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Injectable nimodipine does not improve outcomes of subarachnoid hemorrhage
HONOLULU – according to a study presented at the International Stroke Conference sponsored by the American Heart Association. However, the treatment does reduce the rate of angiographic vasospasm significantly and does not raise significant safety concerns.
Approximately 70% of patients with subarachnoid hemorrhage develop vasospasm, which can in turn cause delayed cerebral ischemia. The only evidence-based treatment for ischemia of the brain resulting from vasospasm is nimodipine, which has been the standard of care for more than a decade.
EG-1962 was developed to deliver higher amounts of nimodipine to the CNS and spastic vessels than oral nimodipine. The formulation contains 50-mcm particles of nimodipine combined with a biodegradable polymer. Pharmacokinetic studies indicate that EG-1962 successfully delivers higher amounts of nimodipine to the CNS than the oral formulation does.
A multisite, phase 3 trial
Stephan A. Mayer, MD, William T. Gossett Endowed Chair of Neurology at the Henry Ford Health System in Detroit, presented the trial results. He and his colleagues conducted NEWTON2, a phase 3 trial to evaluate the safety and efficacy of a single 600-mg intraventricular dose of EG-1962 in patients with aneurysmal subarachnoid hemorrhage, compared with those of oral nimodipine. Eligible participants had a World Federation of Neurosurgeons Score (WFNS) of 2-4, Glasgow Coma Scale scores of 7-14, and an indication for placement of an external ventricular drain (such as hydrocephalus). All patients had their aneurysms clipped or coiled.
On the first day after the operation, the investigators randomized patients in equal groups to EG-1962 plus oral placebo or oral nimodipine plus placebo injection. Patients in the EG-1962 arm received a 600-mg injection of nimodipine into the ventricular system. The primary endpoint was the proportion of subjects with an extended Glasgow Outcome Scale (eGOS) score of 6-8 (that is, minimal or mild disability) at day 90. The main secondary endpoint was the proportion of subjects with a Montreal Cognitive Assessment (MOCA) score of 26 or greater (indicating no important cognitive disability) at day 90. Safety outcomes included cerebral infarction, hypotension, and ventriculitis.
Dr. Mayer and his colleagues conducted the study at 65 centers in 11 countries. They planned to enroll 374 patients and conduct an interim analysis after the first 210 participants had their 90-day follow-up. An independent data monitoring committee reviewed the safety data as it was collected. The investigators stopped the study for futility after the preplanned interim analysis was completed.
The challenge of identifying responders
The two study arms were well matched on age and gender. The proportion of patients with poor WFNS was 45% in the EG-1962 arm and 53% in the oral nimodipine arm.
The rate of any vasospasm (such as symptomatic or by imaging) was 56% in the intervention group and 70% in the oral nimodipine group, a statistically significant difference. Follow-up angiography showed vasospasm in 50% of the intervention group, compared with 63% of the oral nimodipine group, which was also statistically significant.
When the investigators examined the primary endpoint, they found that 46% of patients who received EG-1962 had a favorable outcome, compared with 43% of patients who received oral nimodipine, a nonsignificant difference. If the investigators had defined a favorable outcome as an eGOS score of 4 or greater, “there would have been a more favorable effect,” said Dr. Mayer. The investigators found no difference between groups in MOCA score at day 90.
Subgroup analyses produced “puzzling” results, said Dr. Mayer. For example, more patients with poor-grade WFNS had a favorable outcome at 3 months in the EG-1962 group than in the nimodipine group, but fewer patients with good-grade WFNS had a favorable outcome at 3 months in the EG-1962 group than in the nimodipine group. In addition, the treatment effect was more evident in the United States than abroad.
The safety analysis indicated a trend toward less rescue therapy – defined as hypertensive therapy or any interventional approach – in the EG-1962 group (27%), compared with the oral nimodipine group (35%). The rate of hypotension was slightly lower in the EG-1962 group. The rates of treatment-emergent serious adverse events and hydrocephalus were not significantly different between groups.
The results may encourage neurologists to treat “extremely sick patients with highly refractory vasospasms,” said Dr. Mayer. “We have a biologically active agent. The problem is, though, that it’s very hard ... to prove efficacy in trials, because we do not fully understand who the responders were going to be.”
Dr. Mayer reported receiving consulting fees from Edge Therapeutics, the company that developed EG-1962, in the past for activities unrelated to this study. Other investigators are employees of Edge Therapeutics.
SOURCE: Mayer SA et al. ISC 2019, Abstract LB15.
HONOLULU – according to a study presented at the International Stroke Conference sponsored by the American Heart Association. However, the treatment does reduce the rate of angiographic vasospasm significantly and does not raise significant safety concerns.
Approximately 70% of patients with subarachnoid hemorrhage develop vasospasm, which can in turn cause delayed cerebral ischemia. The only evidence-based treatment for ischemia of the brain resulting from vasospasm is nimodipine, which has been the standard of care for more than a decade.
EG-1962 was developed to deliver higher amounts of nimodipine to the CNS and spastic vessels than oral nimodipine. The formulation contains 50-mcm particles of nimodipine combined with a biodegradable polymer. Pharmacokinetic studies indicate that EG-1962 successfully delivers higher amounts of nimodipine to the CNS than the oral formulation does.
A multisite, phase 3 trial
Stephan A. Mayer, MD, William T. Gossett Endowed Chair of Neurology at the Henry Ford Health System in Detroit, presented the trial results. He and his colleagues conducted NEWTON2, a phase 3 trial to evaluate the safety and efficacy of a single 600-mg intraventricular dose of EG-1962 in patients with aneurysmal subarachnoid hemorrhage, compared with those of oral nimodipine. Eligible participants had a World Federation of Neurosurgeons Score (WFNS) of 2-4, Glasgow Coma Scale scores of 7-14, and an indication for placement of an external ventricular drain (such as hydrocephalus). All patients had their aneurysms clipped or coiled.
On the first day after the operation, the investigators randomized patients in equal groups to EG-1962 plus oral placebo or oral nimodipine plus placebo injection. Patients in the EG-1962 arm received a 600-mg injection of nimodipine into the ventricular system. The primary endpoint was the proportion of subjects with an extended Glasgow Outcome Scale (eGOS) score of 6-8 (that is, minimal or mild disability) at day 90. The main secondary endpoint was the proportion of subjects with a Montreal Cognitive Assessment (MOCA) score of 26 or greater (indicating no important cognitive disability) at day 90. Safety outcomes included cerebral infarction, hypotension, and ventriculitis.
Dr. Mayer and his colleagues conducted the study at 65 centers in 11 countries. They planned to enroll 374 patients and conduct an interim analysis after the first 210 participants had their 90-day follow-up. An independent data monitoring committee reviewed the safety data as it was collected. The investigators stopped the study for futility after the preplanned interim analysis was completed.
The challenge of identifying responders
The two study arms were well matched on age and gender. The proportion of patients with poor WFNS was 45% in the EG-1962 arm and 53% in the oral nimodipine arm.
The rate of any vasospasm (such as symptomatic or by imaging) was 56% in the intervention group and 70% in the oral nimodipine group, a statistically significant difference. Follow-up angiography showed vasospasm in 50% of the intervention group, compared with 63% of the oral nimodipine group, which was also statistically significant.
When the investigators examined the primary endpoint, they found that 46% of patients who received EG-1962 had a favorable outcome, compared with 43% of patients who received oral nimodipine, a nonsignificant difference. If the investigators had defined a favorable outcome as an eGOS score of 4 or greater, “there would have been a more favorable effect,” said Dr. Mayer. The investigators found no difference between groups in MOCA score at day 90.
Subgroup analyses produced “puzzling” results, said Dr. Mayer. For example, more patients with poor-grade WFNS had a favorable outcome at 3 months in the EG-1962 group than in the nimodipine group, but fewer patients with good-grade WFNS had a favorable outcome at 3 months in the EG-1962 group than in the nimodipine group. In addition, the treatment effect was more evident in the United States than abroad.
The safety analysis indicated a trend toward less rescue therapy – defined as hypertensive therapy or any interventional approach – in the EG-1962 group (27%), compared with the oral nimodipine group (35%). The rate of hypotension was slightly lower in the EG-1962 group. The rates of treatment-emergent serious adverse events and hydrocephalus were not significantly different between groups.
The results may encourage neurologists to treat “extremely sick patients with highly refractory vasospasms,” said Dr. Mayer. “We have a biologically active agent. The problem is, though, that it’s very hard ... to prove efficacy in trials, because we do not fully understand who the responders were going to be.”
Dr. Mayer reported receiving consulting fees from Edge Therapeutics, the company that developed EG-1962, in the past for activities unrelated to this study. Other investigators are employees of Edge Therapeutics.
SOURCE: Mayer SA et al. ISC 2019, Abstract LB15.
HONOLULU – according to a study presented at the International Stroke Conference sponsored by the American Heart Association. However, the treatment does reduce the rate of angiographic vasospasm significantly and does not raise significant safety concerns.
Approximately 70% of patients with subarachnoid hemorrhage develop vasospasm, which can in turn cause delayed cerebral ischemia. The only evidence-based treatment for ischemia of the brain resulting from vasospasm is nimodipine, which has been the standard of care for more than a decade.
EG-1962 was developed to deliver higher amounts of nimodipine to the CNS and spastic vessels than oral nimodipine. The formulation contains 50-mcm particles of nimodipine combined with a biodegradable polymer. Pharmacokinetic studies indicate that EG-1962 successfully delivers higher amounts of nimodipine to the CNS than the oral formulation does.
A multisite, phase 3 trial
Stephan A. Mayer, MD, William T. Gossett Endowed Chair of Neurology at the Henry Ford Health System in Detroit, presented the trial results. He and his colleagues conducted NEWTON2, a phase 3 trial to evaluate the safety and efficacy of a single 600-mg intraventricular dose of EG-1962 in patients with aneurysmal subarachnoid hemorrhage, compared with those of oral nimodipine. Eligible participants had a World Federation of Neurosurgeons Score (WFNS) of 2-4, Glasgow Coma Scale scores of 7-14, and an indication for placement of an external ventricular drain (such as hydrocephalus). All patients had their aneurysms clipped or coiled.
