès and his coauthors said. However, with other significant complications – arrhythmia, bronchopleural fistula, empyema, and hemorrhage – pneumonectomy had a propensity-matched odds ratio ranging from 1.6 to 7. “We found no significant difference regarding postoperative mortality in the sleeve lobectomy and pneumonectomy groups, whatever the statistical method used,” Dr. Pagès and his coauthors wrote.
The investigators had no financial relationships to disclose.
Guidelines that recommend sleeve lobectomy as a means of avoiding pneumonectomy for lung cancer have been based on a limited retrospective series, but a large series drawn from a nationwide database in France has confirmed the preference for sleeve lobectomy because it leads to higher rates of survival, despite an increased risk of postoperative pulmonary complications.
“Whenever it is technically possible, surgeons must perform sleeve lobectomy to provide more long-term survival benefits to patients, even with the risk of more postoperative pulmonary complications,” said Pierre-Benoit Pagès, MD, PhD, and his coauthors in the January 2017 issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:184-95). Dr. Pagès is with the department of thoracic and cardiovascular surgery at the University Hospital Center Dijon (France) and Bocage Hospital.
Three-year overall survival was 71.9% for the sleeve lobectomy group vs. 60.8% for the pneumonectomy group. Three-year disease-free survival was 46.4% for the sleeve lobectomy group and 31.6% for the pneumonectomy group. In addition, compared with the sleeve lobectomy group, the pneumonectomy group had an increased risk of recurrence by matching (hazard ratio, 1.49; 95% CI, 1.1-2).
The researchers performed a propensity-matched analysis that favored sleeve lobectomy for early overall and disease-free survival, but the weighted analysis did not. Patients in the sleeve lobectomy group vs. the pneumonectomy group were younger (60.9 years vs. 61.9), had higher body mass index (25.6 vs. 25.1), had higher average forced expiratory volume (74.1% vs. 62.9%), and had lower American Society of Anesthesiologists scores (73.7% with scores of 1 and 2 vs. 70.8%). Sleeve lobectomy patients also were more likely to have right-sided surgery (69.6% vs. 41%) and squamous cell carcinoma (54.6% vs. 48.3%), and lower T and N stages (T1 and T2, 60.5% vs. 40.6%; N0, 40.9% vs. 26.2%).
Overall mortality after surgery was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group, but propensity scoring showed far fewer postoperative pulmonary complications in the pneumonectomy group, with an odds ratio of 0.4, Dr. Pagès and his coauthors said. However, with other significant complications – arrhythmia, bronchopleural fistula, empyema, and hemorrhage – pneumonectomy had a propensity-matched odds ratio ranging from 1.6 to 7. “We found no significant difference regarding postoperative mortality in the sleeve lobectomy and pneumonectomy groups, whatever the statistical method used,” Dr. Pagès and his coauthors wrote.
The investigators had no financial relationships to disclose.
Key clinical point: Sleeve lobectomy for non–small cell lung cancer may lead to higher rates of overall and disease-free survival vs. pneumonectomy.
Major finding: Overall postoperative mortality was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group.
Data source: An analysis of 941 sleeve lobectomy and 5,318 pneumonectomy procedures from 2005 to 2014 in the nationwide French database Epithor.
Disclosures: Dr. Pagès has received research grants from the Nuovo-Soldati Foundation for Cancer Research and the French Society of Thoracic and Cardiovascular Surgery, on whose behalf the study was performed. Dr. Pagès and his coauthors had no financial relationships to disclose.
Esophageal cancers: Apples and oranges wrongly lumped together
Genomic analysis suggests that esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are two separate diseases that should not be combined in clinical trials and may benefit from different treatments, according to the results of a molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
The comprehensive molecular analysis comprised 164 esophageal tumors, 359 gastric adenocarcinomas, and 36 additional adenocarcinomas spanning the gastroesophageal junction.
The results of their analysis “call into question the premise of envisioning esophageal carcinoma as a single entity” and “argue against approaches that combine EAC and ESCC for clinical trials of neoadjuvant, adjuvant, or systemic therapies,” wrote the members of The Cancer Genome Atlas Research Network under the coordination of the National Cancer Institute and the National Human Genome Research Institute project.
The researchers evaluated the 164 esophageal carcinomas using integrated clustering of somatic copy number aberrations, DNA methylation, mRNA, and microRNA expression.
Gene expression analysis showed EACs had increased E-cadherin (CDH1) signaling and upregulation of ARF6 and FOXA pathways, which regulate E-cadherin. In contrast, ESCCs showed upregulation of Wnt, syndecan; p63 pathways, which are essential for squamous epithelial cell differentiation, were also upregulated. “These data suggest the presence of lineage-specific alterations that drive progression in EACs and ESCCs,” according to the researchers.
Somatic genome alterations showed that many of the same genetic pathways were altered in both EAC and ESCC, but the specific genes affected were dissimilar, suggesting distinct pathophysiologies between the two types of cancer. This could signal the need for different treatment approaches and led the researchers to caution against lumping EAC and ESCC in the same clinical trials.
Molecular subtype analysis of the ESCC cancers showed three molecular subtypes: ESCC1 (50 tumors), ESCC2 (36) and ESCC3 (4), distinguished by their mutation types. ESCC1, for example, was characterized by alterations in the NRF2 pathway, mutations in which are associated with poor prognosis and resistance to chemotherapy.
The three subtypes also showed trends for geographic associations, with Vietnamese patients (the only Asian population studied) showing a predominance of ESCC1 (27/41), and all 4 ESCC3 tumors being derived from United States patients.
