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Ultrasound expedites pediatric emergency evaluations
LAKE BUENA VISTA, FLA. – Ultrasound expedites clinical decision making and often dictates the next step to pursue when managing children in the emergency department.
"It makes sense to use ultrasound for pediatric patients, but there’s been a delay in picking up this idea. Only now is (the use of bedside ultrasonography) becoming more prevalent in pediatric emergency medicine, Dr. Stephanie J. Doniger said at a meeting sponsored by the American College of Emergency Physicians and the American Academy of Pediatrics.
"Among the advantages is that we really never have to perform sedation, and the absolutely most important thing, we don’t need to use ionizing radiation," said Dr. Doniger, director of emergency ultrasound at Children’s Hospital and Research Center, Oakland, Calif.
Still, she said, there are no clear guidelines for ultrasonography’s use in pediatric emergencies. No one body oversees the quality in training or in outcomes. In 2009, ACEP updated its guidelines on bedside ultrasound in the emergency department. The group gave a nod to pediatric use, calling ultrasonography "an ideal diagnostic tool for children ... As in adult patients, emergency ultrasound in children can be life saving, time saving, [can] increase procedural efficiency, and [can] maximize patient safety."
The document says ultrasound is particularly useful in performing the FAST exam, and for bladder evaluations prior to instilling a catheter in infants. Dr. Doniger noted a number of other applications as well.
Ultrasonography is valuable for assessing dehydration by providing a look at the inferior vena cava. "We’re looking here for collapsibility during inspiration. Collapsibility of more than 50% correlates with dehydration."
Appendicitis is tough to image, radiographs are unreliable, and "CTs aren’t great, but we do them if we have to." But ultrasound provides a very good look into what lies beneath, and is one more way to reduce a child’s cumulative radiation dose.
A 2008 study found that a 5-minute bedside ultrasound had a sensitivity of 65% and a specificity of 90% for appendicitis. The positive predictive value was 84%, and the negative predictive value, 76%.
"That might not sound great, but it is a good result to rule in disease. If you have a high suspicion of appendicitis, then use it; if a low suspicion, then don’t."
When looking for an infected appendix, start at the point of maximal tenderness and move to the right while the child is in an oblique position. "It helps if you prop up the hip with some towels," Dr. Doniger said. "The bowel will move away and you’ll have a better view when you compress."
Look for a noncompressible tubular structure with a diameter greater than 6 mm.
The probe can also help find intussusception – a condition that x-rays identify 40%-90% of the time. The ultrasound image of intussusception is target- or doughnut-shaped – a figure formed when the bowel retracts back into itself. A study found that even beginning sonographers can identify this classic sign. Their exams had a sensitivity of 85%, a specificity of 97%, a positive predictive value of 85%, and a negative predictive value of 97%.
Even something that seems innocuous on the surface – like a splinter – will give up its secrets under the ultrasound probe. Foreign bodies may or may not show up on an x-ray, but they are obviously hypoechoic on ultrasound, she said.
Dr. Doniger presented the case of a 13-year-old who thought he got a splinter under his fingernail, but wasn’t sure. He came to the emergency department after his finger became stiff and a little painful. Ultrasound identified the culprit as splinter of wood that was more than 1 inch long.
Guiding the needle during an evaluation for painful hips for effusion is another great use for ultrasound, she said. A 2009 study determined that, compared with ultrasound alone; sonography-guided arthrocentesis for symptomatic hips had 90% sensitivity and 100% specificity, with a 100% positive predictive value and a 92% negative predictive value.
Ultrasound also provides valuable assistance in identifying the landmarks for successful needle placement when performing a spinal tap. A 2007 study equally randomized 46 children to finding the landmarks by palpation or with ultrasound. There were six failed attempts in the palpation group and one in the ultrasound group. Ultrasound was particularly helpful in obese children; four of seven palpation placements failed, compared with no failures in the ultrasound group.
None of the authors declared any financial relationships. The study was funded by the Lynn Sage Cancer Research Foundation, the Avon Foundation, and a private contribution.
LAKE BUENA VISTA, FLA. – Ultrasound expedites clinical decision making and often dictates the next step to pursue when managing children in the emergency department.
"It makes sense to use ultrasound for pediatric patients, but there’s been a delay in picking up this idea. Only now is (the use of bedside ultrasonography) becoming more prevalent in pediatric emergency medicine, Dr. Stephanie J. Doniger said at a meeting sponsored by the American College of Emergency Physicians and the American Academy of Pediatrics.
"Among the advantages is that we really never have to perform sedation, and the absolutely most important thing, we don’t need to use ionizing radiation," said Dr. Doniger, director of emergency ultrasound at Children’s Hospital and Research Center, Oakland, Calif.
Still, she said, there are no clear guidelines for ultrasonography’s use in pediatric emergencies. No one body oversees the quality in training or in outcomes. In 2009, ACEP updated its guidelines on bedside ultrasound in the emergency department. The group gave a nod to pediatric use, calling ultrasonography "an ideal diagnostic tool for children ... As in adult patients, emergency ultrasound in children can be life saving, time saving, [can] increase procedural efficiency, and [can] maximize patient safety."
The document says ultrasound is particularly useful in performing the FAST exam, and for bladder evaluations prior to instilling a catheter in infants. Dr. Doniger noted a number of other applications as well.
Ultrasonography is valuable for assessing dehydration by providing a look at the inferior vena cava. "We’re looking here for collapsibility during inspiration. Collapsibility of more than 50% correlates with dehydration."
Appendicitis is tough to image, radiographs are unreliable, and "CTs aren’t great, but we do them if we have to." But ultrasound provides a very good look into what lies beneath, and is one more way to reduce a child’s cumulative radiation dose.
A 2008 study found that a 5-minute bedside ultrasound had a sensitivity of 65% and a specificity of 90% for appendicitis. The positive predictive value was 84%, and the negative predictive value, 76%.
"That might not sound great, but it is a good result to rule in disease. If you have a high suspicion of appendicitis, then use it; if a low suspicion, then don’t."
When looking for an infected appendix, start at the point of maximal tenderness and move to the right while the child is in an oblique position. "It helps if you prop up the hip with some towels," Dr. Doniger said. "The bowel will move away and you’ll have a better view when you compress."
Look for a noncompressible tubular structure with a diameter greater than 6 mm.
The probe can also help find intussusception – a condition that x-rays identify 40%-90% of the time. The ultrasound image of intussusception is target- or doughnut-shaped – a figure formed when the bowel retracts back into itself. A study found that even beginning sonographers can identify this classic sign. Their exams had a sensitivity of 85%, a specificity of 97%, a positive predictive value of 85%, and a negative predictive value of 97%.
Even something that seems innocuous on the surface – like a splinter – will give up its secrets under the ultrasound probe. Foreign bodies may or may not show up on an x-ray, but they are obviously hypoechoic on ultrasound, she said.
Dr. Doniger presented the case of a 13-year-old who thought he got a splinter under his fingernail, but wasn’t sure. He came to the emergency department after his finger became stiff and a little painful. Ultrasound identified the culprit as splinter of wood that was more than 1 inch long.
Guiding the needle during an evaluation for painful hips for effusion is another great use for ultrasound, she said. A 2009 study determined that, compared with ultrasound alone; sonography-guided arthrocentesis for symptomatic hips had 90% sensitivity and 100% specificity, with a 100% positive predictive value and a 92% negative predictive value.
Ultrasound also provides valuable assistance in identifying the landmarks for successful needle placement when performing a spinal tap. A 2007 study equally randomized 46 children to finding the landmarks by palpation or with ultrasound. There were six failed attempts in the palpation group and one in the ultrasound group. Ultrasound was particularly helpful in obese children; four of seven palpation placements failed, compared with no failures in the ultrasound group.
None of the authors declared any financial relationships. The study was funded by the Lynn Sage Cancer Research Foundation, the Avon Foundation, and a private contribution.
LAKE BUENA VISTA, FLA. – Ultrasound expedites clinical decision making and often dictates the next step to pursue when managing children in the emergency department.
"It makes sense to use ultrasound for pediatric patients, but there’s been a delay in picking up this idea. Only now is (the use of bedside ultrasonography) becoming more prevalent in pediatric emergency medicine, Dr. Stephanie J. Doniger said at a meeting sponsored by the American College of Emergency Physicians and the American Academy of Pediatrics.
