Imaging

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

A version of this article first appeared on Medscape.com.

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

A version of this article first appeared on Medscape.com.

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

A version of this article first appeared on Medscape.com.

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

A version of this article first appeared on Medscape.com.

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

A version of this article first appeared on Medscape.com.

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

A version of this article first appeared on Medscape.com.

Virtual platforms democratized scientific meetings during the COVID-19 pandemic but, as any meeting-goer will tell you, it’s the questions from the floor and the back-and-forth of an expert panel that often reveal the importance of and/or problems with a presentation. It’s the scrutiny that makes the science resonate, especially in this postfactual era.

The all-virtual American Heart Association Scientific Sessions 2021 is looking to recreate the engagement of an in-person meeting by offering more live interactive events. They range from seven late-breaking science (LBS) sessions to Saturday’s fireside chat on the Pfizer and Moderna COVID-19 vaccines and Monday’s dive into the controversial new AHA/American College of Cardiology Chest Pain guidelines.

To help digest the latest science, attendees will be able to have their questions answered in real-time via Slido, meet with the trialists, and hear live commentary from key opinion leaders after the live events. A networking function will also allow attendees and exhibitors to chat or meet virtually.

“In this day and age, many people pretty quickly can get access to the science but it’s what I call the IC sort of phenomenon – the presentation of the information, the context of the information, putting it into how I’m going to use it in my practice, and then the critical appraisal – that’s what most people want at the Scientific Sessions,” program committee chair Manesh R. Patel, MD, of Duke University School of Medicine, said in an interview. “We’re all craving ways in which we can interact with one another to put things in context.”

Plans for a hybrid in-person meeting in Boston were scuttled in September because of the Delta variant surge, but the theme of the meeting remained: “One World. Together for Science.” Attendees will be able to access more than 500 live and on-demand sessions including 117 oral abstracts, 286 poster sessions, 59 moderated digital posters, and over a dozen sessions focused on strategies to promote health equity.

“Last year there was a Presidential Session and a statement on structural racism, so we wanted to take the next step and say, What are the ways in which people are starting to interact and do things to make a difference?” explained Dr. Patel. “So, this year, you’ll see different versions of that from the Main Event session, which has some case vignettes and a panel discussion, to other health equity sessions that describe not just COVID care, but blood pressure care, maternal-fetal medicine, and congenital kids. Wherever we can, we’ve tried to infuse it throughout the sessions and will continue to.”

Late-breaking science

The LBS sessions kick off at 9:30 a.m. ET Saturday with AVATAR, a randomized trial of aortic valve replacement vs. watchful waiting in severe aortic stenosis proved asymptomatic through exercise testing.

“The findings of that trial, depending on what they are, could certainly impact clinical practice because it’s a very common scenario in which we have elderly patients with aortic valve stenosis that might be severe but they may not be symptomatic,” he said.

It’s followed by a randomized trial from the Cardiothoracic Surgical Trials Network, examining whether tricuspid repair at the time of mitral valve surgery leads to beneficial outcomes. “I think it’s a pretty important study,” Dr. Patel said, “because it’ll again affect how we think about our clinical practice.”

Rounding out the LBS.01 session is RAPID CABG, comparing early vs. delayed coronary bypass graft surgery (CABG) in patients with acute coronary syndromes on ticagrelor, and the pivotal U.S. VEST trial of an external support device already approved in Europe for saphenous vein grafts during CABG.

Saturday’s LBS.02 at 3:00 p.m. ET is devoted to hypertension and looks at how the COVID-19 pandemic affected blood pressure control. There’s also a study of remotely delivered hypertension and lipid management in 10,000 patients across the Partners Healthcare System and a cluster randomized trial of a village doctor–led blood pressure intervention in rural China.

Sunday’s LBS.03 at 8:00 a.m. ET is focused on atrial arrhythmias, starting with the CRAVE trial examining the effect of caffeine consumption on cardiac ectopy burden in 108 patients using an N-of-1 design and 2-day blocks on and off caffeine. “There’s an ability to identify a dose response that you get arrhythmias when you increase the amount of coffee you drink vs. not in an individual, so I think that will be likely discussed a lot and worth paying attention to,” Dr. Patel said.

The session also includes GIRAF, a comparison of cognitive outcomes with dabigatran (Pradaxa) vs. warfarin (Coumadin) in nonvalvular atrial fibrillation (AF); PALACS, a randomized trial examining whether left-sided pericardiotomy prevents AF after cardiac surgery; and AMAZE, which study sponsor AtriCure revealed missed its primary efficacy endpoint of freedom from AF with the LARIAT suture delivery device for left atrial appendage closure plus pulmonary vein isolation.

LBS.04 at 3:30 p.m. ET Sunday takes on digital health, with results from the nonrandomized Fitbit Heart Study on AF notifications from 450,000 participants wearing a single-lead ECG patch. “A lot of technologies claim that they can detect things, and we should ask that people go through the rigorous evaluation to see if they in fact do. So, in that respect, I think it›s an important step,” observed Dr. Patel.

Also on tap is I-STOP-AFib, another N-of-1 study using mobile apps and the AliveCor device to identify individual AF triggers; and REVeAL-HF, a 4,000-patient study examining whether electronic alerts that provide clinicians with prognostic information on their heart failure (HF) patients will reduce mortality and 30-day HF hospitalizations.

LBS.05 at 5:00 p.m. ET provides new information from EMPEROR-Preserved in HF with preserved ejection fraction and main results from EMPULSE, also using the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in 530 patients hospitalized for acute HF.

The session also features CHIEF-HF, a randomized trial leveraging mobile technologies to test whether 12 weeks of another SGLT2 inhibitor, canagliflozin (Invokana), is superior to placebo for improving HF symptoms; and DREAM-HF, a comparison of transendocardial delivery of allogeneic mesenchymal precursor cells vs. a sham comparator in chronic HF as a result of left ventricular systolic dysfunction.

Monday’s LBS.06 at 8:00 a.m. ET details the safety and cholesterol-lowering efficacy of MK-0616, an investigational oral PCSK9 inhibitor. “It’s just a phase 2 [trial], but there’s interest in an oral PCSK9 inhibitor, given that the current ones are subcutaneous,” Dr. Patel said.

Results will also be presented from PREPARE-IT 2, which tested icosapent ethyl vs. placebo in outpatients with COVID-19. In the recently reported PREPARE-IT 1, a loading dose of icosapent ethyl failed to reduce the risk of hospitalization with SARS-CoV-2 infection among at-risk individuals.

LBS.07 at 11:00 a.m. Monday completes the late-breakers with new results from ASCEND, this time examining the effect of aspirin on dementia and cognitive impairment in patients with diabetes.

Next up is a look at the effectiveness of P2Y12 inhibitors in hospitalized patients with COVID-19 in the adaptive ACTIV-4a trial, followed by results of the pivotal phase 3 REVERSE-IT trial of bentracimab, a recombinant human monoclonal antibody antigen fragment designed to reverse the antiplatelet activity of ticagrelor in the event of major bleeding or when urgent surgery is needed.

Closing out the session is AXIOMATIC-TKR, a double-blind comparison of the safety and efficacy of the investigational oral factor XI anticoagulant JNJ-70033093 vs. subcutaneous enoxaparin (Lovenox) in elective total knee replacement.

For those searching for more AHA-related science online, the Resuscitation Science Symposium (ReSS) will run from this Friday through Sunday and the Quality of Care and Outcomes Research (QCOR) Scientific Sessions will take the stage next Monday, Nov. 15.

A version of this article first appeared on Medscape.com.

Virtual platforms democratized scientific meetings during the COVID-19 pandemic but, as any meeting-goer will tell you, it’s the questions from the floor and the back-and-forth of an expert panel that often reveal the importance of and/or problems with a presentation. It’s the scrutiny that makes the science resonate, especially in this postfactual era.

The all-virtual American Heart Association Scientific Sessions 2021 is looking to recreate the engagement of an in-person meeting by offering more live interactive events. They range from seven late-breaking science (LBS) sessions to Saturday’s fireside chat on the Pfizer and Moderna COVID-19 vaccines and Monday’s dive into the controversial new AHA/American College of Cardiology Chest Pain guidelines.

To help digest the latest science, attendees will be able to have their questions answered in real-time via Slido, meet with the trialists, and hear live commentary from key opinion leaders after the live events. A networking function will also allow attendees and exhibitors to chat or meet virtually.