The researchers also evaluated the molecular association between ESCC and human papillomavirus (HPV), which has been shown to have a pathogenic role in cervical SCC and head and neck (HN)SCC. They found that ESCC mRNA sequencing showed that ESCC-HPV transcript levels were similar to HPV-negative HNSCC tumors, diminishing the likelihood of an etiological role for HPV in ESCC.
In evaluating EACs in comparison to chromosomal instability (CIN) gastric cancers, the researchers found “clear similarity between chromosomal aberrations” in the two cancer types, with a stronger similarity between EAC and CIN gastric cancers than between EAC and ESCC, further differentiating the two esophageal cancers.
“The notable molecular similarity between EACs and CIN gastric cancers provides indirect support for gastric origin of Barrett’s esophagus and EAC and indicates that we may view GEA [gastroesophageal adenocarcinoma] as a singular entity, analogous to colorectal adenocarcinoma,” the authors added.
A notable anatomic gradient showed up in the progression of DNA methylation as seen from proximal to distal GEA-CIN tumors, with the most frequent hypermethylation seen in EACs, compared with gastric CIN cancers, a significant difference.
“These molecular data show that EAC and ESCC are distinct in their molecular characteristics across all platforms tested. ESCC emerges as a disease more reminiscent of other SCCs than of EAC, which itself bears striking resemblance to CIN gastric cancer,” the researchers concluded.
The authors reported that they had no competing financial interests.
This article published in Nature summarizes an integrated genomic analysis of esophageal cancer with careful comparisons to other cancers in the neighborhood (head and neck, lung, and gastric cancer). While clinically apparent to physicians taking care of esophageal cancer throughout the world, these analyses confirm that esophageal squamous cell cancer and esophageal adenocarcinoma are essentially two different diseases with distinct genomic characteristics. This has an important implication in clinical trial design: These pathologies should not be analyzed together, but instead should be studied distinctly.
In addition to the above major conclusion, several other features deserve to be noted. First, esophageal cancer does not seem to be associated with HPV as the HPV transcript levels in these tumors resemble those in HPV-negative head and neck cancers. Second, there are significant differences in the genomic characteristics of esophageal squamous cell cancer depending on geographic location. Third, esophageal adenocarcinoma is most like one particular molecular variant of gastric cancer (chromosomal instability type) and as one moves from the gastric antrum to the esophagus, there is an enrichment of this type of cancer. Such a gradient is found in methylation patterns as well, suggesting a similar cell of origin between gastric and esophageal cancers.
This study brings into focus the overarching theme that cancers may soon be treated based on molecular characteristics rather than anatomic location and clinical trials may have to be grouped based on genetic changes rather than organ systems.
Sai Yendamuri, MD, FACS, is an attending surgeon at the department of thoracic surgery, and director, Thoracic Surgery Research Laboratory, and an associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y.
This article published in Nature summarizes an integrated genomic analysis of esophageal cancer with careful comparisons to other cancers in the neighborhood (head and neck, lung, and gastric cancer). While clinically apparent to physicians taking care of esophageal cancer throughout the world, these analyses confirm that esophageal squamous cell cancer and esophageal adenocarcinoma are essentially two different diseases with distinct genomic characteristics. This has an important implication in clinical trial design: These pathologies should not be analyzed together, but instead should be studied distinctly.
In addition to the above major conclusion, several other features deserve to be noted. First, esophageal cancer does not seem to be associated with HPV as the HPV transcript levels in these tumors resemble those in HPV-negative head and neck cancers. Second, there are significant differences in the genomic characteristics of esophageal squamous cell cancer depending on geographic location. Third, esophageal adenocarcinoma is most like one particular molecular variant of gastric cancer (chromosomal instability type) and as one moves from the gastric antrum to the esophagus, there is an enrichment of this type of cancer. Such a gradient is found in methylation patterns as well, suggesting a similar cell of origin between gastric and esophageal cancers.
This study brings into focus the overarching theme that cancers may soon be treated based on molecular characteristics rather than anatomic location and clinical trials may have to be grouped based on genetic changes rather than organ systems.
Sai Yendamuri, MD, FACS, is an attending surgeon at the department of thoracic surgery, and director, Thoracic Surgery Research Laboratory, and an associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y.
This article published in Nature summarizes an integrated genomic analysis of esophageal cancer with careful comparisons to other cancers in the neighborhood (head and neck, lung, and gastric cancer). While clinically apparent to physicians taking care of esophageal cancer throughout the world, these analyses confirm that esophageal squamous cell cancer and esophageal adenocarcinoma are essentially two different diseases with distinct genomic characteristics. This has an important implication in clinical trial design: These pathologies should not be analyzed together, but instead should be studied distinctly.
In addition to the above major conclusion, several other features deserve to be noted. First, esophageal cancer does not seem to be associated with HPV as the HPV transcript levels in these tumors resemble those in HPV-negative head and neck cancers. Second, there are significant differences in the genomic characteristics of esophageal squamous cell cancer depending on geographic location. Third, esophageal adenocarcinoma is most like one particular molecular variant of gastric cancer (chromosomal instability type) and as one moves from the gastric antrum to the esophagus, there is an enrichment of this type of cancer. Such a gradient is found in methylation patterns as well, suggesting a similar cell of origin between gastric and esophageal cancers.
This study brings into focus the overarching theme that cancers may soon be treated based on molecular characteristics rather than anatomic location and clinical trials may have to be grouped based on genetic changes rather than organ systems.
Sai Yendamuri, MD, FACS, is an attending surgeon at the department of thoracic surgery, and director, Thoracic Surgery Research Laboratory, and an associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y.
Genomic analysis suggests that esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are two separate diseases that should not be combined in clinical trials and may benefit from different treatments, according to the results of a molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
The comprehensive molecular analysis comprised 164 esophageal tumors, 359 gastric adenocarcinomas, and 36 additional adenocarcinomas spanning the gastroesophageal junction.