On the first day after the operation, the investigators randomized patients in equal groups to EG-1962 plus oral placebo or oral nimodipine plus placebo injection. Patients in the EG-1962 arm received a 600-mg injection of nimodipine into the ventricular system. The primary endpoint was the proportion of subjects with an extended Glasgow Outcome Scale (eGOS) score of 6-8 (that is, minimal or mild disability) at day 90. The main secondary endpoint was the proportion of subjects with a Montreal Cognitive Assessment (MOCA) score of 26 or greater (indicating no important cognitive disability) at day 90. Safety outcomes included cerebral infarction, hypotension, and ventriculitis.
Dr. Mayer and his colleagues conducted the study at 65 centers in 11 countries. They planned to enroll 374 patients and conduct an interim analysis after the first 210 participants had their 90-day follow-up. An independent data monitoring committee reviewed the safety data as it was collected. The investigators stopped the study for futility after the preplanned interim analysis was completed.
The challenge of identifying responders
The two study arms were well matched on age and gender. The proportion of patients with poor WFNS was 45% in the EG-1962 arm and 53% in the oral nimodipine arm.
The rate of any vasospasm (such as symptomatic or by imaging) was 56% in the intervention group and 70% in the oral nimodipine group, a statistically significant difference. Follow-up angiography showed vasospasm in 50% of the intervention group, compared with 63% of the oral nimodipine group, which was also statistically significant.
When the investigators examined the primary endpoint, they found that 46% of patients who received EG-1962 had a favorable outcome, compared with 43% of patients who received oral nimodipine, a nonsignificant difference. If the investigators had defined a favorable outcome as an eGOS score of 4 or greater, “there would have been a more favorable effect,” said Dr. Mayer. The investigators found no difference between groups in MOCA score at day 90.
Subgroup analyses produced “puzzling” results, said Dr. Mayer. For example, more patients with poor-grade WFNS had a favorable outcome at 3 months in the EG-1962 group than in the nimodipine group, but fewer patients with good-grade WFNS had a favorable outcome at 3 months in the EG-1962 group than in the nimodipine group. In addition, the treatment effect was more evident in the United States than abroad.
The safety analysis indicated a trend toward less rescue therapy – defined as hypertensive therapy or any interventional approach – in the EG-1962 group (27%), compared with the oral nimodipine group (35%). The rate of hypotension was slightly lower in the EG-1962 group. The rates of treatment-emergent serious adverse events and hydrocephalus were not significantly different between groups.
The results may encourage neurologists to treat “extremely sick patients with highly refractory vasospasms,” said Dr. Mayer. “We have a biologically active agent. The problem is, though, that it’s very hard ... to prove efficacy in trials, because we do not fully understand who the responders were going to be.”
Dr. Mayer reported receiving consulting fees from Edge Therapeutics, the company that developed EG-1962, in the past for activities unrelated to this study. Other investigators are employees of Edge Therapeutics.
SOURCE: Mayer SA et al. ISC 2019, Abstract LB15.
REPORTING FROM ISC 2019
Possible mechanism for fluoroquinolone-induced aortopathy uncovered
A new study finds that patients taking fluoroquinolone antibiotics may be at higher risk of aortopathy in part because of human aortic myofibroblast–mediated extracellular matrix (ECM) dysregulation.
“Emerging evidence supports pharmacologic-associated aortopathy in patients receiving fluoroquinolone [FQ] antibiotics,” said first author David G. Guzzardi, PhD, and his colleagues, citing previous research showing that, “compared with patients receiving amoxicillin antibiotics, those receiving FQ have a 66% higher risk of aneurysm or dissection within a 2-month period after commencing FQ use.”
Based upon such data, the Food and Drug Administration issued a December 2018 warning about the increased risk of ruptures or tears in the aorta with fluoroquinolone antibiotics in certain patients, updating their May 2017 warning regarding “disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system that can occur together in the same patient,” upon exposure to this class of antibiotics. Earlier in 2018, the FDA had reinforced their safety information about serious and potentially fatal low blood sugar levels and mental health side effects with fluoroquinolone antibiotics.
Dr. Guzzardi and his colleagues at the University of Calgary (Alta.) performed a study to attempt to determine the possible cellular mechanisms for the observed aortopathy. In their study published in the Journal of Thoracic and Cardiovascular Surgery, Dr. Guzzardi and his colleagues isolated human aortic myofibroblasts from nine patients with aortopathy who were undergoing elective ascending aortic resection.
Following exposure of cells to FQ, the researchers assessed secreted matrix metalloproteinases relative to tissue inhibitors of matrix metalloproteinases (TIMPs). In addition, they examined ECM degradation by using a three-dimensional gelatin-fluorescein isothiocyanate fluorescence microgel assay. Aortic cellular collagen type I expression following FQ exposure was determined by immunoblotting and immunofluorescent staining. Dr. Guzzardi and his colleagues also looked at cell apoptosis, necrosis, and metabolic viability using two versions of vital staining.
They found that FQ exposure significantly decreased aortic cell TIMP-1 (P less than .004) and TIMP-2 (P less than .0004) protein expression, compared with controls, and the ratio of matrix metalloproteinase 9/TIMP-2 was increased (P less than .01). This suggests an increased capacity for ECM degradation after FQ exposure, according to the researchers.
In addition, FQ exposure attenuated collagen type I expression as assessed by immunoblotting (P less than .002) and immunofluorescence (P less than .02).
“FQ induces human aortic myofibroblast–mediated ECM dysregulation by decreasing TIMP expression and preventing compensatory collagen deposition. These data provide novel insights into the mechanisms that may underlie the clinical association of FQ exposure and increased risk of acute aortic events in the community. Our data suggest cautious use of FQ in selected patient populations with preexistent aortopathy and connective tissue disorders,” the researchers concluded.
In an accompanying editorial, while warning that these are preliminary observations based upon a small number of patients with aortopathy, Ari A. Mennander, MD, PhD, of Tampere (Finland) University, wrote that, “for the first time, the wild theory of fluoroquinolone-associated aortopathy has a molecular hint that is based on collagen degeneration and progression of aortic disease. ... This theory is in line with previous observations revealing antifibrotic activity and decreased collagen-1 protein expression with fluoroquinolones. The enigmatic puzzle of the progression of some aortic events may alarmingly be iatrogenic, and the clinician may wisely consider a prudent use of fluoroquinolones in patients with aortic dilatation.”
The authors and commentators reported that they had no commercial conflicts to disclose.
SOURCE: Guzzardi DG et al. J Thorac Cardiovasc Surg. 2019;157:109-19.
The issue of fluoroquinolones is certainly of concern. I wonder how many of my patients who have suffered a ruptured aneurysm were on one of these drugs? In the last few years, Cipro (ciprofloxacin) and Levaquin (levofloxacin) were commonly used by our family practice and internal medicine colleagues for almost all outpatient infections. It was so common that even my wife, who is not a physician, would request Cipro whenever she had a sneeze. We would also bring large bottles of Cipro every time we went traveling to some exotic destination, reassuring ourselves that the only “runs” we would have would be in the airport trying to catch a flight. A cousin of mine, prescribed Levaquin by a well-meaning physician while he was cruising the Nile River, ruptured his Achilles tendon.
Russell H. Samson, MD, FACS, DFSVS , is a clinical professor of surgery at Florida State University, Sarasota, a senior surgeon at Sarasota Vascular Specialists, and President of the Mote Vascular Foundation.
The issue of fluoroquinolones is certainly of concern. I wonder how many of my patients who have suffered a ruptured aneurysm were on one of these drugs? In the last few years, Cipro (ciprofloxacin) and Levaquin (levofloxacin) were commonly used by our family practice and internal medicine colleagues for almost all outpatient infections. It was so common that even my wife, who is not a physician, would request Cipro whenever she had a sneeze. We would also bring large bottles of Cipro every time we went traveling to some exotic destination, reassuring ourselves that the only “runs” we would have would be in the airport trying to catch a flight. A cousin of mine, prescribed Levaquin by a well-meaning physician while he was cruising the Nile River, ruptured his Achilles tendon.
Russell H. Samson, MD, FACS, DFSVS , is a clinical professor of surgery at Florida State University, Sarasota, a senior surgeon at Sarasota Vascular Specialists, and President of the Mote Vascular Foundation.
The issue of fluoroquinolones is certainly of concern. I wonder how many of my patients who have suffered a ruptured aneurysm were on one of these drugs? In the last few years, Cipro (ciprofloxacin) and Levaquin (levofloxacin) were commonly used by our family practice and internal medicine colleagues for almost all outpatient infections. It was so common that even my wife, who is not a physician, would request Cipro whenever she had a sneeze. We would also bring large bottles of Cipro every time we went traveling to some exotic destination, reassuring ourselves that the only “runs” we would have would be in the airport trying to catch a flight. A cousin of mine, prescribed Levaquin by a well-meaning physician while he was cruising the Nile River, ruptured his Achilles tendon.
Russell H. Samson, MD, FACS, DFSVS , is a clinical professor of surgery at Florida State University, Sarasota, a senior surgeon at Sarasota Vascular Specialists, and President of the Mote Vascular Foundation.
A new study finds that patients taking fluoroquinolone antibiotics may be at higher risk of aortopathy in part because of human aortic myofibroblast–mediated extracellular matrix (ECM) dysregulation.
“Emerging evidence supports pharmacologic-associated aortopathy in patients receiving fluoroquinolone [FQ] antibiotics,” said first author David G. Guzzardi, PhD, and his colleagues, citing previous research showing that, “compared with patients receiving amoxicillin antibiotics, those receiving FQ have a 66% higher risk of aneurysm or dissection within a 2-month period after commencing FQ use.”
Based upon such data, the Food and Drug Administration issued a December 2018 warning about the increased risk of ruptures or tears in the aorta with fluoroquinolone antibiotics in certain patients, updating their May 2017 warning regarding “disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system that can occur together in the same patient,” upon exposure to this class of antibiotics. Earlier in 2018, the FDA had reinforced their safety information about serious and potentially fatal low blood sugar levels and mental health side effects with fluoroquinolone antibiotics.
Dr. Guzzardi and his colleagues at the University of Calgary (Alta.) performed a study to attempt to determine the possible cellular mechanisms for the observed aortopathy. In their study published in the Journal of Thoracic and Cardiovascular Surgery, Dr. Guzzardi and his colleagues isolated human aortic myofibroblasts from nine patients with aortopathy who were undergoing elective ascending aortic resection.
Following exposure of cells to FQ, the researchers assessed secreted matrix metalloproteinases relative to tissue inhibitors of matrix metalloproteinases (TIMPs). In addition, they examined ECM degradation by using a three-dimensional gelatin-fluorescein isothiocyanate fluorescence microgel assay. Aortic cellular collagen type I expression following FQ exposure was determined by immunoblotting and immunofluorescent staining. Dr. Guzzardi and his colleagues also looked at cell apoptosis, necrosis, and metabolic viability using two versions of vital staining.