"Among the advantages is that we really never have to perform sedation, and the absolutely most important thing, we don’t need to use ionizing radiation," said Dr. Doniger, director of emergency ultrasound at Children’s Hospital and Research Center, Oakland, Calif.
Still, she said, there are no clear guidelines for ultrasonography’s use in pediatric emergencies. No one body oversees the quality in training or in outcomes. In 2009, ACEP updated its guidelines on bedside ultrasound in the emergency department. The group gave a nod to pediatric use, calling ultrasonography "an ideal diagnostic tool for children ... As in adult patients, emergency ultrasound in children can be life saving, time saving, [can] increase procedural efficiency, and [can] maximize patient safety."
The document says ultrasound is particularly useful in performing the FAST exam, and for bladder evaluations prior to instilling a catheter in infants. Dr. Doniger noted a number of other applications as well.
Ultrasonography is valuable for assessing dehydration by providing a look at the inferior vena cava. "We’re looking here for collapsibility during inspiration. Collapsibility of more than 50% correlates with dehydration."
Appendicitis is tough to image, radiographs are unreliable, and "CTs aren’t great, but we do them if we have to." But ultrasound provides a very good look into what lies beneath, and is one more way to reduce a child’s cumulative radiation dose.
A 2008 study found that a 5-minute bedside ultrasound had a sensitivity of 65% and a specificity of 90% for appendicitis. The positive predictive value was 84%, and the negative predictive value, 76%.
"That might not sound great, but it is a good result to rule in disease. If you have a high suspicion of appendicitis, then use it; if a low suspicion, then don’t."
When looking for an infected appendix, start at the point of maximal tenderness and move to the right while the child is in an oblique position. "It helps if you prop up the hip with some towels," Dr. Doniger said. "The bowel will move away and you’ll have a better view when you compress."
Look for a noncompressible tubular structure with a diameter greater than 6 mm.
The probe can also help find intussusception – a condition that x-rays identify 40%-90% of the time. The ultrasound image of intussusception is target- or doughnut-shaped – a figure formed when the bowel retracts back into itself. A study found that even beginning sonographers can identify this classic sign. Their exams had a sensitivity of 85%, a specificity of 97%, a positive predictive value of 85%, and a negative predictive value of 97%.
Even something that seems innocuous on the surface – like a splinter – will give up its secrets under the ultrasound probe. Foreign bodies may or may not show up on an x-ray, but they are obviously hypoechoic on ultrasound, she said.
Dr. Doniger presented the case of a 13-year-old who thought he got a splinter under his fingernail, but wasn’t sure. He came to the emergency department after his finger became stiff and a little painful. Ultrasound identified the culprit as splinter of wood that was more than 1 inch long.
Guiding the needle during an evaluation for painful hips for effusion is another great use for ultrasound, she said. A 2009 study determined that, compared with ultrasound alone; sonography-guided arthrocentesis for symptomatic hips had 90% sensitivity and 100% specificity, with a 100% positive predictive value and a 92% negative predictive value.
Ultrasound also provides valuable assistance in identifying the landmarks for successful needle placement when performing a spinal tap. A 2007 study equally randomized 46 children to finding the landmarks by palpation or with ultrasound. There were six failed attempts in the palpation group and one in the ultrasound group. Ultrasound was particularly helpful in obese children; four of seven palpation placements failed, compared with no failures in the ultrasound group.
None of the authors declared any financial relationships. The study was funded by the Lynn Sage Cancer Research Foundation, the Avon Foundation, and a private contribution.
EXPERT ANALYSIS AT THE ADVANCED PEDIATRIC EMERGENCY MEDICINE ASSEMBLY
In the Hips, Increasing Pain and Decreasing Range of Motion
Not all joint pain is arthritis
A 47-year-old man who had been diagnosed with rheumatoid arthritis 5 years previously was referred to us for management of bilateral pleural effusions.
At the time of his diagnosis, his symptoms included pain and swelling of both wrists and the metacarpal joints of both hands. His serum C-reactive protein level had been elevated at that time, but he had no detectable rheumatoid factor. Findings on magnetic resonance imaging of the hand were very suggestive of rheumatoid arthritis (Figure 1).
He had been started on the anti-tumor necrosis factor agent etanercept but his symptoms improved only slightly, and therefore a glucocorticoid had been added.
Two years later, he developed abdominal pain, for which he underwent cholecystectomy. However, he continued to have chronic, generalized abdominal pain, and over the next 4 years he lost 25 lb. Upper endoscopy showed no mucosal changes, and multiple random biopsy samples were obtained for histologic evaluation (FIGURE 2) as part of his workup for chronic abdominal pain.
Q: What is the diagnosis?
A: As shown in Figure 2, staining of duodenal specimens showed intact villous architecture, with focal expansion of the lamina propria by “foamy” macrophages, rare plasma cells, and eosinophils, a key feature of Whipple disease. Periodic acid-Schiff staining showed numerous bacilli within the macrophages, thus confirming the diagnosis of Whipple disease. The diagnosis was also confirmed by polymerase chain reaction testing. Staining for acid-fast bacilli was negative.
WHEN TO CONSIDER WHIPPLE DISEASE
Whipple disease is a rare systemic disease with a very low incidence rate worldwide. Thus, its prevalence is difficult to estimate accurately. It is caused by a gram-positive bacterium, Tropheryma whippelii.1,2 The typical clinical manifestations are diarrhea, abdominal pain, weight loss, and fever. In most patients, these are often preceded by articular symptoms,3 as in our patient, who had articular symptoms for 5 years before he was diagnosed with Whipple disease.
Interestingly, our patient also had pleural effusion, which is uncommon in Whipple disease.4
The pathogenesis of Whipple disease is thought to be related to bacterial replication within macrophages, which leads to a systemic immune response and tissue infiltration by the organism.5 Histologic evaluation is the most common way to confirm the diagnosis.
As our patient’s disease course illustrates, Whipple disease should be part of the differential diagnosis of arthritis, as antibiotic therapy alone leads to a dramatic clinical response.
Our patient was started on a 2-week course of intravenous ceftriaxone followed by oral sulfamethoxazole and trimethoprim, and his abdominal and articular symptoms completely resolved within 4 weeks.
- Dutly F, Altwegg M. Whipple’s disease and ‘Tropheryma whippelii.’ Clin Microbiol Rev 2001; 14:561–583.
- Raoult D, Birg ML, La Scola B, et al. Cultivation of the bacillus of Whipple’s disease. N Engl J Med 2000; 342:620–625.
- Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple’s disease. N Engl J Med 1992; 327:293–301.
- Durand DV, Lecomte C, Cathébras P, Rousset H, Godeau P. Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple disease. Société Nationale Française de Médecine Interne. Medicine (Baltimore) 1997; 76:170–184.
- Dobbins WO, Ruffin JM. A light- and electron-microscopic study of bacterial invasion in Whipple’s disease. Am J Pathol 1967; 51:225–242.
A 47-year-old man who had been diagnosed with rheumatoid arthritis 5 years previously was referred to us for management of bilateral pleural effusions.
At the time of his diagnosis, his symptoms included pain and swelling of both wrists and the metacarpal joints of both hands. His serum C-reactive protein level had been elevated at that time, but he had no detectable rheumatoid factor. Findings on magnetic resonance imaging of the hand were very suggestive of rheumatoid arthritis (Figure 1).
He had been started on the anti-tumor necrosis factor agent etanercept but his symptoms improved only slightly, and therefore a glucocorticoid had been added.
Two years later, he developed abdominal pain, for which he underwent cholecystectomy. However, he continued to have chronic, generalized abdominal pain, and over the next 4 years he lost 25 lb. Upper endoscopy showed no mucosal changes, and multiple random biopsy samples were obtained for histologic evaluation (FIGURE 2) as part of his workup for chronic abdominal pain.
Q: What is the diagnosis?
A: As shown in Figure 2, staining of duodenal specimens showed intact villous architecture, with focal expansion of the lamina propria by “foamy” macrophages, rare plasma cells, and eosinophils, a key feature of Whipple disease. Periodic acid-Schiff staining showed numerous bacilli within the macrophages, thus confirming the diagnosis of Whipple disease. The diagnosis was also confirmed by polymerase chain reaction testing. Staining for acid-fast bacilli was negative.