The results of their analysis “call into question the premise of envisioning esophageal carcinoma as a single entity” and “argue against approaches that combine EAC and ESCC for clinical trials of neoadjuvant, adjuvant, or systemic therapies,” wrote the members of The Cancer Genome Atlas Research Network under the coordination of the National Cancer Institute and the National Human Genome Research Institute project.
The researchers evaluated the 164 esophageal carcinomas using integrated clustering of somatic copy number aberrations, DNA methylation, mRNA, and microRNA expression.
Gene expression analysis showed EACs had increased E-cadherin (CDH1) signaling and upregulation of ARF6 and FOXA pathways, which regulate E-cadherin. In contrast, ESCCs showed upregulation of Wnt, syndecan; p63 pathways, which are essential for squamous epithelial cell differentiation, were also upregulated. “These data suggest the presence of lineage-specific alterations that drive progression in EACs and ESCCs,” according to the researchers.
Somatic genome alterations showed that many of the same genetic pathways were altered in both EAC and ESCC, but the specific genes affected were dissimilar, suggesting distinct pathophysiologies between the two types of cancer. This could signal the need for different treatment approaches and led the researchers to caution against lumping EAC and ESCC in the same clinical trials.
Molecular subtype analysis of the ESCC cancers showed three molecular subtypes: ESCC1 (50 tumors), ESCC2 (36) and ESCC3 (4), distinguished by their mutation types. ESCC1, for example, was characterized by alterations in the NRF2 pathway, mutations in which are associated with poor prognosis and resistance to chemotherapy.
The three subtypes also showed trends for geographic associations, with Vietnamese patients (the only Asian population studied) showing a predominance of ESCC1 (27/41), and all 4 ESCC3 tumors being derived from United States patients.
The researchers also evaluated the molecular association between ESCC and human papillomavirus (HPV), which has been shown to have a pathogenic role in cervical SCC and head and neck (HN)SCC. They found that ESCC mRNA sequencing showed that ESCC-HPV transcript levels were similar to HPV-negative HNSCC tumors, diminishing the likelihood of an etiological role for HPV in ESCC.
In evaluating EACs in comparison to chromosomal instability (CIN) gastric cancers, the researchers found “clear similarity between chromosomal aberrations” in the two cancer types, with a stronger similarity between EAC and CIN gastric cancers than between EAC and ESCC, further differentiating the two esophageal cancers.
“The notable molecular similarity between EACs and CIN gastric cancers provides indirect support for gastric origin of Barrett’s esophagus and EAC and indicates that we may view GEA [gastroesophageal adenocarcinoma] as a singular entity, analogous to colorectal adenocarcinoma,” the authors added.
A notable anatomic gradient showed up in the progression of DNA methylation as seen from proximal to distal GEA-CIN tumors, with the most frequent hypermethylation seen in EACs, compared with gastric CIN cancers, a significant difference.
“These molecular data show that EAC and ESCC are distinct in their molecular characteristics across all platforms tested. ESCC emerges as a disease more reminiscent of other SCCs than of EAC, which itself bears striking resemblance to CIN gastric cancer,” the researchers concluded.
The authors reported that they had no competing financial interests.
Genomic analysis suggests that esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are two separate diseases that should not be combined in clinical trials and may benefit from different treatments, according to the results of a molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
The comprehensive molecular analysis comprised 164 esophageal tumors, 359 gastric adenocarcinomas, and 36 additional adenocarcinomas spanning the gastroesophageal junction.
The results of their analysis “call into question the premise of envisioning esophageal carcinoma as a single entity” and “argue against approaches that combine EAC and ESCC for clinical trials of neoadjuvant, adjuvant, or systemic therapies,” wrote the members of The Cancer Genome Atlas Research Network under the coordination of the National Cancer Institute and the National Human Genome Research Institute project.
The researchers evaluated the 164 esophageal carcinomas using integrated clustering of somatic copy number aberrations, DNA methylation, mRNA, and microRNA expression.
Gene expression analysis showed EACs had increased E-cadherin (CDH1) signaling and upregulation of ARF6 and FOXA pathways, which regulate E-cadherin. In contrast, ESCCs showed upregulation of Wnt, syndecan; p63 pathways, which are essential for squamous epithelial cell differentiation, were also upregulated. “These data suggest the presence of lineage-specific alterations that drive progression in EACs and ESCCs,” according to the researchers.
Somatic genome alterations showed that many of the same genetic pathways were altered in both EAC and ESCC, but the specific genes affected were dissimilar, suggesting distinct pathophysiologies between the two types of cancer. This could signal the need for different treatment approaches and led the researchers to caution against lumping EAC and ESCC in the same clinical trials.
Molecular subtype analysis of the ESCC cancers showed three molecular subtypes: ESCC1 (50 tumors), ESCC2 (36) and ESCC3 (4), distinguished by their mutation types. ESCC1, for example, was characterized by alterations in the NRF2 pathway, mutations in which are associated with poor prognosis and resistance to chemotherapy.
The three subtypes also showed trends for geographic associations, with Vietnamese patients (the only Asian population studied) showing a predominance of ESCC1 (27/41), and all 4 ESCC3 tumors being derived from United States patients.
The researchers also evaluated the molecular association between ESCC and human papillomavirus (HPV), which has been shown to have a pathogenic role in cervical SCC and head and neck (HN)SCC. They found that ESCC mRNA sequencing showed that ESCC-HPV transcript levels were similar to HPV-negative HNSCC tumors, diminishing the likelihood of an etiological role for HPV in ESCC.