“In this day and age, many people pretty quickly can get access to the science but it’s what I call the IC sort of phenomenon – the presentation of the information, the context of the information, putting it into how I’m going to use it in my practice, and then the critical appraisal – that’s what most people want at the Scientific Sessions,” program committee chair Manesh R. Patel, MD, of Duke University School of Medicine, said in an interview. “We’re all craving ways in which we can interact with one another to put things in context.”

Plans for a hybrid in-person meeting in Boston were scuttled in September because of the Delta variant surge, but the theme of the meeting remained: “One World. Together for Science.” Attendees will be able to access more than 500 live and on-demand sessions including 117 oral abstracts, 286 poster sessions, 59 moderated digital posters, and over a dozen sessions focused on strategies to promote health equity.

“Last year there was a Presidential Session and a statement on structural racism, so we wanted to take the next step and say, What are the ways in which people are starting to interact and do things to make a difference?” explained Dr. Patel. “So, this year, you’ll see different versions of that from the Main Event session, which has some case vignettes and a panel discussion, to other health equity sessions that describe not just COVID care, but blood pressure care, maternal-fetal medicine, and congenital kids. Wherever we can, we’ve tried to infuse it throughout the sessions and will continue to.”

Late-breaking science

The LBS sessions kick off at 9:30 a.m. ET Saturday with AVATAR, a randomized trial of aortic valve replacement vs. watchful waiting in severe aortic stenosis proved asymptomatic through exercise testing.

“The findings of that trial, depending on what they are, could certainly impact clinical practice because it’s a very common scenario in which we have elderly patients with aortic valve stenosis that might be severe but they may not be symptomatic,” he said.

It’s followed by a randomized trial from the Cardiothoracic Surgical Trials Network, examining whether tricuspid repair at the time of mitral valve surgery leads to beneficial outcomes. “I think it’s a pretty important study,” Dr. Patel said, “because it’ll again affect how we think about our clinical practice.”

Rounding out the LBS.01 session is RAPID CABG, comparing early vs. delayed coronary bypass graft surgery (CABG) in patients with acute coronary syndromes on ticagrelor, and the pivotal U.S. VEST trial of an external support device already approved in Europe for saphenous vein grafts during CABG.

Saturday’s LBS.02 at 3:00 p.m. ET is devoted to hypertension and looks at how the COVID-19 pandemic affected blood pressure control. There’s also a study of remotely delivered hypertension and lipid management in 10,000 patients across the Partners Healthcare System and a cluster randomized trial of a village doctor–led blood pressure intervention in rural China.

Sunday’s LBS.03 at 8:00 a.m. ET is focused on atrial arrhythmias, starting with the CRAVE trial examining the effect of caffeine consumption on cardiac ectopy burden in 108 patients using an N-of-1 design and 2-day blocks on and off caffeine. “There’s an ability to identify a dose response that you get arrhythmias when you increase the amount of coffee you drink vs. not in an individual, so I think that will be likely discussed a lot and worth paying attention to,” Dr. Patel said.

The session also includes GIRAF, a comparison of cognitive outcomes with dabigatran (Pradaxa) vs. warfarin (Coumadin) in nonvalvular atrial fibrillation (AF); PALACS, a randomized trial examining whether left-sided pericardiotomy prevents AF after cardiac surgery; and AMAZE, which study sponsor AtriCure revealed missed its primary efficacy endpoint of freedom from AF with the LARIAT suture delivery device for left atrial appendage closure plus pulmonary vein isolation.

LBS.04 at 3:30 p.m. ET Sunday takes on digital health, with results from the nonrandomized Fitbit Heart Study on AF notifications from 450,000 participants wearing a single-lead ECG patch. “A lot of technologies claim that they can detect things, and we should ask that people go through the rigorous evaluation to see if they in fact do. So, in that respect, I think it›s an important step,” observed Dr. Patel.

Also on tap is I-STOP-AFib, another N-of-1 study using mobile apps and the AliveCor device to identify individual AF triggers; and REVeAL-HF, a 4,000-patient study examining whether electronic alerts that provide clinicians with prognostic information on their heart failure (HF) patients will reduce mortality and 30-day HF hospitalizations.

LBS.05 at 5:00 p.m. ET provides new information from EMPEROR-Preserved in HF with preserved ejection fraction and main results from EMPULSE, also using the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in 530 patients hospitalized for acute HF.

The session also features CHIEF-HF, a randomized trial leveraging mobile technologies to test whether 12 weeks of another SGLT2 inhibitor, canagliflozin (Invokana), is superior to placebo for improving HF symptoms; and DREAM-HF, a comparison of transendocardial delivery of allogeneic mesenchymal precursor cells vs. a sham comparator in chronic HF as a result of left ventricular systolic dysfunction.

Monday’s LBS.06 at 8:00 a.m. ET details the safety and cholesterol-lowering efficacy of MK-0616, an investigational oral PCSK9 inhibitor. “It’s just a phase 2 [trial], but there’s interest in an oral PCSK9 inhibitor, given that the current ones are subcutaneous,” Dr. Patel said.

Results will also be presented from PREPARE-IT 2, which tested icosapent ethyl vs. placebo in outpatients with COVID-19. In the recently reported PREPARE-IT 1, a loading dose of icosapent ethyl failed to reduce the risk of hospitalization with SARS-CoV-2 infection among at-risk individuals.

LBS.07 at 11:00 a.m. Monday completes the late-breakers with new results from ASCEND, this time examining the effect of aspirin on dementia and cognitive impairment in patients with diabetes.

Next up is a look at the effectiveness of P2Y12 inhibitors in hospitalized patients with COVID-19 in the adaptive ACTIV-4a trial, followed by results of the pivotal phase 3 REVERSE-IT trial of bentracimab, a recombinant human monoclonal antibody antigen fragment designed to reverse the antiplatelet activity of ticagrelor in the event of major bleeding or when urgent surgery is needed.

Closing out the session is AXIOMATIC-TKR, a double-blind comparison of the safety and efficacy of the investigational oral factor XI anticoagulant JNJ-70033093 vs. subcutaneous enoxaparin (Lovenox) in elective total knee replacement.

For those searching for more AHA-related science online, the Resuscitation Science Symposium (ReSS) will run from this Friday through Sunday and the Quality of Care and Outcomes Research (QCOR) Scientific Sessions will take the stage next Monday, Nov. 15.

A version of this article first appeared on Medscape.com.

Virtual platforms democratized scientific meetings during the COVID-19 pandemic but, as any meeting-goer will tell you, it’s the questions from the floor and the back-and-forth of an expert panel that often reveal the importance of and/or problems with a presentation. It’s the scrutiny that makes the science resonate, especially in this postfactual era.

The all-virtual American Heart Association Scientific Sessions 2021 is looking to recreate the engagement of an in-person meeting by offering more live interactive events. They range from seven late-breaking science (LBS) sessions to Saturday’s fireside chat on the Pfizer and Moderna COVID-19 vaccines and Monday’s dive into the controversial new AHA/American College of Cardiology Chest Pain guidelines.

To help digest the latest science, attendees will be able to have their questions answered in real-time via Slido, meet with the trialists, and hear live commentary from key opinion leaders after the live events. A networking function will also allow attendees and exhibitors to chat or meet virtually.

“In this day and age, many people pretty quickly can get access to the science but it’s what I call the IC sort of phenomenon – the presentation of the information, the context of the information, putting it into how I’m going to use it in my practice, and then the critical appraisal – that’s what most people want at the Scientific Sessions,” program committee chair Manesh R. Patel, MD, of Duke University School of Medicine, said in an interview. “We’re all craving ways in which we can interact with one another to put things in context.”

Plans for a hybrid in-person meeting in Boston were scuttled in September because of the Delta variant surge, but the theme of the meeting remained: “One World. Together for Science.” Attendees will be able to access more than 500 live and on-demand sessions including 117 oral abstracts, 286 poster sessions, 59 moderated digital posters, and over a dozen sessions focused on strategies to promote health equity.

“Last year there was a Presidential Session and a statement on structural racism, so we wanted to take the next step and say, What are the ways in which people are starting to interact and do things to make a difference?” explained Dr. Patel. “So, this year, you’ll see different versions of that from the Main Event session, which has some case vignettes and a panel discussion, to other health equity sessions that describe not just COVID care, but blood pressure care, maternal-fetal medicine, and congenital kids. Wherever we can, we’ve tried to infuse it throughout the sessions and will continue to.”

Late-breaking science

The LBS sessions kick off at 9:30 a.m. ET Saturday with AVATAR, a randomized trial of aortic valve replacement vs. watchful waiting in severe aortic stenosis proved asymptomatic through exercise testing.