They found that FQ exposure significantly decreased aortic cell TIMP-1 (P less than .004) and TIMP-2 (P less than .0004) protein expression, compared with controls, and the ratio of matrix metalloproteinase 9/TIMP-2 was increased (P less than .01). This suggests an increased capacity for ECM degradation after FQ exposure, according to the researchers.
In addition, FQ exposure attenuated collagen type I expression as assessed by immunoblotting (P less than .002) and immunofluorescence (P less than .02).
“FQ induces human aortic myofibroblast–mediated ECM dysregulation by decreasing TIMP expression and preventing compensatory collagen deposition. These data provide novel insights into the mechanisms that may underlie the clinical association of FQ exposure and increased risk of acute aortic events in the community. Our data suggest cautious use of FQ in selected patient populations with preexistent aortopathy and connective tissue disorders,” the researchers concluded.
In an accompanying editorial, while warning that these are preliminary observations based upon a small number of patients with aortopathy, Ari A. Mennander, MD, PhD, of Tampere (Finland) University, wrote that, “for the first time, the wild theory of fluoroquinolone-associated aortopathy has a molecular hint that is based on collagen degeneration and progression of aortic disease. ... This theory is in line with previous observations revealing antifibrotic activity and decreased collagen-1 protein expression with fluoroquinolones. The enigmatic puzzle of the progression of some aortic events may alarmingly be iatrogenic, and the clinician may wisely consider a prudent use of fluoroquinolones in patients with aortic dilatation.”
The authors and commentators reported that they had no commercial conflicts to disclose.
SOURCE: Guzzardi DG et al. J Thorac Cardiovasc Surg. 2019;157:109-19.
A new study finds that patients taking fluoroquinolone antibiotics may be at higher risk of aortopathy in part because of human aortic myofibroblast–mediated extracellular matrix (ECM) dysregulation.
“Emerging evidence supports pharmacologic-associated aortopathy in patients receiving fluoroquinolone [FQ] antibiotics,” said first author David G. Guzzardi, PhD, and his colleagues, citing previous research showing that, “compared with patients receiving amoxicillin antibiotics, those receiving FQ have a 66% higher risk of aneurysm or dissection within a 2-month period after commencing FQ use.”
Based upon such data, the Food and Drug Administration issued a December 2018 warning about the increased risk of ruptures or tears in the aorta with fluoroquinolone antibiotics in certain patients, updating their May 2017 warning regarding “disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system that can occur together in the same patient,” upon exposure to this class of antibiotics. Earlier in 2018, the FDA had reinforced their safety information about serious and potentially fatal low blood sugar levels and mental health side effects with fluoroquinolone antibiotics.
Dr. Guzzardi and his colleagues at the University of Calgary (Alta.) performed a study to attempt to determine the possible cellular mechanisms for the observed aortopathy. In their study published in the Journal of Thoracic and Cardiovascular Surgery, Dr. Guzzardi and his colleagues isolated human aortic myofibroblasts from nine patients with aortopathy who were undergoing elective ascending aortic resection.
Following exposure of cells to FQ, the researchers assessed secreted matrix metalloproteinases relative to tissue inhibitors of matrix metalloproteinases (TIMPs). In addition, they examined ECM degradation by using a three-dimensional gelatin-fluorescein isothiocyanate fluorescence microgel assay. Aortic cellular collagen type I expression following FQ exposure was determined by immunoblotting and immunofluorescent staining. Dr. Guzzardi and his colleagues also looked at cell apoptosis, necrosis, and metabolic viability using two versions of vital staining.
They found that FQ exposure significantly decreased aortic cell TIMP-1 (P less than .004) and TIMP-2 (P less than .0004) protein expression, compared with controls, and the ratio of matrix metalloproteinase 9/TIMP-2 was increased (P less than .01). This suggests an increased capacity for ECM degradation after FQ exposure, according to the researchers.
In addition, FQ exposure attenuated collagen type I expression as assessed by immunoblotting (P less than .002) and immunofluorescence (P less than .02).
“FQ induces human aortic myofibroblast–mediated ECM dysregulation by decreasing TIMP expression and preventing compensatory collagen deposition. These data provide novel insights into the mechanisms that may underlie the clinical association of FQ exposure and increased risk of acute aortic events in the community. Our data suggest cautious use of FQ in selected patient populations with preexistent aortopathy and connective tissue disorders,” the researchers concluded.
In an accompanying editorial, while warning that these are preliminary observations based upon a small number of patients with aortopathy, Ari A. Mennander, MD, PhD, of Tampere (Finland) University, wrote that, “for the first time, the wild theory of fluoroquinolone-associated aortopathy has a molecular hint that is based on collagen degeneration and progression of aortic disease. ... This theory is in line with previous observations revealing antifibrotic activity and decreased collagen-1 protein expression with fluoroquinolones. The enigmatic puzzle of the progression of some aortic events may alarmingly be iatrogenic, and the clinician may wisely consider a prudent use of fluoroquinolones in patients with aortic dilatation.”
The authors and commentators reported that they had no commercial conflicts to disclose.
SOURCE: Guzzardi DG et al. J Thorac Cardiovasc Surg. 2019;157:109-19.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
EVAR insights from the GREAT registry
CHICAGO – The Global Registry for Endovascular Aortic Treatment is a unique resource that, although still early in its planned 10-year follow-up period, has already yielded important insights into one of the hottest topics in endovascular repair of abdominal aortic aneurysms: that is, the impact of the proximal aortic neck, Clayton J. Brinster, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
The Global Registry for Endovascular Aortic Treatment (GREAT) is a prospective, observational, real-world registry that enrolled more than 5,000 consecutive patients undergoing endovascular aortic repair (EVAR) in the United States, Europe, Australia, New Zealand, and Brazil before enrollment closed in October 2016.
GREAT is the largest stent graft registry in the world. One of its special features is that it has essentially no exclusion criteria. This enables researchers to compare outcomes in patients undergoing on-label EVAR using devices deployed within the official instructions for use (IFU) to results in real-world practice, which not infrequently entails treatment for nonstandard indications using devices outside the narrowly defined IFU generated via pivotal clinical trials, explained Dr. Brinster, a vascular surgeon at the Ochsner Clinic Foundation in New Orleans.
The biggest limitation of GREAT is that it’s sponsored by Gore and restricted to recipients of GORE thoracic and abdominal stent grafts. However, the registry has an oversight and safety monitoring board that is independent of the company, Dr. Brinster continued.
He highlighted three recently published studies that have utilized early GREAT data to examine the impact on EVAR outcomes of various features of the proximal aortic neck.
Noncylindrical neck anatomy
An international team of investigators analyzed the incidence and impact of noncylindrical neck anatomy, defined as a 2-mm or greater change in diameter over the first 15 mm of proximal aortic neck length. Of 3,077 GREAT participants treated with the Gore Excluder endograft, 1,312, or 43%, had an hourglass, tapered, or conical neck shape that qualified as noncylindrical. Noncylindrical necks were more common in women. Fifteen percent of patients with a noncylindrical neck received the device outside the Excluder IFU, as did 11% with a cylindrical neck.
After an average follow-up of about 20 months, the noncylindrical neck group had a 3.1% rate of device-related intervention, significantly better than the 4.9% rate in patients with a cylindrical neck. In a multivariate regression analysis, female gender and maximum abdominal aortic aneurysm diameter were significant risk factors for device-related or endoleak-specific reintervention; noncylindrical neck morphology was not. Indeed, women were 2.2-fold more likely to require device-related reintervention than men (J Vasc Surg. 2018; 68[6]:1714-24).
Large proximal aortic neck
Of 3,166 consecutive patients in GREAT, 37.6% had a large aortic neck diameter, defined as 25 mm or wider. The rate of 5-year freedom from type Ia endoleak was 96.8% in the large-neck group, significantly less than the 98.6% rate in patients with a normal aortic neck diameter. Of note, rates didn’t diverge until after 2 years of follow-up, emphasizing the need for careful long-term surveillance despite initial technical success.
The 5-year rate of freedom from the primary composite endpoint of type Ia endoleak, reintervention, aortic rupture, or isolated aortic-related mortality was also significantly worse in the large-neck group: 81.3% versus 87%. Moreover, the 5-year survival rate was only 64.6% in the large–aortic neck group, compared with 76.5% in the comparator arm, even though aortic-related mortality didn’t differ between the two groups. “The findings raise the question of whether young patients, with predicted life expectancies exceeding 10 years, should receive standard endovascular intervention if they have large aortic neck diameters at baseline (Eur J Vasc Endovasc Surg. 2018;56[2]:189-99).
Severe neck angulation
Australian investigators wondered if the IFU for the Gore C3 Excluder was overly restrictive in defining abdominal aortic aneurysms with necks greater than 60 degrees as off-label for the device. In the first 1,394 patients enrolled in GREAT, the researchers identified 127 (9.2%) who exhibited more than 60 and less than 140 degrees of neck angulation and didn’t require endoanchors for proximal fixation. Their mean neck angle was 78 degrees, with a mean neck length of 29 mm. Mean graft oversizing was 23.5%, which was also outside the Excluder IFU.
During a median follow-up of 236 days there were 7 type Ia endoleaks, for an incidence of 5.6%. The degree of neck angulation, neck length, and the amount of oversizing were not associated with endoleak (Ann Vasc Surg. 2018;49:152-57). However, Dr. Brinster wants to see longer follow-up data before he is prepared to accept that a mean 23.5% graft oversizing is a benign intervention.
“One must remember that, with that percentage of oversizing in an already abnormal neck, aortic neck dilation could be a significant problem longer term,” the vascular surgeon said.
Dr. Brinster reported having no conflicts regarding his presentation.
bjancin@mdedge.com
CHICAGO – The Global Registry for Endovascular Aortic Treatment is a unique resource that, although still early in its planned 10-year follow-up period, has already yielded important insights into one of the hottest topics in endovascular repair of abdominal aortic aneurysms: that is, the impact of the proximal aortic neck, Clayton J. Brinster, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
The Global Registry for Endovascular Aortic Treatment (GREAT) is a prospective, observational, real-world registry that enrolled more than 5,000 consecutive patients undergoing endovascular aortic repair (EVAR) in the United States, Europe, Australia, New Zealand, and Brazil before enrollment closed in October 2016.