In evaluating EACs in comparison to chromosomal instability (CIN) gastric cancers, the researchers found “clear similarity between chromosomal aberrations” in the two cancer types, with a stronger similarity between EAC and CIN gastric cancers than between EAC and ESCC, further differentiating the two esophageal cancers.
“The notable molecular similarity between EACs and CIN gastric cancers provides indirect support for gastric origin of Barrett’s esophagus and EAC and indicates that we may view GEA [gastroesophageal adenocarcinoma] as a singular entity, analogous to colorectal adenocarcinoma,” the authors added.
A notable anatomic gradient showed up in the progression of DNA methylation as seen from proximal to distal GEA-CIN tumors, with the most frequent hypermethylation seen in EACs, compared with gastric CIN cancers, a significant difference.
“These molecular data show that EAC and ESCC are distinct in their molecular characteristics across all platforms tested. ESCC emerges as a disease more reminiscent of other SCCs than of EAC, which itself bears striking resemblance to CIN gastric cancer,” the researchers concluded.
The authors reported that they had no competing financial interests.
FROM NATURE
Key clinical point:
Major finding: Molecular analysis showed esophageal squamous cell carcinoma is more like other squamous cell carcinomas than esophageal adenocarcinoma, which itself resembles chromosomal-instability gastric cancer.
Data source: A molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
Disclosures: The authors reported that they had no competing financial interests.
More restrictive hemoglobin threshold advised
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
These recommendations are very helpful and are now part of standard ICU care in several centers. Our experience in clinical practice has shown that even patients supported with extracorporeal membrane oxygenation (ECMO) for acute lung failure or as a bridge to lung transplantation on VV ECMO can safely tolerate a lower transfusion threshold (7-8g/dL.) Future well-designed trials are needed to advocate its safety in patients supported with extracorporeal life support technologies.
These recommendations are very helpful and are now part of standard ICU care in several centers. Our experience in clinical practice has shown that even patients supported with extracorporeal membrane oxygenation (ECMO) for acute lung failure or as a bridge to lung transplantation on VV ECMO can safely tolerate a lower transfusion threshold (7-8g/dL.) Future well-designed trials are needed to advocate its safety in patients supported with extracorporeal life support technologies.
These recommendations are very helpful and are now part of standard ICU care in several centers. Our experience in clinical practice has shown that even patients supported with extracorporeal membrane oxygenation (ECMO) for acute lung failure or as a bridge to lung transplantation on VV ECMO can safely tolerate a lower transfusion threshold (7-8g/dL.) Future well-designed trials are needed to advocate its safety in patients supported with extracorporeal life support technologies.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
Embolic protection cut lesions, did not aid neurocognition
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
The 5-day “window” for MRI assessment having been too long was among the study’s limitations, Dr. Kapadia said.
Claret Medical funded the study and Dr. Kapadia’s associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
The authors have demonstrated the safety of cerebral protection systems, but not their clinical benefit in terms of preventing adverse neurological outcomes. As they note, a larger study group might produce a statistical difference. Commentary on the added cost of the device would be helpful to weigh their cost effectiveness.
The authors have demonstrated the safety of cerebral protection systems, but not their clinical benefit in terms of preventing adverse neurological outcomes. As they note, a larger study group might produce a statistical difference. Commentary on the added cost of the device would be helpful to weigh their cost effectiveness.
The authors have demonstrated the safety of cerebral protection systems, but not their clinical benefit in terms of preventing adverse neurological outcomes. As they note, a larger study group might produce a statistical difference. Commentary on the added cost of the device would be helpful to weigh their cost effectiveness.
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
The 5-day “window” for MRI assessment having been too long was among the study’s limitations, Dr. Kapadia said.
Claret Medical funded the study and Dr. Kapadia’s associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.
Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.
However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.
In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).
In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).
The remaining 123 patients underwent TAVR but not MRI in a safety arm of the trial.
The protection devices were placed “without safety concerns” in most patients. The rate of major adverse events with the device was 7.3%, markedly less than the 18.3% prespecified performance goal for this outcome. Total procedure time was lengthened by only 13 minutes when the device was used, and total fluoroscopy time was increased by only 3 minutes. These findings demonstrate the overall safety of using the device, Dr. Kapadia said.
Debris including thrombus with tissue elements, artery wall particles, calcifications, valve tissue, and foreign materials was retrieved from the filters in 99% of patients.
The mean volume of new cerebral lesions in areas of the brain protected by the device was reduced by 42%, compared with that in patients who underwent TAVR without the protection device. However, this reduction was not statistically significant, so the primary efficacy endpoint of the study was not met.
Similarly, neurocognitive testing at 30 days showed that the volume of new lesions correlated with poorer outcomes. However, the difference in neurocognitive function between the intervention group and the control group did not reach statistical significance.
The 5-day “window” for MRI assessment having been too long was among the study’s limitations, Dr. Kapadia said.
Claret Medical funded the study and Dr. Kapadia’s associates reported numerous ties to industry sources. The meeting was sponsored by the Cardiovascular Research Foundation.
Cerebral protection in TAVI cuts ischemic lesions
In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.
The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.
Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.
They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.
The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.
In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).
Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).
However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).
It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.
The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.
The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.
Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.
This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.
This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
As there was no significant difference in clinical neurological outcomes related to use of a filter device, although there was significantly fewer and smaller brain lesions in the stroke group, one is left to conclude that the majority of MRI findings after TAVI are not clinically relevant. Is the added cost of a cerebral protection device cost effective given the equivalent neurological outcomes in the both groups?
As there was no significant difference in clinical neurological outcomes related to use of a filter device, although there was significantly fewer and smaller brain lesions in the stroke group, one is left to conclude that the majority of MRI findings after TAVI are not clinically relevant. Is the added cost of a cerebral protection device cost effective given the equivalent neurological outcomes in the both groups?