WHEN TO CONSIDER WHIPPLE DISEASE
Whipple disease is a rare systemic disease with a very low incidence rate worldwide. Thus, its prevalence is difficult to estimate accurately. It is caused by a gram-positive bacterium, Tropheryma whippelii.1,2 The typical clinical manifestations are diarrhea, abdominal pain, weight loss, and fever. In most patients, these are often preceded by articular symptoms,3 as in our patient, who had articular symptoms for 5 years before he was diagnosed with Whipple disease.
Interestingly, our patient also had pleural effusion, which is uncommon in Whipple disease.4
The pathogenesis of Whipple disease is thought to be related to bacterial replication within macrophages, which leads to a systemic immune response and tissue infiltration by the organism.5 Histologic evaluation is the most common way to confirm the diagnosis.
As our patient’s disease course illustrates, Whipple disease should be part of the differential diagnosis of arthritis, as antibiotic therapy alone leads to a dramatic clinical response.
Our patient was started on a 2-week course of intravenous ceftriaxone followed by oral sulfamethoxazole and trimethoprim, and his abdominal and articular symptoms completely resolved within 4 weeks.
A 47-year-old man who had been diagnosed with rheumatoid arthritis 5 years previously was referred to us for management of bilateral pleural effusions.
At the time of his diagnosis, his symptoms included pain and swelling of both wrists and the metacarpal joints of both hands. His serum C-reactive protein level had been elevated at that time, but he had no detectable rheumatoid factor. Findings on magnetic resonance imaging of the hand were very suggestive of rheumatoid arthritis (Figure 1).
He had been started on the anti-tumor necrosis factor agent etanercept but his symptoms improved only slightly, and therefore a glucocorticoid had been added.
Two years later, he developed abdominal pain, for which he underwent cholecystectomy. However, he continued to have chronic, generalized abdominal pain, and over the next 4 years he lost 25 lb. Upper endoscopy showed no mucosal changes, and multiple random biopsy samples were obtained for histologic evaluation (FIGURE 2) as part of his workup for chronic abdominal pain.
Q: What is the diagnosis?
A: As shown in Figure 2, staining of duodenal specimens showed intact villous architecture, with focal expansion of the lamina propria by “foamy” macrophages, rare plasma cells, and eosinophils, a key feature of Whipple disease. Periodic acid-Schiff staining showed numerous bacilli within the macrophages, thus confirming the diagnosis of Whipple disease. The diagnosis was also confirmed by polymerase chain reaction testing. Staining for acid-fast bacilli was negative.
WHEN TO CONSIDER WHIPPLE DISEASE
Whipple disease is a rare systemic disease with a very low incidence rate worldwide. Thus, its prevalence is difficult to estimate accurately. It is caused by a gram-positive bacterium, Tropheryma whippelii.1,2 The typical clinical manifestations are diarrhea, abdominal pain, weight loss, and fever. In most patients, these are often preceded by articular symptoms,3 as in our patient, who had articular symptoms for 5 years before he was diagnosed with Whipple disease.
Interestingly, our patient also had pleural effusion, which is uncommon in Whipple disease.4
The pathogenesis of Whipple disease is thought to be related to bacterial replication within macrophages, which leads to a systemic immune response and tissue infiltration by the organism.5 Histologic evaluation is the most common way to confirm the diagnosis.
As our patient’s disease course illustrates, Whipple disease should be part of the differential diagnosis of arthritis, as antibiotic therapy alone leads to a dramatic clinical response.
Our patient was started on a 2-week course of intravenous ceftriaxone followed by oral sulfamethoxazole and trimethoprim, and his abdominal and articular symptoms completely resolved within 4 weeks.
- Dutly F, Altwegg M. Whipple’s disease and ‘Tropheryma whippelii.’ Clin Microbiol Rev 2001; 14:561–583.
- Raoult D, Birg ML, La Scola B, et al. Cultivation of the bacillus of Whipple’s disease. N Engl J Med 2000; 342:620–625.
- Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple’s disease. N Engl J Med 1992; 327:293–301.
- Durand DV, Lecomte C, Cathébras P, Rousset H, Godeau P. Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple disease. Société Nationale Française de Médecine Interne. Medicine (Baltimore) 1997; 76:170–184.
- Dobbins WO, Ruffin JM. A light- and electron-microscopic study of bacterial invasion in Whipple’s disease. Am J Pathol 1967; 51:225–242.
- Dutly F, Altwegg M. Whipple’s disease and ‘Tropheryma whippelii.’ Clin Microbiol Rev 2001; 14:561–583.
- Raoult D, Birg ML, La Scola B, et al. Cultivation of the bacillus of Whipple’s disease. N Engl J Med 2000; 342:620–625.
- Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple’s disease. N Engl J Med 1992; 327:293–301.
- Durand DV, Lecomte C, Cathébras P, Rousset H, Godeau P. Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple disease. Société Nationale Française de Médecine Interne. Medicine (Baltimore) 1997; 76:170–184.
- Dobbins WO, Ruffin JM. A light- and electron-microscopic study of bacterial invasion in Whipple’s disease. Am J Pathol 1967; 51:225–242.
RA patients have increased aortic inflammation
NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.
"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.
It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.
Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.
RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.
The results of the study were presented previously at the 2012 ACR Annual Meeting.
Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.
NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.
"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.
It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.
Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.
RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.
The results of the study were presented previously at the 2012 ACR Annual Meeting.
Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.
NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.
"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.
It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.
Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.
RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.
The results of the study were presented previously at the 2012 ACR Annual Meeting.
Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.
AT THE NYU SEMINAR IN ADVANCED RHEUMATOLOGY
Implications of a prominent R wave in V1
A 19-year-old woman with no significant cardiac or pulmonary history presented with exertional dyspnea, which had begun a few months earlier. Auscultation revealed a loud pulmonary component of the second heart sound and a diastolic murmur heard along the upper left sternal border. Her 12-lead electrocardiogram is shown in Figure 1.
Q: Which of the following can cause prominent R waves in lead V1?
- Normal variant in young adults
- Wolff-Parkinson-White syndrome
- Posterior wall myocardial infarction
- Right ventricular hypertrophy
- All of the above
A: The correct answer is all of the above.
The patient’s electrocardiogram shows a right atrial abnormality and right ventricular hypertrophy. Right atrial enlargement is evidenced by a prominent initial P wave in V1 with an amplitude of at least 1.5 mm (0.15 mV). A P wave taller than 2.5 mm (0.25 mV) in lead II may also suggest a right atrial abnormality.1
Multiple criteria exist for the diagnosis of right ventricular hypertrophy. Tall R waves in V1 with an R/S ratio greater than 1 (ie, the R wave amplitude is more than the S wave depth) is commonly used.2 Deep S waves with an R/S ratio less than 1 in V6 is another criterion. Tall R waves of amplitude greater than 7 mm in V1 by themselves may represent right ventricular hypertrophy. Most of the electrocardiographic criteria are specific but not sensitive for this diagnosis.3
Other causes of tall R waves in V1 are given in Table 1.
Q: Which of the following diseases can present with an electrocardiographic pattern of right ventricular hypertrophy in young patients?
- Pulmonary hypertension
- Atrial septal defect
- Tetralogy of Fallot
- Pulmonary stenosis
- All of the above
A: The correct answer is all of the above.4
Our patient underwent multiple investigations. On echocardiography, her estimated right ventricular pressure was 80 mm Hg, and on cardiac catheterization her mean pulmonary arterial pressure was 55 mm Hg and her pulmonary capillary wedge pressure was 6 mm Hg. She was diagnosed with pulmonary arterial hypertension, which was the cause of her right ventricular hypertrophy. She eventually underwent bilateral lung transplantation.
- Hancock EW, Deal BJ, Mirvis DM, et al; American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; American College of Cardiology Foundation; Heart Rhythm Society. AHA/ ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation 2009; 119:e251–e261.
- Milnor WR. Electrocardiogram and vectorcardiogram in right ventricular hypertrophy and right bundle-branch block. Circulation 1957; 16:348–367.
- Lehtonen J, Sutinen S, Ikäheimo M, Pääkkö P. Electrocardiographic criteria for the diagnosis of right ventricular hypertrophy verified at autopsy. Chest 1988; 93:839–842.