“The findings of that trial, depending on what they are, could certainly impact clinical practice because it’s a very common scenario in which we have elderly patients with aortic valve stenosis that might be severe but they may not be symptomatic,” he said.

It’s followed by a randomized trial from the Cardiothoracic Surgical Trials Network, examining whether tricuspid repair at the time of mitral valve surgery leads to beneficial outcomes. “I think it’s a pretty important study,” Dr. Patel said, “because it’ll again affect how we think about our clinical practice.”

Rounding out the LBS.01 session is RAPID CABG, comparing early vs. delayed coronary bypass graft surgery (CABG) in patients with acute coronary syndromes on ticagrelor, and the pivotal U.S. VEST trial of an external support device already approved in Europe for saphenous vein grafts during CABG.

Saturday’s LBS.02 at 3:00 p.m. ET is devoted to hypertension and looks at how the COVID-19 pandemic affected blood pressure control. There’s also a study of remotely delivered hypertension and lipid management in 10,000 patients across the Partners Healthcare System and a cluster randomized trial of a village doctor–led blood pressure intervention in rural China.

Sunday’s LBS.03 at 8:00 a.m. ET is focused on atrial arrhythmias, starting with the CRAVE trial examining the effect of caffeine consumption on cardiac ectopy burden in 108 patients using an N-of-1 design and 2-day blocks on and off caffeine. “There’s an ability to identify a dose response that you get arrhythmias when you increase the amount of coffee you drink vs. not in an individual, so I think that will be likely discussed a lot and worth paying attention to,” Dr. Patel said.

The session also includes GIRAF, a comparison of cognitive outcomes with dabigatran (Pradaxa) vs. warfarin (Coumadin) in nonvalvular atrial fibrillation (AF); PALACS, a randomized trial examining whether left-sided pericardiotomy prevents AF after cardiac surgery; and AMAZE, which study sponsor AtriCure revealed missed its primary efficacy endpoint of freedom from AF with the LARIAT suture delivery device for left atrial appendage closure plus pulmonary vein isolation.

LBS.04 at 3:30 p.m. ET Sunday takes on digital health, with results from the nonrandomized Fitbit Heart Study on AF notifications from 450,000 participants wearing a single-lead ECG patch. “A lot of technologies claim that they can detect things, and we should ask that people go through the rigorous evaluation to see if they in fact do. So, in that respect, I think it›s an important step,” observed Dr. Patel.

Also on tap is I-STOP-AFib, another N-of-1 study using mobile apps and the AliveCor device to identify individual AF triggers; and REVeAL-HF, a 4,000-patient study examining whether electronic alerts that provide clinicians with prognostic information on their heart failure (HF) patients will reduce mortality and 30-day HF hospitalizations.

LBS.05 at 5:00 p.m. ET provides new information from EMPEROR-Preserved in HF with preserved ejection fraction and main results from EMPULSE, also using the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in 530 patients hospitalized for acute HF.

The session also features CHIEF-HF, a randomized trial leveraging mobile technologies to test whether 12 weeks of another SGLT2 inhibitor, canagliflozin (Invokana), is superior to placebo for improving HF symptoms; and DREAM-HF, a comparison of transendocardial delivery of allogeneic mesenchymal precursor cells vs. a sham comparator in chronic HF as a result of left ventricular systolic dysfunction.

Monday’s LBS.06 at 8:00 a.m. ET details the safety and cholesterol-lowering efficacy of MK-0616, an investigational oral PCSK9 inhibitor. “It’s just a phase 2 [trial], but there’s interest in an oral PCSK9 inhibitor, given that the current ones are subcutaneous,” Dr. Patel said.

Results will also be presented from PREPARE-IT 2, which tested icosapent ethyl vs. placebo in outpatients with COVID-19. In the recently reported PREPARE-IT 1, a loading dose of icosapent ethyl failed to reduce the risk of hospitalization with SARS-CoV-2 infection among at-risk individuals.

LBS.07 at 11:00 a.m. Monday completes the late-breakers with new results from ASCEND, this time examining the effect of aspirin on dementia and cognitive impairment in patients with diabetes.

Next up is a look at the effectiveness of P2Y12 inhibitors in hospitalized patients with COVID-19 in the adaptive ACTIV-4a trial, followed by results of the pivotal phase 3 REVERSE-IT trial of bentracimab, a recombinant human monoclonal antibody antigen fragment designed to reverse the antiplatelet activity of ticagrelor in the event of major bleeding or when urgent surgery is needed.

Closing out the session is AXIOMATIC-TKR, a double-blind comparison of the safety and efficacy of the investigational oral factor XI anticoagulant JNJ-70033093 vs. subcutaneous enoxaparin (Lovenox) in elective total knee replacement.

For those searching for more AHA-related science online, the Resuscitation Science Symposium (ReSS) will run from this Friday through Sunday and the Quality of Care and Outcomes Research (QCOR) Scientific Sessions will take the stage next Monday, Nov. 15.

A version of this article first appeared on Medscape.com.

The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.

“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.

When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.

These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).

In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
 

No differences seen across outcomes

When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).

Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.

At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.

“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.

While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
 

Patient discomfort is greater with FFR

Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.

Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.

Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.

The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.

Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.

For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.

However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.

Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.

The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.

“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.

When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.

These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).

In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
 

No differences seen across outcomes

When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).

Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.

At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.

“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.

While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
 

Patient discomfort is greater with FFR

Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.

Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.

Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.

The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.

Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.

For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.

However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.

Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.

The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.

“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.

When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.

These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).

In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
 

No differences seen across outcomes

When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).

Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.

At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.

“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.

While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
 

Patient discomfort is greater with FFR

Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.

Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.

Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.

The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.

Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.

For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.

However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.

Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.

Coronary stenting guided by fractional flow reserve (FFR) readings, considered to reflect the targeted lesion’s functional impact, was no match for coronary bypass surgery (CABG) in patients with multivessel disease (MVD) in a major international randomized trial.

M. Alexander Otto/MDedge News

Indeed, FFR-guided percutaneous coronary intervention (PCI) using one of the latest drug-eluting stents (DES) seemed to perform poorly in the trial, compared with surgery, apparently upping the risk for clinical events by 50% over 1 year.

Designed statistically for noninferiority, the third Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME 3) trial, with 1,500 randomized patients, showed that FFR-guided PCI was “not noninferior” to CABG. Of those randomized to PCI, 10.6% met the 1-year primary endpoint of major adverse cardiac or cerebrovascular events (MACCE), compared with only 6.9% of patients assigned to CABG.

The trial enrolled only patients with three-vessel coronary disease with no left-main coronary artery involvement, who were declared by their institution’s multidisciplinary heart team to be appropriate for either form of revascularization.

One of the roles of FFR for PCI guidance is to identify significant lesions “that are underrecognized by the angiogram,” which is less likely to happen in patients with very complex coronary anatomy, study chair William F. Fearon, MD, Stanford (Calif.) University, said in an interview.

“That’s what we saw in a subgroup analysis based on SYNTAX score,” an index of lesion complexity. “In patients with very high SYNTAX scores, CABG outperformed FFR-guided PCI. But if you look at patients with low SYNTAX scores, actually, FFR-guided PCI outperformed CABG for 1-year MACCE.”

Dr. Fearon is lead author on the study’s Nov. 4, 2021, publication in the New England Journal of Medicine, its release timed to coincide with his presentation of the trial at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.

He noted that FAME-3 “wasn’t designed or powered to test for superiority,” so its results do not imply CABG is superior to FFR-PCI in patients with MVD, and remains “inconclusive” on that question.

“I think what this study does is provide both the physician and patients more contemporary data and information on options and expected outcomes in multivessel disease. So if you are a patient who has less complex disease, I think you can feel comfortable that you will get an equivalent result with FFR-guided PCI.” But, at least based on FAME-3, Dr. Fearon said, CABG provides better outcomes in patients with more complex disease.

“I think there are still patients that look at trade-offs. Some patients will accept a higher event rate in order to avoid a long recovery, and vice versa.” So the trial may allow patients and physicians to make more informed decisions, he said.

A main message of FAME-3 “is that we’re getting very good results with three-vessel PCI, but better results with surgery,” Ran Kornowski, MD, Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, said as a discussant following Dr. Fearon’s presentation of the trial. The subanalysis by SYNTAX score, he agreed, probably could be used as part of shared decision-making with patients.

Not all that surprising

“It’s a well-designed study, with a lot of patients,” said surgeon Frank W. Sellke, MD, of Rhode Island Hospital, Miriam Hospital, and Brown University, all in Providence.