As there was no significant difference in clinical neurological outcomes related to use of a filter device, although there was significantly fewer and smaller brain lesions in the stroke group, one is left to conclude that the majority of MRI findings after TAVI are not clinically relevant. Is the added cost of a cerebral protection device cost effective given the equivalent neurological outcomes in the both groups?
In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.
The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.
Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.
They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.
The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.
In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).
Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).
However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).
It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.
The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.
The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.
Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.
This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.
This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.
The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.
Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.
They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.
The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.
In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).
Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).
However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).
It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.
The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.
The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.
Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.
This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.
This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
‘Stepping’ up robotic lobectomy instruction
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, FCCP, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed.
“We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said. 
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said.
“A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved.
For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
This in an interesting and clinically relevant study given the emphasis many institutions have placed on becoming “robotic” centers of excellence. The overall cost effectiveness of robotic surgery from a public policy standpoint remains a matter of intense study given the scarcity of resources in many health-care settings.
This in an interesting and clinically relevant study given the emphasis many institutions have placed on becoming “robotic” centers of excellence. The overall cost effectiveness of robotic surgery from a public policy standpoint remains a matter of intense study given the scarcity of resources in many health-care settings.
This in an interesting and clinically relevant study given the emphasis many institutions have placed on becoming “robotic” centers of excellence. The overall cost effectiveness of robotic surgery from a public policy standpoint remains a matter of intense study given the scarcity of resources in many health-care settings.
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, FCCP, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed.
“We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said.
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said.
“A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved.
For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, FCCP, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed.
“We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said.
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said.
“A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved.
For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
TAVR valve durability supported in large follow-up
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up. 
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
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The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
The data reported by Dr. Douglas are very important and very reassuring. It isn’t easy to evaluate long-term results in patients who underwent TAVR in the early days because that population of patients was old and at very high risk. Even when patients had successful procedures their longevity wasn’t long. Only about 10% of the starting population of 2,482 patients in Dr. Douglas’ study actually had echocardiography done after 5 years. To assess durability you need longer-term echo follow-up, but it will be very challenging to have enough patients to have statistical power to do that.
I am not nervous about long-term durability of TAVR in octogenarian patients, the most typical age for TAVR patients today and since we began using it. Durability is more of an issue for patients who are 75 or younger, and we will need data from 7- to 10-year follow-up of younger patients to have a reasonable answer. Younger patients who undergo TAVR may face more of a threat from valve deterioration simply because of their longer life expectancy. In addition, with surgical valves we know that younger age is one of the strongest predictors of valve degeneration.
Danny Dvir, MD , is an interventional cardiologist at the University of Washington in Seattle. He has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. He made these comments in an interview.
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up.
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – First-generation, balloon-expandable transcatheter aortic valves had a less than 1% rate of valve failure in planned echocardiography examinations during follow-up that extended as long as 5 years after valve placement in more than 2,400 patients, a demonstration of durability that experts uniformly called “reassuring.”
This finding from patients who underwent transcatheter aortic valve replacement (TAVR) in the first U.S. pivotal trial for these devices, PARTNER 1 parts A and B, and during the subsequent continued-access program at PARTNER 1 study sites, represents the largest and longest systematic ultrasound follow-up of TAVR patients, Pamela S. Douglas, MD, said at the Transcatheter Cardiovascular Therapeutics annual meeting.
This evaluation of 2,404 TAVR patients in the PARTNER 1 trial examined by echocardiography and encompassing 6,493 patient-years of follow-up is the “largest core-lab based study of transcatheter heart valves to date. These data demonstrate excellent durability of transcatheter heart valves, suggesting that the low 5-year survival observed in this cohort is not related to adverse hemodynamics or transcatheter heart valve deterioration,” said Dr. Douglas, professor of medicine at Duke University, Durham, N.C.
Her findings showed that out of the 2,482 patients treated with TAVR (and including those without echo follow-up) either in the trial or during the continued access program and followed for a median of 2.9 years and an average of 2.6 years, 20 patients (0.8%) required a reintervention. Four of these 20 patients (0.2% of the total cohort) showed a “classic pattern” of aortic valve deterioration marked by an increased valve pressure gradient and a reduced valve area, she reported.
“Reintervention was rare, became less frequent over time, and was usually not due to structural deterioration of the transcatheter heart valve,” she said. But Dr. Douglas also cautioned that among the patients who received the first-generation, balloon expandable Sapien valve in this cohort, just 39% survived to 5 years, and a mere 282 patients (11%) actually underwent echocardiographic examination at 5 years.
“This is one of several steps we need to take to figure out the durability of transcatheter valves,” said Jeffrey J. Popma, MD, professor of medicine and an interventional cardiologist at Beth Israel Deaconess Medical Center, Boston. He noted that data are needed from follow-up periods of 8 or 10 years, but these data will not be available until intermediate- or low-risk patients undergo TAVR in controlled circumstances and have long-term follow-up.
“Ten-year follow-up data will essentially be impossible” for the high-risk or inoperable patients treated with TAVR in the PARTNER 1 trial, which focused on the sickest patients with aortic stenosis, said Dr. Popma, lead investigator for several studies of TAVR using self-expanding aortic valves and marketed as CoreValve devices.
“We obviously need to follow patients longer. The 5-year results look terrific, and so very reassuring, but we need to keep an eye on this as we move TAVR into less sick and younger patients,” said Dr. Robert O. Bonow, professor of cardiology at Northwestern University, Chicago. “Durability is the remaining frontier in terms of moving TAVR into younger patients,” Dr. Bonow said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These data continue to show that “transcatheter valves have looked hemodynamically superior to surgically-placed valves with respect to the VARC (Valve Academic Research Consortium)–2 criteria” for prosthetic valve function, Dr. Popma noted. “I think the benefits of surgical valves have been overstated and the benefits of transcatheter valves understated,” he said.