- Webb G, Gatzoulis MA. Atrial septal defects in the adult: recent progress and overview. Circulation 2006; 114:1645–1653.
A 19-year-old woman with no significant cardiac or pulmonary history presented with exertional dyspnea, which had begun a few months earlier. Auscultation revealed a loud pulmonary component of the second heart sound and a diastolic murmur heard along the upper left sternal border. Her 12-lead electrocardiogram is shown in Figure 1.
Q: Which of the following can cause prominent R waves in lead V1?
- Normal variant in young adults
- Wolff-Parkinson-White syndrome
- Posterior wall myocardial infarction
- Right ventricular hypertrophy
- All of the above
A: The correct answer is all of the above.
The patient’s electrocardiogram shows a right atrial abnormality and right ventricular hypertrophy. Right atrial enlargement is evidenced by a prominent initial P wave in V1 with an amplitude of at least 1.5 mm (0.15 mV). A P wave taller than 2.5 mm (0.25 mV) in lead II may also suggest a right atrial abnormality.1
Multiple criteria exist for the diagnosis of right ventricular hypertrophy. Tall R waves in V1 with an R/S ratio greater than 1 (ie, the R wave amplitude is more than the S wave depth) is commonly used.2 Deep S waves with an R/S ratio less than 1 in V6 is another criterion. Tall R waves of amplitude greater than 7 mm in V1 by themselves may represent right ventricular hypertrophy. Most of the electrocardiographic criteria are specific but not sensitive for this diagnosis.3
Other causes of tall R waves in V1 are given in Table 1.
Q: Which of the following diseases can present with an electrocardiographic pattern of right ventricular hypertrophy in young patients?
- Pulmonary hypertension
- Atrial septal defect
- Tetralogy of Fallot
- Pulmonary stenosis
- All of the above
A: The correct answer is all of the above.4
Our patient underwent multiple investigations. On echocardiography, her estimated right ventricular pressure was 80 mm Hg, and on cardiac catheterization her mean pulmonary arterial pressure was 55 mm Hg and her pulmonary capillary wedge pressure was 6 mm Hg. She was diagnosed with pulmonary arterial hypertension, which was the cause of her right ventricular hypertrophy. She eventually underwent bilateral lung transplantation.
A 19-year-old woman with no significant cardiac or pulmonary history presented with exertional dyspnea, which had begun a few months earlier. Auscultation revealed a loud pulmonary component of the second heart sound and a diastolic murmur heard along the upper left sternal border. Her 12-lead electrocardiogram is shown in Figure 1.
Q: Which of the following can cause prominent R waves in lead V1?
- Normal variant in young adults
- Wolff-Parkinson-White syndrome
- Posterior wall myocardial infarction
- Right ventricular hypertrophy
- All of the above
A: The correct answer is all of the above.
The patient’s electrocardiogram shows a right atrial abnormality and right ventricular hypertrophy. Right atrial enlargement is evidenced by a prominent initial P wave in V1 with an amplitude of at least 1.5 mm (0.15 mV). A P wave taller than 2.5 mm (0.25 mV) in lead II may also suggest a right atrial abnormality.1
Multiple criteria exist for the diagnosis of right ventricular hypertrophy. Tall R waves in V1 with an R/S ratio greater than 1 (ie, the R wave amplitude is more than the S wave depth) is commonly used.2 Deep S waves with an R/S ratio less than 1 in V6 is another criterion. Tall R waves of amplitude greater than 7 mm in V1 by themselves may represent right ventricular hypertrophy. Most of the electrocardiographic criteria are specific but not sensitive for this diagnosis.3
Other causes of tall R waves in V1 are given in Table 1.
Q: Which of the following diseases can present with an electrocardiographic pattern of right ventricular hypertrophy in young patients?
- Pulmonary hypertension
- Atrial septal defect
- Tetralogy of Fallot
- Pulmonary stenosis
- All of the above
A: The correct answer is all of the above.4
Our patient underwent multiple investigations. On echocardiography, her estimated right ventricular pressure was 80 mm Hg, and on cardiac catheterization her mean pulmonary arterial pressure was 55 mm Hg and her pulmonary capillary wedge pressure was 6 mm Hg. She was diagnosed with pulmonary arterial hypertension, which was the cause of her right ventricular hypertrophy. She eventually underwent bilateral lung transplantation.
- Hancock EW, Deal BJ, Mirvis DM, et al; American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; American College of Cardiology Foundation; Heart Rhythm Society. AHA/ ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation 2009; 119:e251–e261.
- Milnor WR. Electrocardiogram and vectorcardiogram in right ventricular hypertrophy and right bundle-branch block. Circulation 1957; 16:348–367.
- Lehtonen J, Sutinen S, Ikäheimo M, Pääkkö P. Electrocardiographic criteria for the diagnosis of right ventricular hypertrophy verified at autopsy. Chest 1988; 93:839–842.
- Webb G, Gatzoulis MA. Atrial septal defects in the adult: recent progress and overview. Circulation 2006; 114:1645–1653.
- Hancock EW, Deal BJ, Mirvis DM, et al; American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; American College of Cardiology Foundation; Heart Rhythm Society. AHA/ ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation 2009; 119:e251–e261.
- Milnor WR. Electrocardiogram and vectorcardiogram in right ventricular hypertrophy and right bundle-branch block. Circulation 1957; 16:348–367.
- Lehtonen J, Sutinen S, Ikäheimo M, Pääkkö P. Electrocardiographic criteria for the diagnosis of right ventricular hypertrophy verified at autopsy. Chest 1988; 93:839–842.
- Webb G, Gatzoulis MA. Atrial septal defects in the adult: recent progress and overview. Circulation 2006; 114:1645–1653.
Epiphyseal Chondromyxoid Fibroma With Prominent Adipose Tissue: An Unusual Radiologic and Histologic Presentation
CORE320: CT angiography bests SPECT for CAD diagnosis
SAN FRANCISCO – Coronary CT angiography outperformed myocardial perfusion single-photon emission CT for the diagnosis of obstructive coronary artery disease in a prospective multicenter head-to-head comparative study.
The CORE320 (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion) study included 381 patients with suspected or known coronary artery disease (CAD) who were scheduled for invasive quantitative coronary angiography. But first they all underwent coronary CT angiography (CTA) and single-photon emission CT (SPECT), with images analyzed in blinded independent core laboratories. The time interval between the two imaging studies was a mean of 9.4 days. Invasive coronary angiography served as the diagnostic reference standard in the 16-center, 8-country study, Dr. Marcelo F. Di Carli explained at the annual meeting of the American College of Cardiology.
The primary study endpoint was test accuracy as defined by the area under the receiver operating characteristic curve for identifying the 59% of subjects with at least a 50% stenosis by invasive coronary angiography. The rate was significantly better for CTA than SPECT: 89% vs. 69%.
CTA’s superior performance was driven by its greater sensitivity in detecting stenoses of 50% or more: 91% vs. 62% for SPECT. The two imaging modalities displayed similar specificity: 74% for CTA and 67% for SPECT.
CTA had a positive predictive value of 83% and a negative predictive value of 85%, compared with 73% and 55%, respectively, for SPECT, according to Dr. Di Carli of Brigham and Women’s Hospital, Boston.
The same pattern of results was seen with regard to diagnostic accuracy in detecting patients with at least a 70% stenosis, a prespecified secondary endpoint. CTA had 94% sensitivity, 60% specificity, a positive predictive value of 66%, and a negative predictive value of 92%. SPECT showed 72% sensitivity, 67% specificity, a 64% positive predictive value, and a 73% negative predictive value.
The average radiation dose was markedly lower with CTA: 3.54 mSv compared with 10.48 mSv for SPECT.
The study was funded by Toshiba. Dr. Di Carli reported having no relevant financial conflicts.
SAN FRANCISCO – Coronary CT angiography outperformed myocardial perfusion single-photon emission CT for the diagnosis of obstructive coronary artery disease in a prospective multicenter head-to-head comparative study.
The CORE320 (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion) study included 381 patients with suspected or known coronary artery disease (CAD) who were scheduled for invasive quantitative coronary angiography. But first they all underwent coronary CT angiography (CTA) and single-photon emission CT (SPECT), with images analyzed in blinded independent core laboratories. The time interval between the two imaging studies was a mean of 9.4 days. Invasive coronary angiography served as the diagnostic reference standard in the 16-center, 8-country study, Dr. Marcelo F. Di Carli explained at the annual meeting of the American College of Cardiology.