GREAT is the largest stent graft registry in the world. One of its special features is that it has essentially no exclusion criteria. This enables researchers to compare outcomes in patients undergoing on-label EVAR using devices deployed within the official instructions for use (IFU) to results in real-world practice, which not infrequently entails treatment for nonstandard indications using devices outside the narrowly defined IFU generated via pivotal clinical trials, explained Dr. Brinster, a vascular surgeon at the Ochsner Clinic Foundation in New Orleans.
The biggest limitation of GREAT is that it’s sponsored by Gore and restricted to recipients of GORE thoracic and abdominal stent grafts. However, the registry has an oversight and safety monitoring board that is independent of the company, Dr. Brinster continued.
He highlighted three recently published studies that have utilized early GREAT data to examine the impact on EVAR outcomes of various features of the proximal aortic neck.
Noncylindrical neck anatomy
An international team of investigators analyzed the incidence and impact of noncylindrical neck anatomy, defined as a 2-mm or greater change in diameter over the first 15 mm of proximal aortic neck length. Of 3,077 GREAT participants treated with the Gore Excluder endograft, 1,312, or 43%, had an hourglass, tapered, or conical neck shape that qualified as noncylindrical. Noncylindrical necks were more common in women. Fifteen percent of patients with a noncylindrical neck received the device outside the Excluder IFU, as did 11% with a cylindrical neck.
After an average follow-up of about 20 months, the noncylindrical neck group had a 3.1% rate of device-related intervention, significantly better than the 4.9% rate in patients with a cylindrical neck. In a multivariate regression analysis, female gender and maximum abdominal aortic aneurysm diameter were significant risk factors for device-related or endoleak-specific reintervention; noncylindrical neck morphology was not. Indeed, women were 2.2-fold more likely to require device-related reintervention than men (J Vasc Surg. 2018; 68[6]:1714-24).
Large proximal aortic neck
Of 3,166 consecutive patients in GREAT, 37.6% had a large aortic neck diameter, defined as 25 mm or wider. The rate of 5-year freedom from type Ia endoleak was 96.8% in the large-neck group, significantly less than the 98.6% rate in patients with a normal aortic neck diameter. Of note, rates didn’t diverge until after 2 years of follow-up, emphasizing the need for careful long-term surveillance despite initial technical success.
The 5-year rate of freedom from the primary composite endpoint of type Ia endoleak, reintervention, aortic rupture, or isolated aortic-related mortality was also significantly worse in the large-neck group: 81.3% versus 87%. Moreover, the 5-year survival rate was only 64.6% in the large–aortic neck group, compared with 76.5% in the comparator arm, even though aortic-related mortality didn’t differ between the two groups. “The findings raise the question of whether young patients, with predicted life expectancies exceeding 10 years, should receive standard endovascular intervention if they have large aortic neck diameters at baseline (Eur J Vasc Endovasc Surg. 2018;56[2]:189-99).
Severe neck angulation
Australian investigators wondered if the IFU for the Gore C3 Excluder was overly restrictive in defining abdominal aortic aneurysms with necks greater than 60 degrees as off-label for the device. In the first 1,394 patients enrolled in GREAT, the researchers identified 127 (9.2%) who exhibited more than 60 and less than 140 degrees of neck angulation and didn’t require endoanchors for proximal fixation. Their mean neck angle was 78 degrees, with a mean neck length of 29 mm. Mean graft oversizing was 23.5%, which was also outside the Excluder IFU.
During a median follow-up of 236 days there were 7 type Ia endoleaks, for an incidence of 5.6%. The degree of neck angulation, neck length, and the amount of oversizing were not associated with endoleak (Ann Vasc Surg. 2018;49:152-57). However, Dr. Brinster wants to see longer follow-up data before he is prepared to accept that a mean 23.5% graft oversizing is a benign intervention.
“One must remember that, with that percentage of oversizing in an already abnormal neck, aortic neck dilation could be a significant problem longer term,” the vascular surgeon said.
Dr. Brinster reported having no conflicts regarding his presentation.
bjancin@mdedge.com
CHICAGO – The Global Registry for Endovascular Aortic Treatment is a unique resource that, although still early in its planned 10-year follow-up period, has already yielded important insights into one of the hottest topics in endovascular repair of abdominal aortic aneurysms: that is, the impact of the proximal aortic neck, Clayton J. Brinster, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
The Global Registry for Endovascular Aortic Treatment (GREAT) is a prospective, observational, real-world registry that enrolled more than 5,000 consecutive patients undergoing endovascular aortic repair (EVAR) in the United States, Europe, Australia, New Zealand, and Brazil before enrollment closed in October 2016.
GREAT is the largest stent graft registry in the world. One of its special features is that it has essentially no exclusion criteria. This enables researchers to compare outcomes in patients undergoing on-label EVAR using devices deployed within the official instructions for use (IFU) to results in real-world practice, which not infrequently entails treatment for nonstandard indications using devices outside the narrowly defined IFU generated via pivotal clinical trials, explained Dr. Brinster, a vascular surgeon at the Ochsner Clinic Foundation in New Orleans.
The biggest limitation of GREAT is that it’s sponsored by Gore and restricted to recipients of GORE thoracic and abdominal stent grafts. However, the registry has an oversight and safety monitoring board that is independent of the company, Dr. Brinster continued.
He highlighted three recently published studies that have utilized early GREAT data to examine the impact on EVAR outcomes of various features of the proximal aortic neck.
Noncylindrical neck anatomy
An international team of investigators analyzed the incidence and impact of noncylindrical neck anatomy, defined as a 2-mm or greater change in diameter over the first 15 mm of proximal aortic neck length. Of 3,077 GREAT participants treated with the Gore Excluder endograft, 1,312, or 43%, had an hourglass, tapered, or conical neck shape that qualified as noncylindrical. Noncylindrical necks were more common in women. Fifteen percent of patients with a noncylindrical neck received the device outside the Excluder IFU, as did 11% with a cylindrical neck.
After an average follow-up of about 20 months, the noncylindrical neck group had a 3.1% rate of device-related intervention, significantly better than the 4.9% rate in patients with a cylindrical neck. In a multivariate regression analysis, female gender and maximum abdominal aortic aneurysm diameter were significant risk factors for device-related or endoleak-specific reintervention; noncylindrical neck morphology was not. Indeed, women were 2.2-fold more likely to require device-related reintervention than men (J Vasc Surg. 2018; 68[6]:1714-24).
Large proximal aortic neck
Of 3,166 consecutive patients in GREAT, 37.6% had a large aortic neck diameter, defined as 25 mm or wider. The rate of 5-year freedom from type Ia endoleak was 96.8% in the large-neck group, significantly less than the 98.6% rate in patients with a normal aortic neck diameter. Of note, rates didn’t diverge until after 2 years of follow-up, emphasizing the need for careful long-term surveillance despite initial technical success.
The 5-year rate of freedom from the primary composite endpoint of type Ia endoleak, reintervention, aortic rupture, or isolated aortic-related mortality was also significantly worse in the large-neck group: 81.3% versus 87%. Moreover, the 5-year survival rate was only 64.6% in the large–aortic neck group, compared with 76.5% in the comparator arm, even though aortic-related mortality didn’t differ between the two groups. “The findings raise the question of whether young patients, with predicted life expectancies exceeding 10 years, should receive standard endovascular intervention if they have large aortic neck diameters at baseline (Eur J Vasc Endovasc Surg. 2018;56[2]:189-99).
Severe neck angulation
Australian investigators wondered if the IFU for the Gore C3 Excluder was overly restrictive in defining abdominal aortic aneurysms with necks greater than 60 degrees as off-label for the device. In the first 1,394 patients enrolled in GREAT, the researchers identified 127 (9.2%) who exhibited more than 60 and less than 140 degrees of neck angulation and didn’t require endoanchors for proximal fixation. Their mean neck angle was 78 degrees, with a mean neck length of 29 mm. Mean graft oversizing was 23.5%, which was also outside the Excluder IFU.
During a median follow-up of 236 days there were 7 type Ia endoleaks, for an incidence of 5.6%. The degree of neck angulation, neck length, and the amount of oversizing were not associated with endoleak (Ann Vasc Surg. 2018;49:152-57). However, Dr. Brinster wants to see longer follow-up data before he is prepared to accept that a mean 23.5% graft oversizing is a benign intervention.
“One must remember that, with that percentage of oversizing in an already abnormal neck, aortic neck dilation could be a significant problem longer term,” the vascular surgeon said.
Dr. Brinster reported having no conflicts regarding his presentation.
bjancin@mdedge.com
EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM
Getting serious about post-EVAR aortic neck dilation
CHICAGO – Clinically significant aortic neck dilation occurs in one-quarter of patients after endovascular abdominal aortic aneurysm repair and is associated with sharply increased risk for type Ia endoleak, stent migration at the proximal seal zone, continued aneurysmal sack enlargement, and even aneurysm rupture, Jason T. Lee, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
He cited what he considers to be the best-quality systematic review of the literature regarding proximal neck dilation after endovascular aneurysm repair (EVAR), which was conducted by investigators at Paracelsus Medical University in Nuremberg, Germany. The data, he said, speak to the importance of trying to minimize the chances of aortic neck dilation (AND).
The review, which included 26 published studies through 2015 and nearly 10,000 EVAR patients, concluded that AND occurred in 24.6% of these patients. The investigators defined AND as more than 3 mm of dilation, which with an average neck diameter of about 30 mm in all comers, would represent a 10% aortic neck-diameter expansion. The incidence of the composite adverse outcome of type I endoleak, stent migration, and reintervention during a maximum of 9 years of follow-up was 29-fold greater in the AND group than in AND-free patients (J Endovasc Ther. 2017;24[1]:59-67).
Continuing controversy exists regarding the extent to which post-EVAR AND is a manifestation of the underlying aneurysmal process as opposed to an adverse effect caused by the outward radial force applied by the stent. That being said, there are several factors related to AND that are potentially within the vascular interventionalist’s control. Topping the list is aggressive oversizing of self-expanding stent grafts in an effort to obtain an excellent seal, according to Dr. Lee, a professor of surgery at Stanford (Calif.) University.
“The data from multiple series definitely suggests that more than 20% oversizing is correlated with a higher incidence of AND. So maybe the answer is oversizing by more like 10%-15%,” the vascular surgeon said.