“Surgical valves have not been held to the same [very demanding] standard as transcatheter valves,” Dr. Douglas agreed.
The data Dr. Douglas reported contrast with longer-term follow-up reported in May 2016 for 378 patients who underwent TAVR at either of two pioneering centers in a retrospective review. Those data suggested a valve degeneration rate of about 50% after 8 years, Danny Dvir, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions. Speaking recently in an interview, Dr. Dvir acknowledged some of the challenges in trying to derive valve durability information from a relatively small number of very-high-risk patients who underwent TAVR very early during development of the procedure.
Some TAVR experts have also questioned the criteria that Dr. Dvir used to identify valve structural valve degeneration for this analysis. “The criteria he used were much more stringent that the criteria we have used to assess surgically-placed valves,” said Michael J. Reardon, MD, professor of cardiovascular surgery at Houston Methodist Hospital. “If surgically-placed aortic valves were subjected to the same criteria Dr. Dvir applied then they would perform even worse,” Dr. Reardon said in an interview.
PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
[email protected]
On Twitter @mitchelzoler
AT TCT 2016
Key clinical point:
Major finding: During median follow-up of 2.9 years, 0.2% of patients had valves with classic hemodynamic signs of valve deterioration.
Data source: A total of 2,482 TAVR patients either enrolled in the PARTNER 1 trial or who underwent TAVR during a continued access program.
Disclosures: PARTNER 1 was sponsored by Edwards Lifesciences, the company that had marketed the Sapien first-generation, balloon expandable TAVR system. Dr. Douglas has received research support from Edwards. Dr. Bonow had no disclosures. Dr. Popma has been the lead investigator for several studies of a self-expanding TAVR system sponsored by Medtronic, and he has also received research funding from several other companies, has been a consultant to Boston Scientific and Direct Flow, and owns equity in Direct Flow. Dr. Dvir has been a consultant to and received research support from Edwards, Medtronic, and St. Jude. Dr. Reardon has been a consultant to Medtronic.
Can bioprosthetics work for large airway defects?
Large and complex airway defects that primary repair cannot fully close require alternative surgical approaches and techniques that are far more difficult to perform, but bioprosthetic materials may be an option to repair large tracheal and bronchial defects that has achieved good results, without postoperative death or defect recurrence, in a small cohort of patients at Massachusetts General Hospital, in Boston.
Brooks Udelsman, MD, and his coauthors reported their results of bioprosthetic repair of central airway defects in eight patients in the Journal of Thoracic and Cardiovascular Surgery (2016 Nov;152:1388-97). “Although our results are derived from a limited number of heterogeneous patients, they suggest that closure of noncircumferential large airway defects with bioprosthetic materials is feasible, safe and reliable,” Dr. Udelsman said. He previously reported the results at the annual meeting of the American Association for Thoracic Surgery, May 14-18, 2016, in Baltimore.
These complex defects typically exceed 5 cm and can involve communication with the esophagus. For repair of smaller defects, surgeons can use a more conventional approach that involves neck flexion, laryngeal release, airway mobilization, and hilar release, but in larger defects, these techniques increase the risk of too much tension on the anastomosis and dehiscence along with airway failure. Large and complex defects occur in patients who have had a previous airway operation or radiation exposure, requiring alternative strategies, the researchers wrote. “Patients in this rare category should be referred to a high-volume center for careful evaluation by a surgeon experienced in complex airway reconstruction before the decision to abandon primary repair is made,” he said. Among the advantages that bioprosthetic materials have over synthetic materials for airway defect repair are easier handling, minimal immunogenic response, and potential for tissue ingrowth, Dr. Udelsman and his coauthors said.
All eight patients in this study, who underwent repair from 2008 to 2015, had significant comorbidities, including previous surgery of the trachea, esophagus, or thyroid. The etiology of the airway defect included HIV-AIDS–associated esophagitis, malignancy, mesh erosion, and complications from extended intubation. Three patients had previous radiation therapy to the neck or chest. Five patients had defects localized to the membranous tracheal wall, two had defects of the mainstem bronchus or bronchus intermedius, and one patient had a defect of the anterior wall of the trachea.
Dr. Udelsman and his coauthors used both aortic homograft and acellular dermal matrix to repair large defects. Their experience confirmed previous reports of the formation of granulation tissue with aortic autografts, underscoring the importance of frequent bronchoscopy and debridement when necessary. And while previous reports have claimed human acellular dermis resists granulation formation, that wasn’t the case in this study. “The exact histologic basis of bioprosthetic incorporation and reepithelialization in these patients is still elusive and will require further study,” the researchers said.
This study also employed the controversial muscle buttress repair in six patients, which helped, at least theoretically, to secure the repairs when leaks occur, to separate suture lines when both the airway and esophagus were repaired and to support the bioprosthetic material to prevent tissue softening, Dr. Udelsman and his coauthors said.
Postoperative examinations confirmed that the operations successfully closed the airway defects in all eight patients. Long term, most resumed oral intake, but three did not for various reasons: one had a pharyngostomy; another had neurocognitive issues preoperatively; and a third with a tracheoesophageal fistula repair and cervical esophagostomy could resume oral intake but depended on tube feeds to meet caloric needs.
All patients developed granulation at the repair site, two of whom required further debridement and one who underwent balloon dilation. Pneumonia was the most common complication within 30 days of surgery, occurring in two patients. Three patients died within 120 days from metastatic disease, and a fourth patient progressed to end-stage AIDS 6 years after the operation and eventually died.
Dr. Udelsman and his coauthors reported having no financial disclosures.