The primary study endpoint was test accuracy as defined by the area under the receiver operating characteristic curve for identifying the 59% of subjects with at least a 50% stenosis by invasive coronary angiography. The rate was significantly better for CTA than SPECT: 89% vs. 69%.
CTA’s superior performance was driven by its greater sensitivity in detecting stenoses of 50% or more: 91% vs. 62% for SPECT. The two imaging modalities displayed similar specificity: 74% for CTA and 67% for SPECT.
CTA had a positive predictive value of 83% and a negative predictive value of 85%, compared with 73% and 55%, respectively, for SPECT, according to Dr. Di Carli of Brigham and Women’s Hospital, Boston.
The same pattern of results was seen with regard to diagnostic accuracy in detecting patients with at least a 70% stenosis, a prespecified secondary endpoint. CTA had 94% sensitivity, 60% specificity, a positive predictive value of 66%, and a negative predictive value of 92%. SPECT showed 72% sensitivity, 67% specificity, a 64% positive predictive value, and a 73% negative predictive value.
The average radiation dose was markedly lower with CTA: 3.54 mSv compared with 10.48 mSv for SPECT.
The study was funded by Toshiba. Dr. Di Carli reported having no relevant financial conflicts.
SAN FRANCISCO – Coronary CT angiography outperformed myocardial perfusion single-photon emission CT for the diagnosis of obstructive coronary artery disease in a prospective multicenter head-to-head comparative study.
The CORE320 (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion) study included 381 patients with suspected or known coronary artery disease (CAD) who were scheduled for invasive quantitative coronary angiography. But first they all underwent coronary CT angiography (CTA) and single-photon emission CT (SPECT), with images analyzed in blinded independent core laboratories. The time interval between the two imaging studies was a mean of 9.4 days. Invasive coronary angiography served as the diagnostic reference standard in the 16-center, 8-country study, Dr. Marcelo F. Di Carli explained at the annual meeting of the American College of Cardiology.
The primary study endpoint was test accuracy as defined by the area under the receiver operating characteristic curve for identifying the 59% of subjects with at least a 50% stenosis by invasive coronary angiography. The rate was significantly better for CTA than SPECT: 89% vs. 69%.
CTA’s superior performance was driven by its greater sensitivity in detecting stenoses of 50% or more: 91% vs. 62% for SPECT. The two imaging modalities displayed similar specificity: 74% for CTA and 67% for SPECT.
CTA had a positive predictive value of 83% and a negative predictive value of 85%, compared with 73% and 55%, respectively, for SPECT, according to Dr. Di Carli of Brigham and Women’s Hospital, Boston.
The same pattern of results was seen with regard to diagnostic accuracy in detecting patients with at least a 70% stenosis, a prespecified secondary endpoint. CTA had 94% sensitivity, 60% specificity, a positive predictive value of 66%, and a negative predictive value of 92%. SPECT showed 72% sensitivity, 67% specificity, a 64% positive predictive value, and a 73% negative predictive value.
The average radiation dose was markedly lower with CTA: 3.54 mSv compared with 10.48 mSv for SPECT.
The study was funded by Toshiba. Dr. Di Carli reported having no relevant financial conflicts.
AT ACC 13
Major Finding: Coronary CT angiography had a 91% sensitivity and a 74% specificity for the detection of at least 50% stenosis in 381 patients with known or suspected CAD, superior to the 62% sensitivity and 67% specificity for myocardial perfusion single-photon emission CT in the same patients.
Data Source: CORE320, an ongoing prospective 16-center study comparing the diagnostic accuracy of two widely utilized noninvasive imaging methods in detecting obstructive CAD, with invasive quantitative coronary angiography serving as the reference standard.
Disclosures: The study is funded by Toshiba. The presenter reported having no relevant financial conflicts.
One-year outcomes support emergency department CCTA
SAN FRANCISCO – Coronary CT angiography works better than traditional rule-out approaches for identifying emergency department patients with chest pain who are free of significant coronary disease, according to 1-year results from a randomized comparison of more than 1,300 patients.
The results also show that relying on coronary CT angiography (CCTA) for emergency department assessment of coronary disease is safe, with a 1-year rate of death or myocardial infarction substantially below 1% in patients judged negative for coronary disease by CCTA, Dr. Judd E. Hollander said at the annual meeting of the American College of Cardiology.
The findings confirmed and extended the 30-day results reported a year ago from the same study, the American College of Radiology Imaging Network (ACRIN) PA 4005 study, which randomized 1,370 low- to intermediate-risk patients who presented with chest pain and possible acute coronary syndrome at any of five U.S. emergency departments.
Two-thirds of the patients were randomized to assessment that included CCTA when deemed necessary, while the remaining third underwent more traditional assessment that could include an exercise treadmill test, a stress test with imaging, and stress echocardiography.
While the results supported a role for routine use of CCTA for assessing the types of patients enrolled in the study, Dr. Hollander stressed that a CCTA is not needed for every ED patient with questionable chest pain.
"We try to use this as an exclusionary test for patients who need an exclusionary test," said Dr. Hollander, professor and clinical research director in the department of emergency medicine at the University of Pennsylvania in Philadelphia.
"We want to avoid making this like a d-dimer test [for thrombus] or CT perfusion [for stroke patients], where everyone who comes into the ED with appropriate signs and symptoms gets one. We don’t use CCTA on patients we normally discharge. There is the risk from radiation. You need to ask how much do you need to find out what is going on with the patient sooner rather than later," he said.
During year-long follow-up on 1,368 of the starting ACRIN patients (one patient was lost to follow-up from each randomization group), one cardiac death and one myocardial infarction occurred among the 825 patients randomized to the CCTA arm and declared free of coronary disease, a 0.2% rate that fell within the study’s prespecified safety criterion of less than 1%.
CCTA’s 1-year safety came without any boost in resource use compared with ED chest-pain patients assessed by conventional means. Overall use of cardiac testing, hospital readmissions, revascularization, and ED visits was similar during 1-year follow-up in the two treatment arms, Dr. Hollander said. Further breakdown of the resource-use data showed that the majority of medical activity following the index hospitalization occurred in the 9% of the initial patients identified with coronary disease by CCTA. Fewer resources were used in patients who had questionable coronary disease following CCTA, and the least amount of resource use occurred in patients without coronary disease by CCTA.
Because CCTA categorized 9% of patients in that study arm as having coronary disease compared with 3% of the control group, and since 77% of patients in the CCTA arm were judged free of coronary disease compared with 61% in the control arm, CCTA "shifts resources to where they are most useful, with more coronary artery disease identified and treated and more patients without disease not receiving treatment," Dr. Hollander said.
The initial, 30-day ACRIN report said that 50% of patients managed in the CCTA arm were discharged early from the ED, compared with 23% of the control group (N. Engl. J. Med. 2012;366:1393-403). Patients in the CCTA group also had a substantially shorter average length of stay during their initial hospital visit.
The ACRIN PA 4005 study was sponsored by the Pennsylvania Department of Health and the ACRIN Foundation. Dr. Hollander said that he has also been a consultant to Behring, Janssen, Luitpold, and Radiometer, and that he has received research funding from Abbott, Alere, Brahms, and Siemens.
On Twitter @mitchelzoler
SAN FRANCISCO – Coronary CT angiography works better than traditional rule-out approaches for identifying emergency department patients with chest pain who are free of significant coronary disease, according to 1-year results from a randomized comparison of more than 1,300 patients.
The results also show that relying on coronary CT angiography (CCTA) for emergency department assessment of coronary disease is safe, with a 1-year rate of death or myocardial infarction substantially below 1% in patients judged negative for coronary disease by CCTA, Dr. Judd E. Hollander said at the annual meeting of the American College of Cardiology.
The findings confirmed and extended the 30-day results reported a year ago from the same study, the American College of Radiology Imaging Network (ACRIN) PA 4005 study, which randomized 1,370 low- to intermediate-risk patients who presented with chest pain and possible acute coronary syndrome at any of five U.S. emergency departments.
Two-thirds of the patients were randomized to assessment that included CCTA when deemed necessary, while the remaining third underwent more traditional assessment that could include an exercise treadmill test, a stress test with imaging, and stress echocardiography.