“I don’t think it’s all that surprising,” he said in an interview. “It’s very consistent with what other studies have shown, that for three-vessel disease, surgery tends to have the edge,” even when pitted against FFR-guided PCI.

Indeed, pressure-wire FFR-PCI has a spotty history, even as an alternative to standard angiography-based PCI. For example, it has performed well in registry and other cohort studies but showed no advantage in the all-comers RIPCORD-2 trial or in the setting of complete revascularization PCI for acute MI in FLOWER-MI. And it emitted an increased-mortality signal in the prematurely halted FUTURE trial.

In FAME-3, “the 1-year follow-up was the best chance for FFR-PCI to be noninferior to CABG. The CABG advantage is only going to get better with time if prior experience and pathobiology is true,” Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

Overall, “the quality and quantity of evidence is insufficient to support FFR-guided PCI” in patients with complex coronary artery disease (CAD), he said. “I would also argue that the evidence for FFR-guided PCI for simple CAD is also not high quality.”

Dr. Kaul also blasted the claim that FFR-PCI was seen to perform better against CABG in patients with low SYNTAX scores. “In general, one cannot use a positive subgroup in a null or negative trial, as is the case with FAME-3, to ‘rescue’ the treatment intervention.” Such a positive subgroup finding, he said, “would at best be deemed hypothesis-generating and not hypothesis validating.”

Dr. Fearon agreed that the subgroup analysis by SYNTAX score, though prespecified, was only hypothesis generating. “But I think that other studies have shown the same thing – that in less complex disease, the two strategies appear to perform in a similar fashion.”

The FAME-3 trial’s 1,500 patients were randomly assigned at 48 centers to undergo standard CABG or FFR-guided PCI with Resolute Integrity (Medtronic) zotarolimus-eluting DES. Lesions with a pressure-wire FFR of 0.80 or less were stented and those with higher FFR readings were deferred.

The 1-year hazard ratio for the primary endpoint—a composite of death from any cause, MI, stroke, or repeat revascularization – was 1.5 (95% confidence interval, 1.1-2.2) with a noninferiority P value of .35 for the comparison of FFR-PCI versus CABG.

FFR-guided PCI fared significantly better than CABG for some safety endpoints, including major bleeding (1.6% vs 3.8%, P < .01), arrhythmia including atrial fibrillation (2.4% vs. 14.1%, P < .001), acute kidney injury (0.1% vs 0.9%, P < .04), and 30-day rehospitalization (5.5% vs 10.2%, P < .001).
 

Did the primary endpoint favor CABG?

At a media briefing prior to Dr. Fearon’s TCT 2021 presentation of the trail, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, proposed that the inclusion of repeat revascularization in the trial’s composite primary endpoint tilted the outcome in favor of CABG. “To me, the FAME-3 results are predictable because repeat revascularization is in the equation.”

M. Alexander Otto, MDedge News

It’s well recognized that the endpoint is less likely after CABG than PCI. The latter treats focal lesions that are a limited part of a coronary artery in which CAD is still likely progressing. CABG, on the other hand, can bypass longer segments of diseased artery.

Indeed, as Dr. Fearon reported, the rates of death, MI, or stroke excluding repeat revascularization were 7.3% with FFR-PCI and 5.2% for CABG, for an HR of 1.4 (95% CI, 0.9-2.1).

Dr. Mehran also proposed that intravascular-ultrasound (IVUS) guidance, had it been part of the trial, could potentially have boosted the performance of FFR-PCI.

Repeat revascularization, Dr. Kaul agreed, “should not have been included” in the trial’s primary endpoint. It had been added “to amplify events and to minimize sample size. Not including revascularization would render the sample size prohibitive. There is always give and take in designing clinical trials.”

And he agreed that “IVUS-based PCI optimization would have further improved PCI outcomes.” However, “IVUS plus FFR adds to the procedural burden and limited resources available.” Dr. Fearon said when interviewed that the trial’s definition of procedural MI, a component of the primary endpoint, might potentially be seen as controversial. Procedural MIs in both the PCI and CABG groups were required to meet the standards of CABG-related type-5 MI according to the third and fourth Universal Definitions. The had also had to be accompanied by “a significant finding like new Q waves or a new wall-motion abnormality on echocardiography,” he said.

“That’s fairly strict. Because of that, we had a low rate of periprocedural MI and it was similar between the two groups, around 1.5% in both arms.”

FAME-3 was funded by Medtronic and Abbott Vascular. Dr. Kaul disclosed no relevant financial relationships. Dr. Kornowsky receives royalties from or holds intellectual property rights with CathWorks. Dr. Mehran disclosed financial ties to numerous pharmaceutical and device companies, and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.

A version of this article first appeared on Medscape.com.

Coronary stenting guided by fractional flow reserve (FFR) readings, considered to reflect the targeted lesion’s functional impact, was no match for coronary bypass surgery (CABG) in patients with multivessel disease (MVD) in a major international randomized trial.

M. Alexander Otto/MDedge News

Indeed, FFR-guided percutaneous coronary intervention (PCI) using one of the latest drug-eluting stents (DES) seemed to perform poorly in the trial, compared with surgery, apparently upping the risk for clinical events by 50% over 1 year.

Designed statistically for noninferiority, the third Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME 3) trial, with 1,500 randomized patients, showed that FFR-guided PCI was “not noninferior” to CABG. Of those randomized to PCI, 10.6% met the 1-year primary endpoint of major adverse cardiac or cerebrovascular events (MACCE), compared with only 6.9% of patients assigned to CABG.

The trial enrolled only patients with three-vessel coronary disease with no left-main coronary artery involvement, who were declared by their institution’s multidisciplinary heart team to be appropriate for either form of revascularization.

One of the roles of FFR for PCI guidance is to identify significant lesions “that are underrecognized by the angiogram,” which is less likely to happen in patients with very complex coronary anatomy, study chair William F. Fearon, MD, Stanford (Calif.) University, said in an interview.

“That’s what we saw in a subgroup analysis based on SYNTAX score,” an index of lesion complexity. “In patients with very high SYNTAX scores, CABG outperformed FFR-guided PCI. But if you look at patients with low SYNTAX scores, actually, FFR-guided PCI outperformed CABG for 1-year MACCE.”

Dr. Fearon is lead author on the study’s Nov. 4, 2021, publication in the New England Journal of Medicine, its release timed to coincide with his presentation of the trial at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.

He noted that FAME-3 “wasn’t designed or powered to test for superiority,” so its results do not imply CABG is superior to FFR-PCI in patients with MVD, and remains “inconclusive” on that question.

“I think what this study does is provide both the physician and patients more contemporary data and information on options and expected outcomes in multivessel disease. So if you are a patient who has less complex disease, I think you can feel comfortable that you will get an equivalent result with FFR-guided PCI.” But, at least based on FAME-3, Dr. Fearon said, CABG provides better outcomes in patients with more complex disease.

“I think there are still patients that look at trade-offs. Some patients will accept a higher event rate in order to avoid a long recovery, and vice versa.” So the trial may allow patients and physicians to make more informed decisions, he said.

A main message of FAME-3 “is that we’re getting very good results with three-vessel PCI, but better results with surgery,” Ran Kornowski, MD, Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, said as a discussant following Dr. Fearon’s presentation of the trial. The subanalysis by SYNTAX score, he agreed, probably could be used as part of shared decision-making with patients.

Not all that surprising

“It’s a well-designed study, with a lot of patients,” said surgeon Frank W. Sellke, MD, of Rhode Island Hospital, Miriam Hospital, and Brown University, all in Providence.

“I don’t think it’s all that surprising,” he said in an interview. “It’s very consistent with what other studies have shown, that for three-vessel disease, surgery tends to have the edge,” even when pitted against FFR-guided PCI.

Indeed, pressure-wire FFR-PCI has a spotty history, even as an alternative to standard angiography-based PCI. For example, it has performed well in registry and other cohort studies but showed no advantage in the all-comers RIPCORD-2 trial or in the setting of complete revascularization PCI for acute MI in FLOWER-MI. And it emitted an increased-mortality signal in the prematurely halted FUTURE trial.

In FAME-3, “the 1-year follow-up was the best chance for FFR-PCI to be noninferior to CABG. The CABG advantage is only going to get better with time if prior experience and pathobiology is true,” Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

Overall, “the quality and quantity of evidence is insufficient to support FFR-guided PCI” in patients with complex coronary artery disease (CAD), he said. “I would also argue that the evidence for FFR-guided PCI for simple CAD is also not high quality.”