Another factor contributing to AND is the overwhelming popularity of self-expanding aortic stent grafts, now utilized in 95% of all EVARS done in the United States. Balloon-expandable stent grafts require much less oversizing – less than 5% – to maintain their diameter post deployment, but they are rarely used. Indeed, the only commercially available balloon-expandable device in the United States is the TriVascular Ovation stent system, which seals the stent graft to the wall of the aorta via polyethylene glycol rather than by radial force.
Intriguingly, Italian investigators have reported that, in a multicenter series of 161 patients who underwent EVAR with the Ovation endograft, no AND occurred at CT scanning done after a minimum of 24 months of follow-up (J Vasc Surg. 2016;63[1]:8-15).
Previous studies of the implications of AND after EVAR have been limited to comparisons of early-generation devices, so Dr. Lee and his coinvestigators conducted a retrospective review of a prospective Stanford database that included 86 patients who underwent elective, uncomplicated infrarenal endovascular abdominal aortic aneurysm repairs using a variety of contemporary stent grafts. Eighty-six percent of patients experienced AND during a median radiologic follow-up of 21.9 months, with a mean 1.3-mm increase at 30 days and 3.3 mm at most recent follow-up. The degree of AND correlated with the amount of oversizing. However, AND didn’t vary significantly by device type, which included the Cook Zenith, Gore Excluder, Medtronic Endurant, and Endologix Powerlink self-expanding stent grafts (Ann Vasc Surg. 2017;43:115-20).
Aortic anatomy also plays a role in AND. Shorter necks with severe angulation have been found to pose a higher risk. Open repair, which entails much less AND than does EVAR, may make more sense in that challenging anatomic situation, according to Dr. Lee.
He reported current research funding from Cook, Gore, and Medtronic.
CHICAGO – Clinically significant aortic neck dilation occurs in one-quarter of patients after endovascular abdominal aortic aneurysm repair and is associated with sharply increased risk for type Ia endoleak, stent migration at the proximal seal zone, continued aneurysmal sack enlargement, and even aneurysm rupture, Jason T. Lee, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
He cited what he considers to be the best-quality systematic review of the literature regarding proximal neck dilation after endovascular aneurysm repair (EVAR), which was conducted by investigators at Paracelsus Medical University in Nuremberg, Germany. The data, he said, speak to the importance of trying to minimize the chances of aortic neck dilation (AND).
The review, which included 26 published studies through 2015 and nearly 10,000 EVAR patients, concluded that AND occurred in 24.6% of these patients. The investigators defined AND as more than 3 mm of dilation, which with an average neck diameter of about 30 mm in all comers, would represent a 10% aortic neck-diameter expansion. The incidence of the composite adverse outcome of type I endoleak, stent migration, and reintervention during a maximum of 9 years of follow-up was 29-fold greater in the AND group than in AND-free patients (J Endovasc Ther. 2017;24[1]:59-67).
Continuing controversy exists regarding the extent to which post-EVAR AND is a manifestation of the underlying aneurysmal process as opposed to an adverse effect caused by the outward radial force applied by the stent. That being said, there are several factors related to AND that are potentially within the vascular interventionalist’s control. Topping the list is aggressive oversizing of self-expanding stent grafts in an effort to obtain an excellent seal, according to Dr. Lee, a professor of surgery at Stanford (Calif.) University.
“The data from multiple series definitely suggests that more than 20% oversizing is correlated with a higher incidence of AND. So maybe the answer is oversizing by more like 10%-15%,” the vascular surgeon said.
Another factor contributing to AND is the overwhelming popularity of self-expanding aortic stent grafts, now utilized in 95% of all EVARS done in the United States. Balloon-expandable stent grafts require much less oversizing – less than 5% – to maintain their diameter post deployment, but they are rarely used. Indeed, the only commercially available balloon-expandable device in the United States is the TriVascular Ovation stent system, which seals the stent graft to the wall of the aorta via polyethylene glycol rather than by radial force.
Intriguingly, Italian investigators have reported that, in a multicenter series of 161 patients who underwent EVAR with the Ovation endograft, no AND occurred at CT scanning done after a minimum of 24 months of follow-up (J Vasc Surg. 2016;63[1]:8-15).
Previous studies of the implications of AND after EVAR have been limited to comparisons of early-generation devices, so Dr. Lee and his coinvestigators conducted a retrospective review of a prospective Stanford database that included 86 patients who underwent elective, uncomplicated infrarenal endovascular abdominal aortic aneurysm repairs using a variety of contemporary stent grafts. Eighty-six percent of patients experienced AND during a median radiologic follow-up of 21.9 months, with a mean 1.3-mm increase at 30 days and 3.3 mm at most recent follow-up. The degree of AND correlated with the amount of oversizing. However, AND didn’t vary significantly by device type, which included the Cook Zenith, Gore Excluder, Medtronic Endurant, and Endologix Powerlink self-expanding stent grafts (Ann Vasc Surg. 2017;43:115-20).
Aortic anatomy also plays a role in AND. Shorter necks with severe angulation have been found to pose a higher risk. Open repair, which entails much less AND than does EVAR, may make more sense in that challenging anatomic situation, according to Dr. Lee.
He reported current research funding from Cook, Gore, and Medtronic.
CHICAGO – Clinically significant aortic neck dilation occurs in one-quarter of patients after endovascular abdominal aortic aneurysm repair and is associated with sharply increased risk for type Ia endoleak, stent migration at the proximal seal zone, continued aneurysmal sack enlargement, and even aneurysm rupture, Jason T. Lee, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
He cited what he considers to be the best-quality systematic review of the literature regarding proximal neck dilation after endovascular aneurysm repair (EVAR), which was conducted by investigators at Paracelsus Medical University in Nuremberg, Germany. The data, he said, speak to the importance of trying to minimize the chances of aortic neck dilation (AND).
The review, which included 26 published studies through 2015 and nearly 10,000 EVAR patients, concluded that AND occurred in 24.6% of these patients. The investigators defined AND as more than 3 mm of dilation, which with an average neck diameter of about 30 mm in all comers, would represent a 10% aortic neck-diameter expansion. The incidence of the composite adverse outcome of type I endoleak, stent migration, and reintervention during a maximum of 9 years of follow-up was 29-fold greater in the AND group than in AND-free patients (J Endovasc Ther. 2017;24[1]:59-67).
Continuing controversy exists regarding the extent to which post-EVAR AND is a manifestation of the underlying aneurysmal process as opposed to an adverse effect caused by the outward radial force applied by the stent. That being said, there are several factors related to AND that are potentially within the vascular interventionalist’s control. Topping the list is aggressive oversizing of self-expanding stent grafts in an effort to obtain an excellent seal, according to Dr. Lee, a professor of surgery at Stanford (Calif.) University.
“The data from multiple series definitely suggests that more than 20% oversizing is correlated with a higher incidence of AND. So maybe the answer is oversizing by more like 10%-15%,” the vascular surgeon said.
Another factor contributing to AND is the overwhelming popularity of self-expanding aortic stent grafts, now utilized in 95% of all EVARS done in the United States. Balloon-expandable stent grafts require much less oversizing – less than 5% – to maintain their diameter post deployment, but they are rarely used. Indeed, the only commercially available balloon-expandable device in the United States is the TriVascular Ovation stent system, which seals the stent graft to the wall of the aorta via polyethylene glycol rather than by radial force.
Intriguingly, Italian investigators have reported that, in a multicenter series of 161 patients who underwent EVAR with the Ovation endograft, no AND occurred at CT scanning done after a minimum of 24 months of follow-up (J Vasc Surg. 2016;63[1]:8-15).
Previous studies of the implications of AND after EVAR have been limited to comparisons of early-generation devices, so Dr. Lee and his coinvestigators conducted a retrospective review of a prospective Stanford database that included 86 patients who underwent elective, uncomplicated infrarenal endovascular abdominal aortic aneurysm repairs using a variety of contemporary stent grafts. Eighty-six percent of patients experienced AND during a median radiologic follow-up of 21.9 months, with a mean 1.3-mm increase at 30 days and 3.3 mm at most recent follow-up. The degree of AND correlated with the amount of oversizing. However, AND didn’t vary significantly by device type, which included the Cook Zenith, Gore Excluder, Medtronic Endurant, and Endologix Powerlink self-expanding stent grafts (Ann Vasc Surg. 2017;43:115-20).
Aortic anatomy also plays a role in AND. Shorter necks with severe angulation have been found to pose a higher risk. Open repair, which entails much less AND than does EVAR, may make more sense in that challenging anatomic situation, according to Dr. Lee.
He reported current research funding from Cook, Gore, and Medtronic.
EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM
DMARDs improve vascular abnormalities in early RA
, Maya H. Buch, PhD, said at the annual meeting of the American College of Rheumatology.
She presented a study of 71 treatment-naive patients with recently diagnosed RA and no history of cardiovascular disease. Patients were randomized to either etanercept plus methotrexate or methotrexate with treat-to-target escalation to triple nonbiologic disease-modifying antirheumatic drug therapy by week 12. Patients in the latter group were switched to etanercept plus methotrexate at week 24 if at that point they had a Disease Activity Score 28 of 2.6 or more.
All participants underwent cardiovascular MRI at baseline and again after 1 and 2 years in order to measure change in aortic stiffness, the primary study endpoint chosen because it is clinically meaningful and can reliably and reproducibly be measured by MRI.
The study was designed to shed light on possible mechanisms for the epidemiologic observation that effective treatment with methotrexate and/or tumor necrosis factor (TNF) inhibitors curbs the excess risk of cardiovascular events that accompanies RA. The thinking is that abnormal aortic distensibility represents an early harbinger of the increased cardiovascular risk associated with this form of inflammatory arthritis, explained Dr. Buch, professor of rheumatology at the University of Leeds (England) and section head of clinical and translational rheumatology at the Leeds Institute of Rheumatic and Musculoskeletal Medicine.
The mean aortic distensibility at baseline, when the study population was treatment naive, was 2.99 x 10–3 mm Hg–1. This value is abnormally low when compared with values seen in healthy age- and sex-matched controls. After 1 year of treatment, however, mean aortic distensibility improved significantly to 3.59 x 10–3 mm Hg–1. This improvement was maintained at year 2, when the mean value was 3.55.
Interestingly, neither treatment response status or disease activity was associated with the improvement in aortic stiffness. However, in a prespecified exploratory comparison between the 20 responders to etanercept plus methotrexate and the 10 responders to first-line methotrexate who never received etanercept, the group on biologic therapy had a 16% greater improvement in aortic distensibility at 1 year.