While the results supported a role for routine use of CCTA for assessing the types of patients enrolled in the study, Dr. Hollander stressed that a CCTA is not needed for every ED patient with questionable chest pain.
"We try to use this as an exclusionary test for patients who need an exclusionary test," said Dr. Hollander, professor and clinical research director in the department of emergency medicine at the University of Pennsylvania in Philadelphia.
"We want to avoid making this like a d-dimer test [for thrombus] or CT perfusion [for stroke patients], where everyone who comes into the ED with appropriate signs and symptoms gets one. We don’t use CCTA on patients we normally discharge. There is the risk from radiation. You need to ask how much do you need to find out what is going on with the patient sooner rather than later," he said.
During year-long follow-up on 1,368 of the starting ACRIN patients (one patient was lost to follow-up from each randomization group), one cardiac death and one myocardial infarction occurred among the 825 patients randomized to the CCTA arm and declared free of coronary disease, a 0.2% rate that fell within the study’s prespecified safety criterion of less than 1%.
CCTA’s 1-year safety came without any boost in resource use compared with ED chest-pain patients assessed by conventional means. Overall use of cardiac testing, hospital readmissions, revascularization, and ED visits was similar during 1-year follow-up in the two treatment arms, Dr. Hollander said. Further breakdown of the resource-use data showed that the majority of medical activity following the index hospitalization occurred in the 9% of the initial patients identified with coronary disease by CCTA. Fewer resources were used in patients who had questionable coronary disease following CCTA, and the least amount of resource use occurred in patients without coronary disease by CCTA.
Because CCTA categorized 9% of patients in that study arm as having coronary disease compared with 3% of the control group, and since 77% of patients in the CCTA arm were judged free of coronary disease compared with 61% in the control arm, CCTA "shifts resources to where they are most useful, with more coronary artery disease identified and treated and more patients without disease not receiving treatment," Dr. Hollander said.
The initial, 30-day ACRIN report said that 50% of patients managed in the CCTA arm were discharged early from the ED, compared with 23% of the control group (N. Engl. J. Med. 2012;366:1393-403). Patients in the CCTA group also had a substantially shorter average length of stay during their initial hospital visit.
The ACRIN PA 4005 study was sponsored by the Pennsylvania Department of Health and the ACRIN Foundation. Dr. Hollander said that he has also been a consultant to Behring, Janssen, Luitpold, and Radiometer, and that he has received research funding from Abbott, Alere, Brahms, and Siemens.
On Twitter @mitchelzoler
SAN FRANCISCO – Coronary CT angiography works better than traditional rule-out approaches for identifying emergency department patients with chest pain who are free of significant coronary disease, according to 1-year results from a randomized comparison of more than 1,300 patients.
The results also show that relying on coronary CT angiography (CCTA) for emergency department assessment of coronary disease is safe, with a 1-year rate of death or myocardial infarction substantially below 1% in patients judged negative for coronary disease by CCTA, Dr. Judd E. Hollander said at the annual meeting of the American College of Cardiology.
The findings confirmed and extended the 30-day results reported a year ago from the same study, the American College of Radiology Imaging Network (ACRIN) PA 4005 study, which randomized 1,370 low- to intermediate-risk patients who presented with chest pain and possible acute coronary syndrome at any of five U.S. emergency departments.
Two-thirds of the patients were randomized to assessment that included CCTA when deemed necessary, while the remaining third underwent more traditional assessment that could include an exercise treadmill test, a stress test with imaging, and stress echocardiography.
While the results supported a role for routine use of CCTA for assessing the types of patients enrolled in the study, Dr. Hollander stressed that a CCTA is not needed for every ED patient with questionable chest pain.
"We try to use this as an exclusionary test for patients who need an exclusionary test," said Dr. Hollander, professor and clinical research director in the department of emergency medicine at the University of Pennsylvania in Philadelphia.
"We want to avoid making this like a d-dimer test [for thrombus] or CT perfusion [for stroke patients], where everyone who comes into the ED with appropriate signs and symptoms gets one. We don’t use CCTA on patients we normally discharge. There is the risk from radiation. You need to ask how much do you need to find out what is going on with the patient sooner rather than later," he said.
During year-long follow-up on 1,368 of the starting ACRIN patients (one patient was lost to follow-up from each randomization group), one cardiac death and one myocardial infarction occurred among the 825 patients randomized to the CCTA arm and declared free of coronary disease, a 0.2% rate that fell within the study’s prespecified safety criterion of less than 1%.
CCTA’s 1-year safety came without any boost in resource use compared with ED chest-pain patients assessed by conventional means. Overall use of cardiac testing, hospital readmissions, revascularization, and ED visits was similar during 1-year follow-up in the two treatment arms, Dr. Hollander said. Further breakdown of the resource-use data showed that the majority of medical activity following the index hospitalization occurred in the 9% of the initial patients identified with coronary disease by CCTA. Fewer resources were used in patients who had questionable coronary disease following CCTA, and the least amount of resource use occurred in patients without coronary disease by CCTA.
Because CCTA categorized 9% of patients in that study arm as having coronary disease compared with 3% of the control group, and since 77% of patients in the CCTA arm were judged free of coronary disease compared with 61% in the control arm, CCTA "shifts resources to where they are most useful, with more coronary artery disease identified and treated and more patients without disease not receiving treatment," Dr. Hollander said.
The initial, 30-day ACRIN report said that 50% of patients managed in the CCTA arm were discharged early from the ED, compared with 23% of the control group (N. Engl. J. Med. 2012;366:1393-403). Patients in the CCTA group also had a substantially shorter average length of stay during their initial hospital visit.
The ACRIN PA 4005 study was sponsored by the Pennsylvania Department of Health and the ACRIN Foundation. Dr. Hollander said that he has also been a consultant to Behring, Janssen, Luitpold, and Radiometer, and that he has received research funding from Abbott, Alere, Brahms, and Siemens.
On Twitter @mitchelzoler
AT ACC 13
Major finding: Patients negative for coronary disease by CT angiography had a 0.2% rate of cardiac death or myocardial infarction at 1-year follow-up.
Data source: The ACRIN PA 4005 study, which followed 1,368 chest-pain patients for 1 year after randomization to coronary CT angiography or conventional emergency department assessment.
Disclosures: The ACRIN PA 4005 study was sponsored by the Pennsylvania Department of Health and the ACRIN Foundation. Dr. Hollander said that he has also been a consultant to Behring, Janssen, Luitpold, and Radiometer, and that he has received research funding from Abbott, Alere, Brahms, and Siemens.
Enhanced cardiac MR indicates dilated myopathy risk, identifies salvageable LV walls
By identifying cardiac fibrosis, cardiovascular magnetic resonance imaging with late gadolinium enhancement proved to be a useful cardiac assessment tool in two studies published in the March 6 edition of JAMA.
In the first, British researchers from London’s Royal Brompton Hospital and elsewhere used cardiovascular magnetic resonance imaging with late gadolinium enhancement [LGE-CMR] to detect and quantify midwall fibrosis in patients with dilated cardiomyopathy. They found that doing so "provided independent prognostic information beyond LVEF" – left ventricular ejection fraction, the basis of current risk stratification schemes –in patients with nonischemic dilated cardiomyopathy.
Separately, American investigators used the same technology in coronary artery disease patients to assess the extent of scarring in their thinned left ventricular walls. They found that "myocardial regions with severe wall thinning do not necessarily consist entirely of scar tissue but instead may have minimal or no scarring," which is inconsistent with current assumptions that thinned regions are made of permanent scar tissue and have no residual viability.
The British group, led by Dr. Ankur Gulati of Royal Brompton Hospital in London, followed 472 patients with dilated cardiomyopathy, assessed at baseline for midwall fibrosis, for a median of 5.3 years.
Thirty-eight of the 142 patients (27%) found to have midwall fibrosis – but only 35 of 330 (11%) without it – died during the trial. Adjusted for LVEF and other conventional prognostic factors, both fibrosis presence (hazard ratio 2.43) and extent (HR, 1.11) were independently and incrementally associated with all-cause mortality. Midwall fibrosis increased by more than five times the likelihood of sudden or aborted cardiac death (JAMA 2013;309:896-908).