Dr. Kaul also blasted the claim that FFR-PCI was seen to perform better against CABG in patients with low SYNTAX scores. “In general, one cannot use a positive subgroup in a null or negative trial, as is the case with FAME-3, to ‘rescue’ the treatment intervention.” Such a positive subgroup finding, he said, “would at best be deemed hypothesis-generating and not hypothesis validating.”

Dr. Fearon agreed that the subgroup analysis by SYNTAX score, though prespecified, was only hypothesis generating. “But I think that other studies have shown the same thing – that in less complex disease, the two strategies appear to perform in a similar fashion.”

The FAME-3 trial’s 1,500 patients were randomly assigned at 48 centers to undergo standard CABG or FFR-guided PCI with Resolute Integrity (Medtronic) zotarolimus-eluting DES. Lesions with a pressure-wire FFR of 0.80 or less were stented and those with higher FFR readings were deferred.

The 1-year hazard ratio for the primary endpoint—a composite of death from any cause, MI, stroke, or repeat revascularization – was 1.5 (95% confidence interval, 1.1-2.2) with a noninferiority P value of .35 for the comparison of FFR-PCI versus CABG.

FFR-guided PCI fared significantly better than CABG for some safety endpoints, including major bleeding (1.6% vs 3.8%, P < .01), arrhythmia including atrial fibrillation (2.4% vs. 14.1%, P < .001), acute kidney injury (0.1% vs 0.9%, P < .04), and 30-day rehospitalization (5.5% vs 10.2%, P < .001).
 

Did the primary endpoint favor CABG?

At a media briefing prior to Dr. Fearon’s TCT 2021 presentation of the trail, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, proposed that the inclusion of repeat revascularization in the trial’s composite primary endpoint tilted the outcome in favor of CABG. “To me, the FAME-3 results are predictable because repeat revascularization is in the equation.”

M. Alexander Otto, MDedge News

It’s well recognized that the endpoint is less likely after CABG than PCI. The latter treats focal lesions that are a limited part of a coronary artery in which CAD is still likely progressing. CABG, on the other hand, can bypass longer segments of diseased artery.

Indeed, as Dr. Fearon reported, the rates of death, MI, or stroke excluding repeat revascularization were 7.3% with FFR-PCI and 5.2% for CABG, for an HR of 1.4 (95% CI, 0.9-2.1).

Dr. Mehran also proposed that intravascular-ultrasound (IVUS) guidance, had it been part of the trial, could potentially have boosted the performance of FFR-PCI.

Repeat revascularization, Dr. Kaul agreed, “should not have been included” in the trial’s primary endpoint. It had been added “to amplify events and to minimize sample size. Not including revascularization would render the sample size prohibitive. There is always give and take in designing clinical trials.”

And he agreed that “IVUS-based PCI optimization would have further improved PCI outcomes.” However, “IVUS plus FFR adds to the procedural burden and limited resources available.” Dr. Fearon said when interviewed that the trial’s definition of procedural MI, a component of the primary endpoint, might potentially be seen as controversial. Procedural MIs in both the PCI and CABG groups were required to meet the standards of CABG-related type-5 MI according to the third and fourth Universal Definitions. The had also had to be accompanied by “a significant finding like new Q waves or a new wall-motion abnormality on echocardiography,” he said.

“That’s fairly strict. Because of that, we had a low rate of periprocedural MI and it was similar between the two groups, around 1.5% in both arms.”

FAME-3 was funded by Medtronic and Abbott Vascular. Dr. Kaul disclosed no relevant financial relationships. Dr. Kornowsky receives royalties from or holds intellectual property rights with CathWorks. Dr. Mehran disclosed financial ties to numerous pharmaceutical and device companies, and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.

A version of this article first appeared on Medscape.com.

Coronary stenting guided by fractional flow reserve (FFR) readings, considered to reflect the targeted lesion’s functional impact, was no match for coronary bypass surgery (CABG) in patients with multivessel disease (MVD) in a major international randomized trial.

M. Alexander Otto/MDedge News

Indeed, FFR-guided percutaneous coronary intervention (PCI) using one of the latest drug-eluting stents (DES) seemed to perform poorly in the trial, compared with surgery, apparently upping the risk for clinical events by 50% over 1 year.

Designed statistically for noninferiority, the third Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME 3) trial, with 1,500 randomized patients, showed that FFR-guided PCI was “not noninferior” to CABG. Of those randomized to PCI, 10.6% met the 1-year primary endpoint of major adverse cardiac or cerebrovascular events (MACCE), compared with only 6.9% of patients assigned to CABG.

The trial enrolled only patients with three-vessel coronary disease with no left-main coronary artery involvement, who were declared by their institution’s multidisciplinary heart team to be appropriate for either form of revascularization.

One of the roles of FFR for PCI guidance is to identify significant lesions “that are underrecognized by the angiogram,” which is less likely to happen in patients with very complex coronary anatomy, study chair William F. Fearon, MD, Stanford (Calif.) University, said in an interview.

“That’s what we saw in a subgroup analysis based on SYNTAX score,” an index of lesion complexity. “In patients with very high SYNTAX scores, CABG outperformed FFR-guided PCI. But if you look at patients with low SYNTAX scores, actually, FFR-guided PCI outperformed CABG for 1-year MACCE.”

Dr. Fearon is lead author on the study’s Nov. 4, 2021, publication in the New England Journal of Medicine, its release timed to coincide with his presentation of the trial at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.

He noted that FAME-3 “wasn’t designed or powered to test for superiority,” so its results do not imply CABG is superior to FFR-PCI in patients with MVD, and remains “inconclusive” on that question.

“I think what this study does is provide both the physician and patients more contemporary data and information on options and expected outcomes in multivessel disease. So if you are a patient who has less complex disease, I think you can feel comfortable that you will get an equivalent result with FFR-guided PCI.” But, at least based on FAME-3, Dr. Fearon said, CABG provides better outcomes in patients with more complex disease.

“I think there are still patients that look at trade-offs. Some patients will accept a higher event rate in order to avoid a long recovery, and vice versa.” So the trial may allow patients and physicians to make more informed decisions, he said.

A main message of FAME-3 “is that we’re getting very good results with three-vessel PCI, but better results with surgery,” Ran Kornowski, MD, Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, said as a discussant following Dr. Fearon’s presentation of the trial. The subanalysis by SYNTAX score, he agreed, probably could be used as part of shared decision-making with patients.

Not all that surprising

“It’s a well-designed study, with a lot of patients,” said surgeon Frank W. Sellke, MD, of Rhode Island Hospital, Miriam Hospital, and Brown University, all in Providence.

“I don’t think it’s all that surprising,” he said in an interview. “It’s very consistent with what other studies have shown, that for three-vessel disease, surgery tends to have the edge,” even when pitted against FFR-guided PCI.

Indeed, pressure-wire FFR-PCI has a spotty history, even as an alternative to standard angiography-based PCI. For example, it has performed well in registry and other cohort studies but showed no advantage in the all-comers RIPCORD-2 trial or in the setting of complete revascularization PCI for acute MI in FLOWER-MI. And it emitted an increased-mortality signal in the prematurely halted FUTURE trial.

In FAME-3, “the 1-year follow-up was the best chance for FFR-PCI to be noninferior to CABG. The CABG advantage is only going to get better with time if prior experience and pathobiology is true,” Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

Overall, “the quality and quantity of evidence is insufficient to support FFR-guided PCI” in patients with complex coronary artery disease (CAD), he said. “I would also argue that the evidence for FFR-guided PCI for simple CAD is also not high quality.”

Dr. Kaul also blasted the claim that FFR-PCI was seen to perform better against CABG in patients with low SYNTAX scores. “In general, one cannot use a positive subgroup in a null or negative trial, as is the case with FAME-3, to ‘rescue’ the treatment intervention.” Such a positive subgroup finding, he said, “would at best be deemed hypothesis-generating and not hypothesis validating.”

Dr. Fearon agreed that the subgroup analysis by SYNTAX score, though prespecified, was only hypothesis generating. “But I think that other studies have shown the same thing – that in less complex disease, the two strategies appear to perform in a similar fashion.”

The FAME-3 trial’s 1,500 patients were randomly assigned at 48 centers to undergo standard CABG or FFR-guided PCI with Resolute Integrity (Medtronic) zotarolimus-eluting DES. Lesions with a pressure-wire FFR of 0.80 or less were stented and those with higher FFR readings were deferred.

The 1-year hazard ratio for the primary endpoint—a composite of death from any cause, MI, stroke, or repeat revascularization – was 1.5 (95% confidence interval, 1.1-2.2) with a noninferiority P value of .35 for the comparison of FFR-PCI versus CABG.