In his invited commentary, Raja Flores, MD, of Mount Sinai Health System in New York said this study demonstrated “modest success” with bioprosthetic materials for repair of large airway deficits – the same level of success he ascribes to human studies of other surgical approaches to large airway deficits (J Thorac Cardiovasc Surg. 2016 Nov;152:1233-4).
But progress has been slow and animal studies of large airway deficit repair have been “wastefully repetitive” without any advances. “We must build on what these human studies have taught us and not continue unsuccessfully to reinvent the same malfunctioning [airways],” Dr. Flores said.
When surgeons encounter such patients, surgery isn’t necessary for their survival, Dr. Flores said. “T-tubes work just fine.” The goal is to improve their quality of life. “Unless we can provide a reliable, long-lasting solution, an unpredictable life-threatening experimental surgical intervention is not justified to treat a stable, functional patient,” he said.
And while Dr. Udelsman and his colleagues have shown “some progress” in their study, he cautioned surgeons to heed the words of a tracheal surgery pioneer Hermes Grillo, MD, at Boston’s Massachusetts General Hospital and Harvard Medical School: “Success has been announced episodically over the decades in each of these categories, but thus far no one replacement method has held for the long term in any safe and practicable manner.” Dr. Flores added: “This still holds true today.”
Dr. Flores reported having no financial disclosures.
In his invited commentary, Raja Flores, MD, of Mount Sinai Health System in New York said this study demonstrated “modest success” with bioprosthetic materials for repair of large airway deficits – the same level of success he ascribes to human studies of other surgical approaches to large airway deficits (J Thorac Cardiovasc Surg. 2016 Nov;152:1233-4).
But progress has been slow and animal studies of large airway deficit repair have been “wastefully repetitive” without any advances. “We must build on what these human studies have taught us and not continue unsuccessfully to reinvent the same malfunctioning [airways],” Dr. Flores said.
When surgeons encounter such patients, surgery isn’t necessary for their survival, Dr. Flores said. “T-tubes work just fine.” The goal is to improve their quality of life. “Unless we can provide a reliable, long-lasting solution, an unpredictable life-threatening experimental surgical intervention is not justified to treat a stable, functional patient,” he said.
And while Dr. Udelsman and his colleagues have shown “some progress” in their study, he cautioned surgeons to heed the words of a tracheal surgery pioneer Hermes Grillo, MD, at Boston’s Massachusetts General Hospital and Harvard Medical School: “Success has been announced episodically over the decades in each of these categories, but thus far no one replacement method has held for the long term in any safe and practicable manner.” Dr. Flores added: “This still holds true today.”
Dr. Flores reported having no financial disclosures.
In his invited commentary, Raja Flores, MD, of Mount Sinai Health System in New York said this study demonstrated “modest success” with bioprosthetic materials for repair of large airway deficits – the same level of success he ascribes to human studies of other surgical approaches to large airway deficits (J Thorac Cardiovasc Surg. 2016 Nov;152:1233-4).
But progress has been slow and animal studies of large airway deficit repair have been “wastefully repetitive” without any advances. “We must build on what these human studies have taught us and not continue unsuccessfully to reinvent the same malfunctioning [airways],” Dr. Flores said.
When surgeons encounter such patients, surgery isn’t necessary for their survival, Dr. Flores said. “T-tubes work just fine.” The goal is to improve their quality of life. “Unless we can provide a reliable, long-lasting solution, an unpredictable life-threatening experimental surgical intervention is not justified to treat a stable, functional patient,” he said.
And while Dr. Udelsman and his colleagues have shown “some progress” in their study, he cautioned surgeons to heed the words of a tracheal surgery pioneer Hermes Grillo, MD, at Boston’s Massachusetts General Hospital and Harvard Medical School: “Success has been announced episodically over the decades in each of these categories, but thus far no one replacement method has held for the long term in any safe and practicable manner.” Dr. Flores added: “This still holds true today.”
Dr. Flores reported having no financial disclosures.
Large and complex airway defects that primary repair cannot fully close require alternative surgical approaches and techniques that are far more difficult to perform, but bioprosthetic materials may be an option to repair large tracheal and bronchial defects that has achieved good results, without postoperative death or defect recurrence, in a small cohort of patients at Massachusetts General Hospital, in Boston.
Brooks Udelsman, MD, and his coauthors reported their results of bioprosthetic repair of central airway defects in eight patients in the Journal of Thoracic and Cardiovascular Surgery (2016 Nov;152:1388-97). “Although our results are derived from a limited number of heterogeneous patients, they suggest that closure of noncircumferential large airway defects with bioprosthetic materials is feasible, safe and reliable,” Dr. Udelsman said. He previously reported the results at the annual meeting of the American Association for Thoracic Surgery, May 14-18, 2016, in Baltimore.
These complex defects typically exceed 5 cm and can involve communication with the esophagus. For repair of smaller defects, surgeons can use a more conventional approach that involves neck flexion, laryngeal release, airway mobilization, and hilar release, but in larger defects, these techniques increase the risk of too much tension on the anastomosis and dehiscence along with airway failure. Large and complex defects occur in patients who have had a previous airway operation or radiation exposure, requiring alternative strategies, the researchers wrote. “Patients in this rare category should be referred to a high-volume center for careful evaluation by a surgeon experienced in complex airway reconstruction before the decision to abandon primary repair is made,” he said. Among the advantages that bioprosthetic materials have over synthetic materials for airway defect repair are easier handling, minimal immunogenic response, and potential for tissue ingrowth, Dr. Udelsman and his coauthors said.