“It’s not a statistically significant difference. The study wasn’t powered for that,” she said in an interview. “But these data suggest that an anti-TNF treatment strategy may confer additional benefit. Of course, that will need to be confirmed in a larger trial. And if it is confirmed, it would suggest a role for etanercept plus methotrexate in personalizing tailored therapy in early RA patients at particularly high cardiovascular risk.”
Dr. Buch reported receiving funding from Pfizer, Roche, UCB, AbbVie, Sanofi, Eli Lilly, and Sandoz, but reported having no financial conflicts of interest regarding this study, which was sponsored by the U.K. National Institute for Healthcare Research.
SOURCE: Buch MH et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L05.
, Maya H. Buch, PhD, said at the annual meeting of the American College of Rheumatology.
She presented a study of 71 treatment-naive patients with recently diagnosed RA and no history of cardiovascular disease. Patients were randomized to either etanercept plus methotrexate or methotrexate with treat-to-target escalation to triple nonbiologic disease-modifying antirheumatic drug therapy by week 12. Patients in the latter group were switched to etanercept plus methotrexate at week 24 if at that point they had a Disease Activity Score 28 of 2.6 or more.
All participants underwent cardiovascular MRI at baseline and again after 1 and 2 years in order to measure change in aortic stiffness, the primary study endpoint chosen because it is clinically meaningful and can reliably and reproducibly be measured by MRI.
The study was designed to shed light on possible mechanisms for the epidemiologic observation that effective treatment with methotrexate and/or tumor necrosis factor (TNF) inhibitors curbs the excess risk of cardiovascular events that accompanies RA. The thinking is that abnormal aortic distensibility represents an early harbinger of the increased cardiovascular risk associated with this form of inflammatory arthritis, explained Dr. Buch, professor of rheumatology at the University of Leeds (England) and section head of clinical and translational rheumatology at the Leeds Institute of Rheumatic and Musculoskeletal Medicine.
The mean aortic distensibility at baseline, when the study population was treatment naive, was 2.99 x 10–3 mm Hg–1. This value is abnormally low when compared with values seen in healthy age- and sex-matched controls. After 1 year of treatment, however, mean aortic distensibility improved significantly to 3.59 x 10–3 mm Hg–1. This improvement was maintained at year 2, when the mean value was 3.55.
Interestingly, neither treatment response status or disease activity was associated with the improvement in aortic stiffness. However, in a prespecified exploratory comparison between the 20 responders to etanercept plus methotrexate and the 10 responders to first-line methotrexate who never received etanercept, the group on biologic therapy had a 16% greater improvement in aortic distensibility at 1 year.
“It’s not a statistically significant difference. The study wasn’t powered for that,” she said in an interview. “But these data suggest that an anti-TNF treatment strategy may confer additional benefit. Of course, that will need to be confirmed in a larger trial. And if it is confirmed, it would suggest a role for etanercept plus methotrexate in personalizing tailored therapy in early RA patients at particularly high cardiovascular risk.”
Dr. Buch reported receiving funding from Pfizer, Roche, UCB, AbbVie, Sanofi, Eli Lilly, and Sandoz, but reported having no financial conflicts of interest regarding this study, which was sponsored by the U.K. National Institute for Healthcare Research.
SOURCE: Buch MH et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L05.
, Maya H. Buch, PhD, said at the annual meeting of the American College of Rheumatology.
She presented a study of 71 treatment-naive patients with recently diagnosed RA and no history of cardiovascular disease. Patients were randomized to either etanercept plus methotrexate or methotrexate with treat-to-target escalation to triple nonbiologic disease-modifying antirheumatic drug therapy by week 12. Patients in the latter group were switched to etanercept plus methotrexate at week 24 if at that point they had a Disease Activity Score 28 of 2.6 or more.
All participants underwent cardiovascular MRI at baseline and again after 1 and 2 years in order to measure change in aortic stiffness, the primary study endpoint chosen because it is clinically meaningful and can reliably and reproducibly be measured by MRI.
The study was designed to shed light on possible mechanisms for the epidemiologic observation that effective treatment with methotrexate and/or tumor necrosis factor (TNF) inhibitors curbs the excess risk of cardiovascular events that accompanies RA. The thinking is that abnormal aortic distensibility represents an early harbinger of the increased cardiovascular risk associated with this form of inflammatory arthritis, explained Dr. Buch, professor of rheumatology at the University of Leeds (England) and section head of clinical and translational rheumatology at the Leeds Institute of Rheumatic and Musculoskeletal Medicine.
The mean aortic distensibility at baseline, when the study population was treatment naive, was 2.99 x 10–3 mm Hg–1. This value is abnormally low when compared with values seen in healthy age- and sex-matched controls. After 1 year of treatment, however, mean aortic distensibility improved significantly to 3.59 x 10–3 mm Hg–1. This improvement was maintained at year 2, when the mean value was 3.55.
Interestingly, neither treatment response status or disease activity was associated with the improvement in aortic stiffness. However, in a prespecified exploratory comparison between the 20 responders to etanercept plus methotrexate and the 10 responders to first-line methotrexate who never received etanercept, the group on biologic therapy had a 16% greater improvement in aortic distensibility at 1 year.
“It’s not a statistically significant difference. The study wasn’t powered for that,” she said in an interview. “But these data suggest that an anti-TNF treatment strategy may confer additional benefit. Of course, that will need to be confirmed in a larger trial. And if it is confirmed, it would suggest a role for etanercept plus methotrexate in personalizing tailored therapy in early RA patients at particularly high cardiovascular risk.”
Dr. Buch reported receiving funding from Pfizer, Roche, UCB, AbbVie, Sanofi, Eli Lilly, and Sandoz, but reported having no financial conflicts of interest regarding this study, which was sponsored by the U.K. National Institute for Healthcare Research.
SOURCE: Buch MH et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L05.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Abnormal aortic stiffness is present in patients with newly diagnosed RA but improves with disease-modifying antirheumatic drug therapy.
Major finding: Mean aortic distensibility in patients with early RA improved from an abnormally low 2.99 x 10–3 mm Hg–1 prior to treatment to a more robust 3.59 x 10–3 mm Hg–1 after 1 year of disease-modifying antirheumatic drug therapy.
Study details: This study included 71 patients with newly diagnosed RA whose aortic stiffness was measured serially via cardiovascular MRI over a 2-year period.
Disclosures: The presenter reported receiving funding from Pfizer, Roche, UCB, AbbVie, Sanofi, Eli Lilly, and Sandoz, but reported having no financial conflicts of interest regarding this study, which was sponsored by the U.K. National Institute for Healthcare Research.
Source: Buch MH et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L05.
Open AAA repair mortality rates doubled for very-low-volume surgeons
NEW YORK – If New York State is representative, the risk of bad outcomes in patients undergoing open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA), including death in the case of OAR, is about double when performed by very low- versus higher-volume surgeons, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
“What should we do to fix the problem? We could require surgeons to track their outcomes in quality improvement registry,” suggested Jack L. Cronenwett, MD, professor of surgery, Geisel School of Medicine at Dartmouth, Hanover, N.H.
The outcomes were evaluated from inpatient data gathered from patients undergoing OAR or CEA in an all-payer database involving every hospital discharge in New York State. Surgeons were defined as very-low-volume for a given procedure if they averaged one or less per year, though the results held true if very-low-volume was defined as less than three cases per year, according to Dr. Cronenwett.
The database had outcomes on 8,781 OAR procedures and 68,896 CEA procedures performed from 2000 to 2014.
Of the 614 surgeons who performed one or more OARs over this period, 318 (51.8%) were defined as low-volume surgeons. Despite their substantial representation, they performed just 7.6% of the procedures.
When outcomes from procedures performed by very-low-volume surgeons were compared to those done by higher-volume surgeons, the mortality rates without adjustments were nearly double (6.7% vs. 3.5%; P less than .001). Procedures performed by low-volume surgeons were associated with far higher rates of sepsis or shock (5.7% vs. 3.7%; P = .008), and patients treated by low-volume surgeons were more likely to spend 9 or more days in the hospital (39.3% vs. 30.1%; P less than .001).
When fully adjusted for other variables, “low-volume surgeons had twofold higher odds [OR 2.09] of postoperative death,” Dr. Cronenwett reported.
Of the 1,071 surgeons who performed CEA over this period, 512 (47.8%) were low-volume. They performed 1.3% of the procedures.
Mortality and sepsis or shock following CEA were less than 1% in procedures performed by either low- or higher-volume surgeons without significant differences. However, procedures performed by low-volume surgeons were associated with a three-times higher rate of myocardial infarction (1.5% vs. 0.5%; P less than .001) and a 65% higher rate of stroke (3.5% vs. 2.1%; P = .003).
In addition, patients who underwent CEA performed by a low-volume surgeon had a significantly higher rate of 30-day readmission (11.5% vs. 8.5%; P = .002) and a significantly longer median length of stay (2 days vs. 1 day; P less than .001) than did those treated by a higher-volume surgeon.
Whether OAR or CEA, patients treated by a low-volume surgeon were more likely to have Medicaid coverage. The fact that procedures by low-volume surgeons were more likely to be performed in New York City than other areas of the state suggest that access to care was not a variable, according to Dr. Cronenwett.
Surgeon volume was calculated in this study by dividing the total number of OAR or CEA procedures performed by the number of years that the surgeon was in practice in New York State. Surgeons were classified as vascular surgeons if 75% or more of their surgical practice involved vascular procedures, cardiac surgeons if more than 20% of their surgical practice involved cardiac procedures, and general surgeons if they did not meet either of these criteria.
Of OAR procedures were done by a higher-volume surgeon, approximately 65% were by vascular specialists, 5% were by cardiac specialists, and the remaining were by general surgeons.
Of OAR procedures were done by a low-volume surgeon, approximately 25% were by vascular surgeons, 20% were by cardiac surgeons, and the remaining were by general surgeons. For CEA, there was a somewhat greater representation of general surgeons in both categories, but the patterns were similar.
Dr. Cronenwett argued that more rigorous steps should be taken to ensure that those with proven skills perform OAR and CEA and that open abdominal aortic aneurysm repair should be performed only by high-volume surgeons and hospitals. He suggested there are a variety of incentives or disincentives that could help, but he stressed the importance of tracking results and making them available to referring physicians and to patients.
“Some of the low-volume surgeons are probably not tracking their results so are not even aware of these bad outcomes,” he added.