FFR-guided PCI fared significantly better than CABG for some safety endpoints, including major bleeding (1.6% vs 3.8%, P < .01), arrhythmia including atrial fibrillation (2.4% vs. 14.1%, P < .001), acute kidney injury (0.1% vs 0.9%, P < .04), and 30-day rehospitalization (5.5% vs 10.2%, P < .001).
 

Did the primary endpoint favor CABG?

At a media briefing prior to Dr. Fearon’s TCT 2021 presentation of the trail, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, proposed that the inclusion of repeat revascularization in the trial’s composite primary endpoint tilted the outcome in favor of CABG. “To me, the FAME-3 results are predictable because repeat revascularization is in the equation.”

M. Alexander Otto, MDedge News

It’s well recognized that the endpoint is less likely after CABG than PCI. The latter treats focal lesions that are a limited part of a coronary artery in which CAD is still likely progressing. CABG, on the other hand, can bypass longer segments of diseased artery.

Indeed, as Dr. Fearon reported, the rates of death, MI, or stroke excluding repeat revascularization were 7.3% with FFR-PCI and 5.2% for CABG, for an HR of 1.4 (95% CI, 0.9-2.1).

Dr. Mehran also proposed that intravascular-ultrasound (IVUS) guidance, had it been part of the trial, could potentially have boosted the performance of FFR-PCI.

Repeat revascularization, Dr. Kaul agreed, “should not have been included” in the trial’s primary endpoint. It had been added “to amplify events and to minimize sample size. Not including revascularization would render the sample size prohibitive. There is always give and take in designing clinical trials.”

And he agreed that “IVUS-based PCI optimization would have further improved PCI outcomes.” However, “IVUS plus FFR adds to the procedural burden and limited resources available.” Dr. Fearon said when interviewed that the trial’s definition of procedural MI, a component of the primary endpoint, might potentially be seen as controversial. Procedural MIs in both the PCI and CABG groups were required to meet the standards of CABG-related type-5 MI according to the third and fourth Universal Definitions. The had also had to be accompanied by “a significant finding like new Q waves or a new wall-motion abnormality on echocardiography,” he said.

“That’s fairly strict. Because of that, we had a low rate of periprocedural MI and it was similar between the two groups, around 1.5% in both arms.”

FAME-3 was funded by Medtronic and Abbott Vascular. Dr. Kaul disclosed no relevant financial relationships. Dr. Kornowsky receives royalties from or holds intellectual property rights with CathWorks. Dr. Mehran disclosed financial ties to numerous pharmaceutical and device companies, and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.

A version of this article first appeared on Medscape.com.

It was Oct. 28 when the two big North American cardiology societies issued a joint practice guideline on evaluating and managing chest pain that was endorsed by five other subspecialty groups. The next day, another group that had taken part in the document’s genesis explained why it wasn’t one of those five.

Although the American Society of Nuclear Cardiology (ASNC) was “actively engaged at every stage of the guideline-writing and review process,” the society “could not endorse the guideline,” the society announced in a statement released to clinicians and the media. The most prominent cited reason: It doesn’t adequately “support the principle of Patient First Imaging.”

The guideline was published in Circulation and the Journal of the American College of Cardiology, flagship journals of the American Heart Association and American College of Cardiology, respectively.

The document notes at least two clinicians represented ASNC as peer reviewers, and another was on the writing committee, but the organization does not appear in the list of societies endorsing the document.

“We believe that the document fails to provide unbiased guidance to health care professionals on the optimal evaluation of patients with chest pain,” contends an editorial ASNC board members have scheduled for the Jan. 10 issue of the Journal of Nuclear Medicine but is available now on an open-access preprint server.

“Despite the many important and helpful recommendations in the new guideline, there are several recommendations that we could not support,” it states.

“The ASNC board of directors reviewed the document twice during the endorsement process,” and the society “offered substantive comments after the first endorsement review, several of which were addressed,” Randall C. Thompson, MD, St. Luke’s Mid America Heart Institute and University of Missouri–Kansas City, said in an interview.

“However, some of the board’s concerns went unresolved. It was after the board’s second review, when the document had been declared finalized, that they voted not to endorse,” said Dr. Thompson, who is ASNC president.

“When we gather multiple organizations together to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of peer-reviewed, published literature and create clinical practice recommendations,” Guideline Writing Committee Chair Martha Gulati, MD, University of Arizona, Phoenix, told this news organization in a prepared statement.

“The ASNC had a representative on the writing committee who is a coauthor on the paper and actively participated throughout the writing process the past 4 years,” she said. “The final guideline reflects the latest evidence-based recommendations for the evaluation and diagnosis of chest pain, as agreed by the seven endorsing organizations.”

The document does not clearly note that an ASNC representative was on the writing committee. However, ASNC confirmed that Renee Bullock-Palmer, MD, Deborah Heart and Lung Center, Browns Mills, N.J., is a fellow of the ASNC and had represented the group as one of the coauthors. Two “official reviewers” of the document, however, are listed as ASNC representatives.
 

Points of contention

“The decision about which test to order can be a nuanced one, and cardiac imaging tests tend to be complementary,” elaborates the editorial on the issue of patient-centered management.

Careful patient selection for different tests is important, “and physician and technical local expertise, availability, quality of equipment, and patient preference are extremely important factors to consider. There is not enough emphasis on this important point,” contend the authors. “This is an important limitation of the guideline.”

Other issues of concern include “lack of balance in the document’s presentation of the science on FFR-CT [fractional flow reserve assessment with computed tomography] and its inappropriately prominent endorsement,” the editorial states.

The U.S. Food and Drug Administration–recognized “limitations and contraindications” to FFR-CT tend to be glossed over in the document, Dr. Thompson said. And most ASNC board members were “concerned with the prominent location of the recommendations for FFR-CT in various tables – especially since there was minimal-to-no discussion of the fact that it is currently provided by only one company, that it is not widely available nor covered routinely by health insurance carriers, and [that] the accuracy in the most relevant population is disputed.”

In other concerns, the document “inadequately discusses the benefit” of combining coronary artery calcium (CAC) scores with functional testing, which ASNC said it supports. For example, adding CAC scores to myocardial perfusion imaging improves its diagnostic accuracy and prognostic power.
 

Functional vs. anatomic testing?

Moreover, “it is no longer appropriate to bundle all types of stress testing together. All stress imaging tests have their unique advantages and limitations.” Yet, “the concept of the dichotomy of functional testing versus anatomic testing is a common theme in the guideline in many important patient groups,” the editorial states. That could overemphasize CT angiography and thus “blur distinction between different types of functional tests.”

Such concerns about “imbalance” in the portrayals of the two kinds of tests were “amplified by the problem of health insurance companies and radiologic benefits managers inappropriately substituting a test that was ordered by a physician with a different test,” Dr. Thompson elaborated. “There is the impression that some of them ‘cherry-pick’ certain guidelines and that this practice is harmful to patients.”

The ASNC currently does not plan its own corresponding guideline, he said. But the editorial says that “over the coming weeks and months ASNC will offer a series of webinars and other programs that address specific patient populations and dilemmas.” Also, “we will enhance our focus on programs to address quality and efficiency to support a patient-first approach to imaging.”

The five subspecialty groups that have endorsed the document are the American Society of Echocardiography, American College of Chest Physicians, Society for Academic Emergency Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance.

Dr. Thompson has reported no relevant financial relationships. Statements of disclosure for the other editorial writers are listed in the publication.

A version of this article first appeared on Medscape.com.

It was Oct. 28 when the two big North American cardiology societies issued a joint practice guideline on evaluating and managing chest pain that was endorsed by five other subspecialty groups. The next day, another group that had taken part in the document’s genesis explained why it wasn’t one of those five.

Although the American Society of Nuclear Cardiology (ASNC) was “actively engaged at every stage of the guideline-writing and review process,” the society “could not endorse the guideline,” the society announced in a statement released to clinicians and the media. The most prominent cited reason: It doesn’t adequately “support the principle of Patient First Imaging.”

The guideline was published in Circulation and the Journal of the American College of Cardiology, flagship journals of the American Heart Association and American College of Cardiology, respectively.

The document notes at least two clinicians represented ASNC as peer reviewers, and another was on the writing committee, but the organization does not appear in the list of societies endorsing the document.

“We believe that the document fails to provide unbiased guidance to health care professionals on the optimal evaluation of patients with chest pain,” contends an editorial ASNC board members have scheduled for the Jan. 10 issue of the Journal of Nuclear Medicine but is available now on an open-access preprint server.