All eight patients in this study, who underwent repair from 2008 to 2015, had significant comorbidities, including previous surgery of the trachea, esophagus, or thyroid. The etiology of the airway defect included HIV-AIDS–associated esophagitis, malignancy, mesh erosion, and complications from extended intubation. Three patients had previous radiation therapy to the neck or chest. Five patients had defects localized to the membranous tracheal wall, two had defects of the mainstem bronchus or bronchus intermedius, and one patient had a defect of the anterior wall of the trachea.
Dr. Udelsman and his coauthors used both aortic homograft and acellular dermal matrix to repair large defects. Their experience confirmed previous reports of the formation of granulation tissue with aortic autografts, underscoring the importance of frequent bronchoscopy and debridement when necessary. And while previous reports have claimed human acellular dermis resists granulation formation, that wasn’t the case in this study. “The exact histologic basis of bioprosthetic incorporation and reepithelialization in these patients is still elusive and will require further study,” the researchers said.
This study also employed the controversial muscle buttress repair in six patients, which helped, at least theoretically, to secure the repairs when leaks occur, to separate suture lines when both the airway and esophagus were repaired and to support the bioprosthetic material to prevent tissue softening, Dr. Udelsman and his coauthors said.
Postoperative examinations confirmed that the operations successfully closed the airway defects in all eight patients. Long term, most resumed oral intake, but three did not for various reasons: one had a pharyngostomy; another had neurocognitive issues preoperatively; and a third with a tracheoesophageal fistula repair and cervical esophagostomy could resume oral intake but depended on tube feeds to meet caloric needs.
All patients developed granulation at the repair site, two of whom required further debridement and one who underwent balloon dilation. Pneumonia was the most common complication within 30 days of surgery, occurring in two patients. Three patients died within 120 days from metastatic disease, and a fourth patient progressed to end-stage AIDS 6 years after the operation and eventually died.
Dr. Udelsman and his coauthors reported having no financial disclosures.
Large and complex airway defects that primary repair cannot fully close require alternative surgical approaches and techniques that are far more difficult to perform, but bioprosthetic materials may be an option to repair large tracheal and bronchial defects that has achieved good results, without postoperative death or defect recurrence, in a small cohort of patients at Massachusetts General Hospital, in Boston.
Brooks Udelsman, MD, and his coauthors reported their results of bioprosthetic repair of central airway defects in eight patients in the Journal of Thoracic and Cardiovascular Surgery (2016 Nov;152:1388-97). “Although our results are derived from a limited number of heterogeneous patients, they suggest that closure of noncircumferential large airway defects with bioprosthetic materials is feasible, safe and reliable,” Dr. Udelsman said. He previously reported the results at the annual meeting of the American Association for Thoracic Surgery, May 14-18, 2016, in Baltimore.
These complex defects typically exceed 5 cm and can involve communication with the esophagus. For repair of smaller defects, surgeons can use a more conventional approach that involves neck flexion, laryngeal release, airway mobilization, and hilar release, but in larger defects, these techniques increase the risk of too much tension on the anastomosis and dehiscence along with airway failure. Large and complex defects occur in patients who have had a previous airway operation or radiation exposure, requiring alternative strategies, the researchers wrote. “Patients in this rare category should be referred to a high-volume center for careful evaluation by a surgeon experienced in complex airway reconstruction before the decision to abandon primary repair is made,” he said. Among the advantages that bioprosthetic materials have over synthetic materials for airway defect repair are easier handling, minimal immunogenic response, and potential for tissue ingrowth, Dr. Udelsman and his coauthors said.
All eight patients in this study, who underwent repair from 2008 to 2015, had significant comorbidities, including previous surgery of the trachea, esophagus, or thyroid. The etiology of the airway defect included HIV-AIDS–associated esophagitis, malignancy, mesh erosion, and complications from extended intubation. Three patients had previous radiation therapy to the neck or chest. Five patients had defects localized to the membranous tracheal wall, two had defects of the mainstem bronchus or bronchus intermedius, and one patient had a defect of the anterior wall of the trachea.
Dr. Udelsman and his coauthors used both aortic homograft and acellular dermal matrix to repair large defects. Their experience confirmed previous reports of the formation of granulation tissue with aortic autografts, underscoring the importance of frequent bronchoscopy and debridement when necessary. And while previous reports have claimed human acellular dermis resists granulation formation, that wasn’t the case in this study. “The exact histologic basis of bioprosthetic incorporation and reepithelialization in these patients is still elusive and will require further study,” the researchers said.
This study also employed the controversial muscle buttress repair in six patients, which helped, at least theoretically, to secure the repairs when leaks occur, to separate suture lines when both the airway and esophagus were repaired and to support the bioprosthetic material to prevent tissue softening, Dr. Udelsman and his coauthors said.
Postoperative examinations confirmed that the operations successfully closed the airway defects in all eight patients. Long term, most resumed oral intake, but three did not for various reasons: one had a pharyngostomy; another had neurocognitive issues preoperatively; and a third with a tracheoesophageal fistula repair and cervical esophagostomy could resume oral intake but depended on tube feeds to meet caloric needs.
All patients developed granulation at the repair site, two of whom required further debridement and one who underwent balloon dilation. Pneumonia was the most common complication within 30 days of surgery, occurring in two patients. Three patients died within 120 days from metastatic disease, and a fourth patient progressed to end-stage AIDS 6 years after the operation and eventually died.
Dr. Udelsman and his coauthors reported having no financial disclosures.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Bioprosthetic materials show progress for reconstruction of large airway defects.
Major finding: Airway defects were successfully closed in all patients, with no postoperative deaths or recurrence of airway defect.
Data source: Eight patients who underwent closure of complex central airway defects with bioprosthetic materials between 2008 and 2015.
Disclosures: Dr. Udelsman and coauthors reported having no relevant financial disclosures.