LGE-CMR also appeared to "facilitate identification of high-risk patients with milder degrees of left ventricular dysfunction who are currently overlooked by assessment of global left ventricular function alone, Dr. Gulati and colleagues wrote, noting that use of the technology could help guide patient selection for implantable cardioverter defibrillators. Addition of fibrosis to LVEF also significantly improved risk reclassification, they said.
The Duke team, led by Dr. Dipan J. Shah of the Duke Cardiovascular Magnetic Resonance Center in Durham, N.C., followed 201 ischemic heart disease patients with LV wall thinning spanning a mean of 34% of LV surface area; thinning was defined as a diastolic wall thickness at or below 5.5 mm. Thirty seven patients (18%) had had limited or no scar burden, defined as no more than 50% involvement.
Seventy-two of the 201 patients underwent revascularization, including revascularization of the coronary artery supplying the thinned region. Among the 14 limited-scar-burden patients who had repeat CMR-LGE afterward, diastolic wall thickness increased significantly, from 4.4 mm to 7.5 mm; their LV walls were no longer thin. A multivariate analysis showed that the extent of scarring was the strongest predictor of improvement. (JAMA 2013;309:909-18).
The function of the thin walls was also related scar burden. Limited scar burden was "strongly associated with contractile improvement and reversal of wall thinning after revascularization." The results, taken together, showed that as long there is limited scarring, the myocardial wall may thin and revert back to full thickness. Thus, myocardial thinning should not be considered permanent, they concluded.
Most of the 201 patients had significant LV dysfunction and multivessel coronary artery disease. Neither age, sex, cardiac risk factors, angina, heart failure symptoms, nor Q wave presence predicted the amount of scarring.
"The findings suggest that these clinical characteristics should not be used to assess viability in a region of thinning." They also indicate that "the end-stage of remodeling is better determined by tissue composition (i.e., scarring) rather than any set level of morphological changes to the LV cavity or LV wall," the Duke team concluded.
Members of the British team disclosed grants, consulting arrangements, and other commercial relationships with Biotronik, Boston Scientific, Roche, Servier, Celladon, AstraZeneca, GlaxoSmithKline, GE Healthcare, Bayer, ResMed, Roche Diagnostics, Pfizer, Boehringer, Novartis, Medtronic, Siemens, ApoPharma, AMAG, and Cardiovascular Imaging Solutions.
Two authors on the Duke and Northwestern team are named inventors on a Northwestern University patent for delayed-enhancement cardiovascular magnetic resonance imaging. Another reported speaker fees, consulting deals, or pending grants from Astellas, Siemens, AstraZeneca, Lantheus Medical Imaging, and Takeda.
Although these two imaging studies add to our knowledge of how supplemental noninvasive imaging studies can help cardiovascular specialists, "the clinical challenge remains in deciding which patients to evaluate with CMR and LGE and what to do with the findings," wrote Dr. Deepak Gupta, Dr. Raymond Kwong, and Dr. Marc Pfeffer.
The dilated cardiomyopathy (DCM) study, they note, did not take into consideration "proven and readily available" risk markers, such as recent hospitalization, renal function, and medication use. In addition, the study "was not powered nor designed to investigate the additional benefit of CMR beyond current class I indications for cardioverter-defibrillator therapy in DCM patients." Therefore, the data are "not sufficiently robust" to support the authors’ suggestion that LGE-CMR "may refine" the sudden cardiac death risk estimate ... [and] could guide [cardioverter defibrillator] implantation."
Regarding the thinned left ventricular wall study, the investigators failed to make clear whether all of the thinned segments assessed in this analysis were also akinetic, "which is generally considered as part of the criteria for nonviable myocardium. Furthermore, and perhaps most important, in the context of the results from [a recent] trial addressing the value of viability assessments in guiding revascularization decisions (N. Engl. J. Med. 2011;364:1617-25), the clinician is still left trying to decide what to do with a finding of viable myocardium.
Together, the two studies "provide a consistent message that detailed assessments of tissue composition, in particular fibrosis by LGE, may provide superior information than morphologic parameters, in both ischemic and nonischemic cardiomyopathies. CMR with LGE imaging adds to the practitioner’s armamentarium for assessment of cardiac structure and function and augments diagnostic and prognostic capabilities."
Dr. Gupta, Dr. Kwong, and Dr. Pfeffer, of the Division of Cardiovascular Medicine at Brigham and Women’s Hospital in Boston, made these comments in an editorial accompanying the two imaging studies (JAMA. 2013;309:929-30). They reported no disclosures.
Although these two imaging studies add to our knowledge of how supplemental noninvasive imaging studies can help cardiovascular specialists, "the clinical challenge remains in deciding which patients to evaluate with CMR and LGE and what to do with the findings," wrote Dr. Deepak Gupta, Dr. Raymond Kwong, and Dr. Marc Pfeffer.
The dilated cardiomyopathy (DCM) study, they note, did not take into consideration "proven and readily available" risk markers, such as recent hospitalization, renal function, and medication use. In addition, the study "was not powered nor designed to investigate the additional benefit of CMR beyond current class I indications for cardioverter-defibrillator therapy in DCM patients." Therefore, the data are "not sufficiently robust" to support the authors’ suggestion that LGE-CMR "may refine" the sudden cardiac death risk estimate ... [and] could guide [cardioverter defibrillator] implantation."
Regarding the thinned left ventricular wall study, the investigators failed to make clear whether all of the thinned segments assessed in this analysis were also akinetic, "which is generally considered as part of the criteria for nonviable myocardium. Furthermore, and perhaps most important, in the context of the results from [a recent] trial addressing the value of viability assessments in guiding revascularization decisions (N. Engl. J. Med. 2011;364:1617-25), the clinician is still left trying to decide what to do with a finding of viable myocardium.
Together, the two studies "provide a consistent message that detailed assessments of tissue composition, in particular fibrosis by LGE, may provide superior information than morphologic parameters, in both ischemic and nonischemic cardiomyopathies. CMR with LGE imaging adds to the practitioner’s armamentarium for assessment of cardiac structure and function and augments diagnostic and prognostic capabilities."
Dr. Gupta, Dr. Kwong, and Dr. Pfeffer, of the Division of Cardiovascular Medicine at Brigham and Women’s Hospital in Boston, made these comments in an editorial accompanying the two imaging studies (JAMA. 2013;309:929-30). They reported no disclosures.
Although these two imaging studies add to our knowledge of how supplemental noninvasive imaging studies can help cardiovascular specialists, "the clinical challenge remains in deciding which patients to evaluate with CMR and LGE and what to do with the findings," wrote Dr. Deepak Gupta, Dr. Raymond Kwong, and Dr. Marc Pfeffer.
The dilated cardiomyopathy (DCM) study, they note, did not take into consideration "proven and readily available" risk markers, such as recent hospitalization, renal function, and medication use. In addition, the study "was not powered nor designed to investigate the additional benefit of CMR beyond current class I indications for cardioverter-defibrillator therapy in DCM patients." Therefore, the data are "not sufficiently robust" to support the authors’ suggestion that LGE-CMR "may refine" the sudden cardiac death risk estimate ... [and] could guide [cardioverter defibrillator] implantation."
Regarding the thinned left ventricular wall study, the investigators failed to make clear whether all of the thinned segments assessed in this analysis were also akinetic, "which is generally considered as part of the criteria for nonviable myocardium. Furthermore, and perhaps most important, in the context of the results from [a recent] trial addressing the value of viability assessments in guiding revascularization decisions (N. Engl. J. Med. 2011;364:1617-25), the clinician is still left trying to decide what to do with a finding of viable myocardium.
Together, the two studies "provide a consistent message that detailed assessments of tissue composition, in particular fibrosis by LGE, may provide superior information than morphologic parameters, in both ischemic and nonischemic cardiomyopathies. CMR with LGE imaging adds to the practitioner’s armamentarium for assessment of cardiac structure and function and augments diagnostic and prognostic capabilities."
Dr. Gupta, Dr. Kwong, and Dr. Pfeffer, of the Division of Cardiovascular Medicine at Brigham and Women’s Hospital in Boston, made these comments in an editorial accompanying the two imaging studies (JAMA. 2013;309:929-30). They reported no disclosures.
By identifying cardiac fibrosis, cardiovascular magnetic resonance imaging with late gadolinium enhancement proved to be a useful cardiac assessment tool in two studies published in the March 6 edition of JAMA.