“Despite the many important and helpful recommendations in the new guideline, there are several recommendations that we could not support,” it states.

“The ASNC board of directors reviewed the document twice during the endorsement process,” and the society “offered substantive comments after the first endorsement review, several of which were addressed,” Randall C. Thompson, MD, St. Luke’s Mid America Heart Institute and University of Missouri–Kansas City, said in an interview.

“However, some of the board’s concerns went unresolved. It was after the board’s second review, when the document had been declared finalized, that they voted not to endorse,” said Dr. Thompson, who is ASNC president.

“When we gather multiple organizations together to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of peer-reviewed, published literature and create clinical practice recommendations,” Guideline Writing Committee Chair Martha Gulati, MD, University of Arizona, Phoenix, told this news organization in a prepared statement.

“The ASNC had a representative on the writing committee who is a coauthor on the paper and actively participated throughout the writing process the past 4 years,” she said. “The final guideline reflects the latest evidence-based recommendations for the evaluation and diagnosis of chest pain, as agreed by the seven endorsing organizations.”

The document does not clearly note that an ASNC representative was on the writing committee. However, ASNC confirmed that Renee Bullock-Palmer, MD, Deborah Heart and Lung Center, Browns Mills, N.J., is a fellow of the ASNC and had represented the group as one of the coauthors. Two “official reviewers” of the document, however, are listed as ASNC representatives.
 

Points of contention

“The decision about which test to order can be a nuanced one, and cardiac imaging tests tend to be complementary,” elaborates the editorial on the issue of patient-centered management.

Careful patient selection for different tests is important, “and physician and technical local expertise, availability, quality of equipment, and patient preference are extremely important factors to consider. There is not enough emphasis on this important point,” contend the authors. “This is an important limitation of the guideline.”

Other issues of concern include “lack of balance in the document’s presentation of the science on FFR-CT [fractional flow reserve assessment with computed tomography] and its inappropriately prominent endorsement,” the editorial states.

The U.S. Food and Drug Administration–recognized “limitations and contraindications” to FFR-CT tend to be glossed over in the document, Dr. Thompson said. And most ASNC board members were “concerned with the prominent location of the recommendations for FFR-CT in various tables – especially since there was minimal-to-no discussion of the fact that it is currently provided by only one company, that it is not widely available nor covered routinely by health insurance carriers, and [that] the accuracy in the most relevant population is disputed.”

In other concerns, the document “inadequately discusses the benefit” of combining coronary artery calcium (CAC) scores with functional testing, which ASNC said it supports. For example, adding CAC scores to myocardial perfusion imaging improves its diagnostic accuracy and prognostic power.
 

Functional vs. anatomic testing?

Moreover, “it is no longer appropriate to bundle all types of stress testing together. All stress imaging tests have their unique advantages and limitations.” Yet, “the concept of the dichotomy of functional testing versus anatomic testing is a common theme in the guideline in many important patient groups,” the editorial states. That could overemphasize CT angiography and thus “blur distinction between different types of functional tests.”

Such concerns about “imbalance” in the portrayals of the two kinds of tests were “amplified by the problem of health insurance companies and radiologic benefits managers inappropriately substituting a test that was ordered by a physician with a different test,” Dr. Thompson elaborated. “There is the impression that some of them ‘cherry-pick’ certain guidelines and that this practice is harmful to patients.”

The ASNC currently does not plan its own corresponding guideline, he said. But the editorial says that “over the coming weeks and months ASNC will offer a series of webinars and other programs that address specific patient populations and dilemmas.” Also, “we will enhance our focus on programs to address quality and efficiency to support a patient-first approach to imaging.”

The five subspecialty groups that have endorsed the document are the American Society of Echocardiography, American College of Chest Physicians, Society for Academic Emergency Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance.

Dr. Thompson has reported no relevant financial relationships. Statements of disclosure for the other editorial writers are listed in the publication.

A version of this article first appeared on Medscape.com.

It was Oct. 28 when the two big North American cardiology societies issued a joint practice guideline on evaluating and managing chest pain that was endorsed by five other subspecialty groups. The next day, another group that had taken part in the document’s genesis explained why it wasn’t one of those five.

Although the American Society of Nuclear Cardiology (ASNC) was “actively engaged at every stage of the guideline-writing and review process,” the society “could not endorse the guideline,” the society announced in a statement released to clinicians and the media. The most prominent cited reason: It doesn’t adequately “support the principle of Patient First Imaging.”

The guideline was published in Circulation and the Journal of the American College of Cardiology, flagship journals of the American Heart Association and American College of Cardiology, respectively.

The document notes at least two clinicians represented ASNC as peer reviewers, and another was on the writing committee, but the organization does not appear in the list of societies endorsing the document.

“We believe that the document fails to provide unbiased guidance to health care professionals on the optimal evaluation of patients with chest pain,” contends an editorial ASNC board members have scheduled for the Jan. 10 issue of the Journal of Nuclear Medicine but is available now on an open-access preprint server.

“Despite the many important and helpful recommendations in the new guideline, there are several recommendations that we could not support,” it states.

“The ASNC board of directors reviewed the document twice during the endorsement process,” and the society “offered substantive comments after the first endorsement review, several of which were addressed,” Randall C. Thompson, MD, St. Luke’s Mid America Heart Institute and University of Missouri–Kansas City, said in an interview.

“However, some of the board’s concerns went unresolved. It was after the board’s second review, when the document had been declared finalized, that they voted not to endorse,” said Dr. Thompson, who is ASNC president.

“When we gather multiple organizations together to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of peer-reviewed, published literature and create clinical practice recommendations,” Guideline Writing Committee Chair Martha Gulati, MD, University of Arizona, Phoenix, told this news organization in a prepared statement.

“The ASNC had a representative on the writing committee who is a coauthor on the paper and actively participated throughout the writing process the past 4 years,” she said. “The final guideline reflects the latest evidence-based recommendations for the evaluation and diagnosis of chest pain, as agreed by the seven endorsing organizations.”

The document does not clearly note that an ASNC representative was on the writing committee. However, ASNC confirmed that Renee Bullock-Palmer, MD, Deborah Heart and Lung Center, Browns Mills, N.J., is a fellow of the ASNC and had represented the group as one of the coauthors. Two “official reviewers” of the document, however, are listed as ASNC representatives.
 

Points of contention

“The decision about which test to order can be a nuanced one, and cardiac imaging tests tend to be complementary,” elaborates the editorial on the issue of patient-centered management.

Careful patient selection for different tests is important, “and physician and technical local expertise, availability, quality of equipment, and patient preference are extremely important factors to consider. There is not enough emphasis on this important point,” contend the authors. “This is an important limitation of the guideline.”

Other issues of concern include “lack of balance in the document’s presentation of the science on FFR-CT [fractional flow reserve assessment with computed tomography] and its inappropriately prominent endorsement,” the editorial states.

The U.S. Food and Drug Administration–recognized “limitations and contraindications” to FFR-CT tend to be glossed over in the document, Dr. Thompson said. And most ASNC board members were “concerned with the prominent location of the recommendations for FFR-CT in various tables – especially since there was minimal-to-no discussion of the fact that it is currently provided by only one company, that it is not widely available nor covered routinely by health insurance carriers, and [that] the accuracy in the most relevant population is disputed.”

In other concerns, the document “inadequately discusses the benefit” of combining coronary artery calcium (CAC) scores with functional testing, which ASNC said it supports. For example, adding CAC scores to myocardial perfusion imaging improves its diagnostic accuracy and prognostic power.
 

Functional vs. anatomic testing?

Moreover, “it is no longer appropriate to bundle all types of stress testing together. All stress imaging tests have their unique advantages and limitations.” Yet, “the concept of the dichotomy of functional testing versus anatomic testing is a common theme in the guideline in many important patient groups,” the editorial states. That could overemphasize CT angiography and thus “blur distinction between different types of functional tests.”

Such concerns about “imbalance” in the portrayals of the two kinds of tests were “amplified by the problem of health insurance companies and radiologic benefits managers inappropriately substituting a test that was ordered by a physician with a different test,” Dr. Thompson elaborated. “There is the impression that some of them ‘cherry-pick’ certain guidelines and that this practice is harmful to patients.”

The ASNC currently does not plan its own corresponding guideline, he said. But the editorial says that “over the coming weeks and months ASNC will offer a series of webinars and other programs that address specific patient populations and dilemmas.” Also, “we will enhance our focus on programs to address quality and efficiency to support a patient-first approach to imaging.”