Dr. Cronenwett reported that he had no relevant disclosures.
NEW YORK – If New York State is representative, the risk of bad outcomes in patients undergoing open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA), including death in the case of OAR, is about double when performed by very low- versus higher-volume surgeons, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
“What should we do to fix the problem? We could require surgeons to track their outcomes in quality improvement registry,” suggested Jack L. Cronenwett, MD, professor of surgery, Geisel School of Medicine at Dartmouth, Hanover, N.H.
The outcomes were evaluated from inpatient data gathered from patients undergoing OAR or CEA in an all-payer database involving every hospital discharge in New York State. Surgeons were defined as very-low-volume for a given procedure if they averaged one or less per year, though the results held true if very-low-volume was defined as less than three cases per year, according to Dr. Cronenwett.
The database had outcomes on 8,781 OAR procedures and 68,896 CEA procedures performed from 2000 to 2014.
Of the 614 surgeons who performed one or more OARs over this period, 318 (51.8%) were defined as low-volume surgeons. Despite their substantial representation, they performed just 7.6% of the procedures.
When outcomes from procedures performed by very-low-volume surgeons were compared to those done by higher-volume surgeons, the mortality rates without adjustments were nearly double (6.7% vs. 3.5%; P less than .001). Procedures performed by low-volume surgeons were associated with far higher rates of sepsis or shock (5.7% vs. 3.7%; P = .008), and patients treated by low-volume surgeons were more likely to spend 9 or more days in the hospital (39.3% vs. 30.1%; P less than .001).
When fully adjusted for other variables, “low-volume surgeons had twofold higher odds [OR 2.09] of postoperative death,” Dr. Cronenwett reported.
Of the 1,071 surgeons who performed CEA over this period, 512 (47.8%) were low-volume. They performed 1.3% of the procedures.
Mortality and sepsis or shock following CEA were less than 1% in procedures performed by either low- or higher-volume surgeons without significant differences. However, procedures performed by low-volume surgeons were associated with a three-times higher rate of myocardial infarction (1.5% vs. 0.5%; P less than .001) and a 65% higher rate of stroke (3.5% vs. 2.1%; P = .003).
In addition, patients who underwent CEA performed by a low-volume surgeon had a significantly higher rate of 30-day readmission (11.5% vs. 8.5%; P = .002) and a significantly longer median length of stay (2 days vs. 1 day; P less than .001) than did those treated by a higher-volume surgeon.
Whether OAR or CEA, patients treated by a low-volume surgeon were more likely to have Medicaid coverage. The fact that procedures by low-volume surgeons were more likely to be performed in New York City than other areas of the state suggest that access to care was not a variable, according to Dr. Cronenwett.
Surgeon volume was calculated in this study by dividing the total number of OAR or CEA procedures performed by the number of years that the surgeon was in practice in New York State. Surgeons were classified as vascular surgeons if 75% or more of their surgical practice involved vascular procedures, cardiac surgeons if more than 20% of their surgical practice involved cardiac procedures, and general surgeons if they did not meet either of these criteria.
Of OAR procedures were done by a higher-volume surgeon, approximately 65% were by vascular specialists, 5% were by cardiac specialists, and the remaining were by general surgeons.
Of OAR procedures were done by a low-volume surgeon, approximately 25% were by vascular surgeons, 20% were by cardiac surgeons, and the remaining were by general surgeons. For CEA, there was a somewhat greater representation of general surgeons in both categories, but the patterns were similar.
Dr. Cronenwett argued that more rigorous steps should be taken to ensure that those with proven skills perform OAR and CEA and that open abdominal aortic aneurysm repair should be performed only by high-volume surgeons and hospitals. He suggested there are a variety of incentives or disincentives that could help, but he stressed the importance of tracking results and making them available to referring physicians and to patients.
“Some of the low-volume surgeons are probably not tracking their results so are not even aware of these bad outcomes,” he added.
Dr. Cronenwett reported that he had no relevant disclosures.
NEW YORK – If New York State is representative, the risk of bad outcomes in patients undergoing open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA), including death in the case of OAR, is about double when performed by very low- versus higher-volume surgeons, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
“What should we do to fix the problem? We could require surgeons to track their outcomes in quality improvement registry,” suggested Jack L. Cronenwett, MD, professor of surgery, Geisel School of Medicine at Dartmouth, Hanover, N.H.
The outcomes were evaluated from inpatient data gathered from patients undergoing OAR or CEA in an all-payer database involving every hospital discharge in New York State. Surgeons were defined as very-low-volume for a given procedure if they averaged one or less per year, though the results held true if very-low-volume was defined as less than three cases per year, according to Dr. Cronenwett.
The database had outcomes on 8,781 OAR procedures and 68,896 CEA procedures performed from 2000 to 2014.
Of the 614 surgeons who performed one or more OARs over this period, 318 (51.8%) were defined as low-volume surgeons. Despite their substantial representation, they performed just 7.6% of the procedures.
When outcomes from procedures performed by very-low-volume surgeons were compared to those done by higher-volume surgeons, the mortality rates without adjustments were nearly double (6.7% vs. 3.5%; P less than .001). Procedures performed by low-volume surgeons were associated with far higher rates of sepsis or shock (5.7% vs. 3.7%; P = .008), and patients treated by low-volume surgeons were more likely to spend 9 or more days in the hospital (39.3% vs. 30.1%; P less than .001).
When fully adjusted for other variables, “low-volume surgeons had twofold higher odds [OR 2.09] of postoperative death,” Dr. Cronenwett reported.
Of the 1,071 surgeons who performed CEA over this period, 512 (47.8%) were low-volume. They performed 1.3% of the procedures.
Mortality and sepsis or shock following CEA were less than 1% in procedures performed by either low- or higher-volume surgeons without significant differences. However, procedures performed by low-volume surgeons were associated with a three-times higher rate of myocardial infarction (1.5% vs. 0.5%; P less than .001) and a 65% higher rate of stroke (3.5% vs. 2.1%; P = .003).
In addition, patients who underwent CEA performed by a low-volume surgeon had a significantly higher rate of 30-day readmission (11.5% vs. 8.5%; P = .002) and a significantly longer median length of stay (2 days vs. 1 day; P less than .001) than did those treated by a higher-volume surgeon.
Whether OAR or CEA, patients treated by a low-volume surgeon were more likely to have Medicaid coverage. The fact that procedures by low-volume surgeons were more likely to be performed in New York City than other areas of the state suggest that access to care was not a variable, according to Dr. Cronenwett.
Surgeon volume was calculated in this study by dividing the total number of OAR or CEA procedures performed by the number of years that the surgeon was in practice in New York State. Surgeons were classified as vascular surgeons if 75% or more of their surgical practice involved vascular procedures, cardiac surgeons if more than 20% of their surgical practice involved cardiac procedures, and general surgeons if they did not meet either of these criteria.
Of OAR procedures were done by a higher-volume surgeon, approximately 65% were by vascular specialists, 5% were by cardiac specialists, and the remaining were by general surgeons.
Of OAR procedures were done by a low-volume surgeon, approximately 25% were by vascular surgeons, 20% were by cardiac surgeons, and the remaining were by general surgeons. For CEA, there was a somewhat greater representation of general surgeons in both categories, but the patterns were similar.
Dr. Cronenwett argued that more rigorous steps should be taken to ensure that those with proven skills perform OAR and CEA and that open abdominal aortic aneurysm repair should be performed only by high-volume surgeons and hospitals. He suggested there are a variety of incentives or disincentives that could help, but he stressed the importance of tracking results and making them available to referring physicians and to patients.
“Some of the low-volume surgeons are probably not tracking their results so are not even aware of these bad outcomes,” he added.
Dr. Cronenwett reported that he had no relevant disclosures.
REPORTING FROM VEITHSYMPOSIUM
Key clinical point:
Major finding: In-hospital mortality is approximately double (OR 2.09; P less than .001) for very low-volume relative to high-volume surgeon.
Study details: Retrospective database review.
Disclosures: Dr. Cronenwett reports no conflicts of interest.
Source: Cronenwett JL et al. 2018; 45th VEITHsymposium.
At 10 years, reintervention rate for EVAR is 20%
NEW YORK – A clever strategy to evaluate long term outcomes in patients undergoing endovascular abdominal aortic aneurysm repair identified a 20% rate of reintervention, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation by Philip P. Goodney, MD.
In this video interview with Dr. Goodney, an associate professor of vascular surgery at Geisel School of Medicine at Dartmouth, Hanover, N.H., he explains how Medicare data were employed to track patients long term, even when they had moved to other hospital systems.
The main message from the long-term follow-up is that there is a persistent risk of recurrence and need for reintervention, according to Dr. Goodney. The hypothesis was that there would be an early risk of failure, followed by a diminishing need for reintervention over time, but this was not what was observed.Rather, the findings suggest that the rate of reinterventions was relatively steady over the course of follow-up, suggesting that patients should be informed of a persistent risk. However, Dr. Goodney reports that age was not a predictor of reintervention, so that older patients were at no greater risk.
NEW YORK – A clever strategy to evaluate long term outcomes in patients undergoing endovascular abdominal aortic aneurysm repair identified a 20% rate of reintervention, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation by Philip P. Goodney, MD.
In this video interview with Dr. Goodney, an associate professor of vascular surgery at Geisel School of Medicine at Dartmouth, Hanover, N.H., he explains how Medicare data were employed to track patients long term, even when they had moved to other hospital systems.
The main message from the long-term follow-up is that there is a persistent risk of recurrence and need for reintervention, according to Dr. Goodney. The hypothesis was that there would be an early risk of failure, followed by a diminishing need for reintervention over time, but this was not what was observed.Rather, the findings suggest that the rate of reinterventions was relatively steady over the course of follow-up, suggesting that patients should be informed of a persistent risk. However, Dr. Goodney reports that age was not a predictor of reintervention, so that older patients were at no greater risk.
NEW YORK – A clever strategy to evaluate long term outcomes in patients undergoing endovascular abdominal aortic aneurysm repair identified a 20% rate of reintervention, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation by Philip P. Goodney, MD.
In this video interview with Dr. Goodney, an associate professor of vascular surgery at Geisel School of Medicine at Dartmouth, Hanover, N.H., he explains how Medicare data were employed to track patients long term, even when they had moved to other hospital systems.