In the first, British researchers from London’s Royal Brompton Hospital and elsewhere used cardiovascular magnetic resonance imaging with late gadolinium enhancement [LGE-CMR] to detect and quantify midwall fibrosis in patients with dilated cardiomyopathy. They found that doing so "provided independent prognostic information beyond LVEF" – left ventricular ejection fraction, the basis of current risk stratification schemes –in patients with nonischemic dilated cardiomyopathy.
Separately, American investigators used the same technology in coronary artery disease patients to assess the extent of scarring in their thinned left ventricular walls. They found that "myocardial regions with severe wall thinning do not necessarily consist entirely of scar tissue but instead may have minimal or no scarring," which is inconsistent with current assumptions that thinned regions are made of permanent scar tissue and have no residual viability.
The British group, led by Dr. Ankur Gulati of Royal Brompton Hospital in London, followed 472 patients with dilated cardiomyopathy, assessed at baseline for midwall fibrosis, for a median of 5.3 years.
Thirty-eight of the 142 patients (27%) found to have midwall fibrosis – but only 35 of 330 (11%) without it – died during the trial. Adjusted for LVEF and other conventional prognostic factors, both fibrosis presence (hazard ratio 2.43) and extent (HR, 1.11) were independently and incrementally associated with all-cause mortality. Midwall fibrosis increased by more than five times the likelihood of sudden or aborted cardiac death (JAMA 2013;309:896-908).
LGE-CMR also appeared to "facilitate identification of high-risk patients with milder degrees of left ventricular dysfunction who are currently overlooked by assessment of global left ventricular function alone, Dr. Gulati and colleagues wrote, noting that use of the technology could help guide patient selection for implantable cardioverter defibrillators. Addition of fibrosis to LVEF also significantly improved risk reclassification, they said.
The Duke team, led by Dr. Dipan J. Shah of the Duke Cardiovascular Magnetic Resonance Center in Durham, N.C., followed 201 ischemic heart disease patients with LV wall thinning spanning a mean of 34% of LV surface area; thinning was defined as a diastolic wall thickness at or below 5.5 mm. Thirty seven patients (18%) had had limited or no scar burden, defined as no more than 50% involvement.
Seventy-two of the 201 patients underwent revascularization, including revascularization of the coronary artery supplying the thinned region. Among the 14 limited-scar-burden patients who had repeat CMR-LGE afterward, diastolic wall thickness increased significantly, from 4.4 mm to 7.5 mm; their LV walls were no longer thin. A multivariate analysis showed that the extent of scarring was the strongest predictor of improvement. (JAMA 2013;309:909-18).
The function of the thin walls was also related scar burden. Limited scar burden was "strongly associated with contractile improvement and reversal of wall thinning after revascularization." The results, taken together, showed that as long there is limited scarring, the myocardial wall may thin and revert back to full thickness. Thus, myocardial thinning should not be considered permanent, they concluded.
Most of the 201 patients had significant LV dysfunction and multivessel coronary artery disease. Neither age, sex, cardiac risk factors, angina, heart failure symptoms, nor Q wave presence predicted the amount of scarring.
"The findings suggest that these clinical characteristics should not be used to assess viability in a region of thinning." They also indicate that "the end-stage of remodeling is better determined by tissue composition (i.e., scarring) rather than any set level of morphological changes to the LV cavity or LV wall," the Duke team concluded.
Members of the British team disclosed grants, consulting arrangements, and other commercial relationships with Biotronik, Boston Scientific, Roche, Servier, Celladon, AstraZeneca, GlaxoSmithKline, GE Healthcare, Bayer, ResMed, Roche Diagnostics, Pfizer, Boehringer, Novartis, Medtronic, Siemens, ApoPharma, AMAG, and Cardiovascular Imaging Solutions.
Two authors on the Duke and Northwestern team are named inventors on a Northwestern University patent for delayed-enhancement cardiovascular magnetic resonance imaging. Another reported speaker fees, consulting deals, or pending grants from Astellas, Siemens, AstraZeneca, Lantheus Medical Imaging, and Takeda.
By identifying cardiac fibrosis, cardiovascular magnetic resonance imaging with late gadolinium enhancement proved to be a useful cardiac assessment tool in two studies published in the March 6 edition of JAMA.
In the first, British researchers from London’s Royal Brompton Hospital and elsewhere used cardiovascular magnetic resonance imaging with late gadolinium enhancement [LGE-CMR] to detect and quantify midwall fibrosis in patients with dilated cardiomyopathy. They found that doing so "provided independent prognostic information beyond LVEF" – left ventricular ejection fraction, the basis of current risk stratification schemes –in patients with nonischemic dilated cardiomyopathy.
Separately, American investigators used the same technology in coronary artery disease patients to assess the extent of scarring in their thinned left ventricular walls. They found that "myocardial regions with severe wall thinning do not necessarily consist entirely of scar tissue but instead may have minimal or no scarring," which is inconsistent with current assumptions that thinned regions are made of permanent scar tissue and have no residual viability.
The British group, led by Dr. Ankur Gulati of Royal Brompton Hospital in London, followed 472 patients with dilated cardiomyopathy, assessed at baseline for midwall fibrosis, for a median of 5.3 years.
Thirty-eight of the 142 patients (27%) found to have midwall fibrosis – but only 35 of 330 (11%) without it – died during the trial. Adjusted for LVEF and other conventional prognostic factors, both fibrosis presence (hazard ratio 2.43) and extent (HR, 1.11) were independently and incrementally associated with all-cause mortality. Midwall fibrosis increased by more than five times the likelihood of sudden or aborted cardiac death (JAMA 2013;309:896-908).
LGE-CMR also appeared to "facilitate identification of high-risk patients with milder degrees of left ventricular dysfunction who are currently overlooked by assessment of global left ventricular function alone, Dr. Gulati and colleagues wrote, noting that use of the technology could help guide patient selection for implantable cardioverter defibrillators. Addition of fibrosis to LVEF also significantly improved risk reclassification, they said.
The Duke team, led by Dr. Dipan J. Shah of the Duke Cardiovascular Magnetic Resonance Center in Durham, N.C., followed 201 ischemic heart disease patients with LV wall thinning spanning a mean of 34% of LV surface area; thinning was defined as a diastolic wall thickness at or below 5.5 mm. Thirty seven patients (18%) had had limited or no scar burden, defined as no more than 50% involvement.
Seventy-two of the 201 patients underwent revascularization, including revascularization of the coronary artery supplying the thinned region. Among the 14 limited-scar-burden patients who had repeat CMR-LGE afterward, diastolic wall thickness increased significantly, from 4.4 mm to 7.5 mm; their LV walls were no longer thin. A multivariate analysis showed that the extent of scarring was the strongest predictor of improvement. (JAMA 2013;309:909-18).
The function of the thin walls was also related scar burden. Limited scar burden was "strongly associated with contractile improvement and reversal of wall thinning after revascularization." The results, taken together, showed that as long there is limited scarring, the myocardial wall may thin and revert back to full thickness. Thus, myocardial thinning should not be considered permanent, they concluded.
Most of the 201 patients had significant LV dysfunction and multivessel coronary artery disease. Neither age, sex, cardiac risk factors, angina, heart failure symptoms, nor Q wave presence predicted the amount of scarring.
"The findings suggest that these clinical characteristics should not be used to assess viability in a region of thinning." They also indicate that "the end-stage of remodeling is better determined by tissue composition (i.e., scarring) rather than any set level of morphological changes to the LV cavity or LV wall," the Duke team concluded.
Members of the British team disclosed grants, consulting arrangements, and other commercial relationships with Biotronik, Boston Scientific, Roche, Servier, Celladon, AstraZeneca, GlaxoSmithKline, GE Healthcare, Bayer, ResMed, Roche Diagnostics, Pfizer, Boehringer, Novartis, Medtronic, Siemens, ApoPharma, AMAG, and Cardiovascular Imaging Solutions.
Two authors on the Duke and Northwestern team are named inventors on a Northwestern University patent for delayed-enhancement cardiovascular magnetic resonance imaging. Another reported speaker fees, consulting deals, or pending grants from Astellas, Siemens, AstraZeneca, Lantheus Medical Imaging, and Takeda.
FROM JAMA