The main message from the long-term follow-up is that there is a persistent risk of recurrence and need for reintervention, according to Dr. Goodney. The hypothesis was that there would be an early risk of failure, followed by a diminishing need for reintervention over time, but this was not what was observed.Rather, the findings suggest that the rate of reinterventions was relatively steady over the course of follow-up, suggesting that patients should be informed of a persistent risk. However, Dr. Goodney reports that age was not a predictor of reintervention, so that older patients were at no greater risk.
FROM 2018 VEITH SYMPOSIUM
Snorkel/chimney repair of aortic aneurysms is still effective after 4 years
NEW YORK – With a median follow-up of almost 4 years in more than 200 patients, the snorkel/chimney technique of endovascular repair of complex abdominal aortic aneurysms continues to generate very good results, according data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
In a video interview with Jason T. Lee, MD, professor of vascular surgery, Stanford (Calif.) University, who presented the long-term results, he explains why these findings are important.
After several single-center studies associated the snorkel/chimney technique with good rates of patency and durability, the PERICLES Registry was created almost 10 years ago to test whether these data could be reproduced in the real world.The data presented by Dr. Lee involved outcomes in 244 patients who were followed for at least 2.5 years. The median follow-up is 47 months.
The results overall confirm that this is a viable technique, according to Dr. Lee who noted very little diminution of patency rates in this long-term cohort relative to the previously published follow-up of 17.1 months.
He acknowledged that the snorkel/chimney repair is not free of potential complications, particularly gutter endovascular leaks, but he recounted that at least some resolve over time. Moreover, he suggests that several strategies are being pursued that appear promising for avoiding this risk.
Most importantly, the registry, which captured the experience at 13 centers in the United States and Europe, shows outcomes that are similar to those reported at centers where the techniques were developed and championed.
NEW YORK – With a median follow-up of almost 4 years in more than 200 patients, the snorkel/chimney technique of endovascular repair of complex abdominal aortic aneurysms continues to generate very good results, according data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
In a video interview with Jason T. Lee, MD, professor of vascular surgery, Stanford (Calif.) University, who presented the long-term results, he explains why these findings are important.
After several single-center studies associated the snorkel/chimney technique with good rates of patency and durability, the PERICLES Registry was created almost 10 years ago to test whether these data could be reproduced in the real world.The data presented by Dr. Lee involved outcomes in 244 patients who were followed for at least 2.5 years. The median follow-up is 47 months.
The results overall confirm that this is a viable technique, according to Dr. Lee who noted very little diminution of patency rates in this long-term cohort relative to the previously published follow-up of 17.1 months.
He acknowledged that the snorkel/chimney repair is not free of potential complications, particularly gutter endovascular leaks, but he recounted that at least some resolve over time. Moreover, he suggests that several strategies are being pursued that appear promising for avoiding this risk.
Most importantly, the registry, which captured the experience at 13 centers in the United States and Europe, shows outcomes that are similar to those reported at centers where the techniques were developed and championed.
NEW YORK – With a median follow-up of almost 4 years in more than 200 patients, the snorkel/chimney technique of endovascular repair of complex abdominal aortic aneurysms continues to generate very good results, according data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
In a video interview with Jason T. Lee, MD, professor of vascular surgery, Stanford (Calif.) University, who presented the long-term results, he explains why these findings are important.
After several single-center studies associated the snorkel/chimney technique with good rates of patency and durability, the PERICLES Registry was created almost 10 years ago to test whether these data could be reproduced in the real world.The data presented by Dr. Lee involved outcomes in 244 patients who were followed for at least 2.5 years. The median follow-up is 47 months.
The results overall confirm that this is a viable technique, according to Dr. Lee who noted very little diminution of patency rates in this long-term cohort relative to the previously published follow-up of 17.1 months.
He acknowledged that the snorkel/chimney repair is not free of potential complications, particularly gutter endovascular leaks, but he recounted that at least some resolve over time. Moreover, he suggests that several strategies are being pursued that appear promising for avoiding this risk.
Most importantly, the registry, which captured the experience at 13 centers in the United States and Europe, shows outcomes that are similar to those reported at centers where the techniques were developed and championed.
FROM 2018 VEITH SYMPOSIUM
A bovine arch predicts worse outcomes with type B aortic dissections
NEW YORK – The presence of a bovine arch predicts higher mortality in patients with a type B aortic dissection (TBAD), according to a study presented by Jan S. Brunkwall, MD, at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
The bovine arch is a congenital interruption in the evolution of the arch, and is a misnomer because it does not actually reflect the arch branching pattern found in cattle. It represents the most common variation of the aortic arch, with a prevalence of 1%-41%, depending on the literature, according to a study published by Dr. Brunkwall, chairman of the department of vascular and endovascular surgery at the University of Cologne (Germany), and his colleagues (Eur J Vasc Endovasc Surg. 2018; 55:385-391).
In order to assess the effect of the bovine arch on survival, Dr. Brunkwall and his colleagues performed a retrospective cohort analysis of patients with TBAD admitted at two centers. CT angiograms (CTAs) of patients referred because of aortic dissection were also reevaluated with regard to the presence of a bovine arch.
A total of 154 patients with TBAD and 168 with type A aortic dissection were assessed, and 110 oncologic patients who had undergone a chest CTA for disease staging during the study period acted as a control group.
There was an overall prevalence of 17.6% for bovine arch variants, with no statistical difference in prevalence between patients with a dissection and those in the control group, or between patients with a type A or type B dissection. However, mortality was 34.5% in patients with TBAD who had a bovine arch versus 16% in patients without a bovine arch. This was a significant difference (P =.04), according to Dr. Brunkwall.
Multivariate analysis showed that the presence of a bovine arch with TBAD was an independent predictor of mortality. “The reason for the high mortality cannot be explained by our data,” said Dr. Brunkwall, “but there has been a suggestion that the shear stress is different and higher in patients with a bovine arch leading to a stiffer aorta and more endothelial damage.”
Dr. Brunkwall reported that he had no disclosures.
NEW YORK – The presence of a bovine arch predicts higher mortality in patients with a type B aortic dissection (TBAD), according to a study presented by Jan S. Brunkwall, MD, at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
The bovine arch is a congenital interruption in the evolution of the arch, and is a misnomer because it does not actually reflect the arch branching pattern found in cattle. It represents the most common variation of the aortic arch, with a prevalence of 1%-41%, depending on the literature, according to a study published by Dr. Brunkwall, chairman of the department of vascular and endovascular surgery at the University of Cologne (Germany), and his colleagues (Eur J Vasc Endovasc Surg. 2018; 55:385-391).
In order to assess the effect of the bovine arch on survival, Dr. Brunkwall and his colleagues performed a retrospective cohort analysis of patients with TBAD admitted at two centers. CT angiograms (CTAs) of patients referred because of aortic dissection were also reevaluated with regard to the presence of a bovine arch.
A total of 154 patients with TBAD and 168 with type A aortic dissection were assessed, and 110 oncologic patients who had undergone a chest CTA for disease staging during the study period acted as a control group.
There was an overall prevalence of 17.6% for bovine arch variants, with no statistical difference in prevalence between patients with a dissection and those in the control group, or between patients with a type A or type B dissection. However, mortality was 34.5% in patients with TBAD who had a bovine arch versus 16% in patients without a bovine arch. This was a significant difference (P =.04), according to Dr. Brunkwall.
Multivariate analysis showed that the presence of a bovine arch with TBAD was an independent predictor of mortality. “The reason for the high mortality cannot be explained by our data,” said Dr. Brunkwall, “but there has been a suggestion that the shear stress is different and higher in patients with a bovine arch leading to a stiffer aorta and more endothelial damage.”
Dr. Brunkwall reported that he had no disclosures.
NEW YORK – The presence of a bovine arch predicts higher mortality in patients with a type B aortic dissection (TBAD), according to a study presented by Jan S. Brunkwall, MD, at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.
The bovine arch is a congenital interruption in the evolution of the arch, and is a misnomer because it does not actually reflect the arch branching pattern found in cattle. It represents the most common variation of the aortic arch, with a prevalence of 1%-41%, depending on the literature, according to a study published by Dr. Brunkwall, chairman of the department of vascular and endovascular surgery at the University of Cologne (Germany), and his colleagues (Eur J Vasc Endovasc Surg. 2018; 55:385-391).
In order to assess the effect of the bovine arch on survival, Dr. Brunkwall and his colleagues performed a retrospective cohort analysis of patients with TBAD admitted at two centers. CT angiograms (CTAs) of patients referred because of aortic dissection were also reevaluated with regard to the presence of a bovine arch.
A total of 154 patients with TBAD and 168 with type A aortic dissection were assessed, and 110 oncologic patients who had undergone a chest CTA for disease staging during the study period acted as a control group.
There was an overall prevalence of 17.6% for bovine arch variants, with no statistical difference in prevalence between patients with a dissection and those in the control group, or between patients with a type A or type B dissection. However, mortality was 34.5% in patients with TBAD who had a bovine arch versus 16% in patients without a bovine arch. This was a significant difference (P =.04), according to Dr. Brunkwall.
Multivariate analysis showed that the presence of a bovine arch with TBAD was an independent predictor of mortality. “The reason for the high mortality cannot be explained by our data,” said Dr. Brunkwall, “but there has been a suggestion that the shear stress is different and higher in patients with a bovine arch leading to a stiffer aorta and more endothelial damage.”
Dr. Brunkwall reported that he had no disclosures.
REPORTING FROM VEITHSYMPOSIUM
Vascular ultrasound reasonable for first-line imaging of large-vessel GCA
CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.
The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.
Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.
Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.
“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”
The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.
Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.
Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.
The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.
Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.
Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.
“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”
New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.
Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.
Indeed, the current findings support its use in this setting, she said.
“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.
Dr. Nielsen disclosed a relationship with Roche.
SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.
CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.
The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.
Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.
Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.
“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”
The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.
Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.
Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.
The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.
Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.
Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.
“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”
New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.
Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.
Indeed, the current findings support its use in this setting, she said.
“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.
Dr. Nielsen disclosed a relationship with Roche.
SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.
CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.
The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.
Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.
Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.
“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”
The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.
Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.
Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.
The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.
Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.
Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.
“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”
New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.
Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.
Indeed, the current findings support its use in this setting, she said.
“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.
Dr. Nielsen disclosed a relationship with Roche.
SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Vascular ultrasound is reasonable for first-line maging of suspected LV-GCA.
Major finding: Vascular ultrasound had 100% specificity and 80% sensitivity.
Study details: A prospective study of 86 patients.
Disclosures: Dr. Nielsen disclosed a relationship with Roche.
Source: Nielsen BD et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.