The five subspecialty groups that have endorsed the document are the American Society of Echocardiography, American College of Chest Physicians, Society for Academic Emergency Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance.

Dr. Thompson has reported no relevant financial relationships. Statements of disclosure for the other editorial writers are listed in the publication.

A version of this article first appeared on Medscape.com.

In patients with breast cancer, an impaired white-matter microstructure, identified by neuroimaging before chemotherapy, may be a risk factor for cognitive decline after chemotherapy.

“Cognitive decline is frequently observed after chemotherapy,” according to Michiel B. de Ruiter, PhD, a research scientist with the Netherlands Cancer Institute in Amsterdam. He specializes in cognitive neuroscience and was the lead author of a study published online Sept. 30, 2021, in the Journal of Clinical Oncology. Dr. de Ruiter and colleagues found that fractional anisotropy may demonstrate a low brain white-matter reserve which could be a risk factor for cognitive decline after chemotherapy for breast cancer treatment.

Cognitive decline after chemotherapy has been reported in 20%-40% of patients with cancer affecting quality of life and daily living skills. Studies have suggested that genetic makeup, advanced age, fatigue, and premorbid intelligence quotient are risk factors for chemotherapy-associated cognitive decline. Changes in the microstructure of brain white matter, known as brain reserve, have been reported after exposure to chemotherapy, but its link to cognitive decline is understudied. Several studies outside of oncology have used MRI to derive fractional anisotropy as a measure for brain reserve.

In the new JCO study, researchers examined fractional anisotropy, as measured by MRI, before chemotherapy. The analysis included 49 patients who underwent neuropsychological tests before treatment with anthracycline-based chemotherapy, then again at 6 months and 2 years after chemotherapy.

The results were compared with those of patients with breast cancer who did not receive systemic therapy and then with a control group consisting of patients without cancer.

A low fractional anisotropy score suggested cognitive decline more than 3 years after receiving chemotherapy treatment. The finding was independent of age, premorbid intelligence quotient, baseline fatigue and baseline cognitive complaints. And, having low premorbid intelligence quotient was an independent risk factor for chemotherapy-associated cognitive decline, which the authors said is in line with previous findings.

Fractional anisotropy did not predict cognitive decline in patients who did not receive systemic therapy, as well as patients in the control group.

The findings could possibly lead to the development a pretreatment assessment to screen for patients who may at risk for cognitive decline, the authors wrote. “Clinically validated assessments of white-matter reserve as assessed with an MRI scan may be part of a pretreatment screening. This could also aid in early identification of cognitive decline after chemotherapy, allowing targeted and early interventions to improve cognitive problems,” such as psychoeducation and cognitive rehabilitation.

No potential conflicts of interest were reported.

In patients with breast cancer, an impaired white-matter microstructure, identified by neuroimaging before chemotherapy, may be a risk factor for cognitive decline after chemotherapy.

“Cognitive decline is frequently observed after chemotherapy,” according to Michiel B. de Ruiter, PhD, a research scientist with the Netherlands Cancer Institute in Amsterdam. He specializes in cognitive neuroscience and was the lead author of a study published online Sept. 30, 2021, in the Journal of Clinical Oncology. Dr. de Ruiter and colleagues found that fractional anisotropy may demonstrate a low brain white-matter reserve which could be a risk factor for cognitive decline after chemotherapy for breast cancer treatment.

Cognitive decline after chemotherapy has been reported in 20%-40% of patients with cancer affecting quality of life and daily living skills. Studies have suggested that genetic makeup, advanced age, fatigue, and premorbid intelligence quotient are risk factors for chemotherapy-associated cognitive decline. Changes in the microstructure of brain white matter, known as brain reserve, have been reported after exposure to chemotherapy, but its link to cognitive decline is understudied. Several studies outside of oncology have used MRI to derive fractional anisotropy as a measure for brain reserve.

In the new JCO study, researchers examined fractional anisotropy, as measured by MRI, before chemotherapy. The analysis included 49 patients who underwent neuropsychological tests before treatment with anthracycline-based chemotherapy, then again at 6 months and 2 years after chemotherapy.

The results were compared with those of patients with breast cancer who did not receive systemic therapy and then with a control group consisting of patients without cancer.

A low fractional anisotropy score suggested cognitive decline more than 3 years after receiving chemotherapy treatment. The finding was independent of age, premorbid intelligence quotient, baseline fatigue and baseline cognitive complaints. And, having low premorbid intelligence quotient was an independent risk factor for chemotherapy-associated cognitive decline, which the authors said is in line with previous findings.

Fractional anisotropy did not predict cognitive decline in patients who did not receive systemic therapy, as well as patients in the control group.

The findings could possibly lead to the development a pretreatment assessment to screen for patients who may at risk for cognitive decline, the authors wrote. “Clinically validated assessments of white-matter reserve as assessed with an MRI scan may be part of a pretreatment screening. This could also aid in early identification of cognitive decline after chemotherapy, allowing targeted and early interventions to improve cognitive problems,” such as psychoeducation and cognitive rehabilitation.

No potential conflicts of interest were reported.

In patients with breast cancer, an impaired white-matter microstructure, identified by neuroimaging before chemotherapy, may be a risk factor for cognitive decline after chemotherapy.

“Cognitive decline is frequently observed after chemotherapy,” according to Michiel B. de Ruiter, PhD, a research scientist with the Netherlands Cancer Institute in Amsterdam. He specializes in cognitive neuroscience and was the lead author of a study published online Sept. 30, 2021, in the Journal of Clinical Oncology. Dr. de Ruiter and colleagues found that fractional anisotropy may demonstrate a low brain white-matter reserve which could be a risk factor for cognitive decline after chemotherapy for breast cancer treatment.

Cognitive decline after chemotherapy has been reported in 20%-40% of patients with cancer affecting quality of life and daily living skills. Studies have suggested that genetic makeup, advanced age, fatigue, and premorbid intelligence quotient are risk factors for chemotherapy-associated cognitive decline. Changes in the microstructure of brain white matter, known as brain reserve, have been reported after exposure to chemotherapy, but its link to cognitive decline is understudied. Several studies outside of oncology have used MRI to derive fractional anisotropy as a measure for brain reserve.

In the new JCO study, researchers examined fractional anisotropy, as measured by MRI, before chemotherapy. The analysis included 49 patients who underwent neuropsychological tests before treatment with anthracycline-based chemotherapy, then again at 6 months and 2 years after chemotherapy.

The results were compared with those of patients with breast cancer who did not receive systemic therapy and then with a control group consisting of patients without cancer.

A low fractional anisotropy score suggested cognitive decline more than 3 years after receiving chemotherapy treatment. The finding was independent of age, premorbid intelligence quotient, baseline fatigue and baseline cognitive complaints. And, having low premorbid intelligence quotient was an independent risk factor for chemotherapy-associated cognitive decline, which the authors said is in line with previous findings.

Fractional anisotropy did not predict cognitive decline in patients who did not receive systemic therapy, as well as patients in the control group.

The findings could possibly lead to the development a pretreatment assessment to screen for patients who may at risk for cognitive decline, the authors wrote. “Clinically validated assessments of white-matter reserve as assessed with an MRI scan may be part of a pretreatment screening. This could also aid in early identification of cognitive decline after chemotherapy, allowing targeted and early interventions to improve cognitive problems,” such as psychoeducation and cognitive rehabilitation.

No potential conflicts of interest were reported.

New risk equations can help determine the need for a first coronary artery calcium (CAC) scan in young adults to identify those most at risk for premature atherosclerosis, researchers say.

“To our knowledge this is the first time to derive a clinical risk equation for the initial conversion from CAC 0, which can be used actually to guide the timing of CAC testing in young adults,” Omar Dzaye, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, said in an interview.

CAC is an independent predictor of adverse atherosclerotic cardiovascular disease (ASCVD), but routine screening is not recommended in low-risk groups. U.S. guidelines say CAC testing may be considered (class IIa) for risk stratification in adults 40 to 75 years at intermediate risk (estimated 10-year ASCVD risk 7.5% to 20%) when the decision to start preventive therapies is unclear.

The new sex-specific risk equations were derived from 22,346 adults 30 to 50 years of age who underwent CAC testing between 1991 and 2010 for ASCVD risk prediction at four high-volume centers in the CAC Consortium. The average age was 43.5 years, 25% were women, and 12.3% were non-White.

The participants were free of clinical ASCVD or CV symptoms at the time of scanning but had underlying traditional ASCVD risk factors (dyslipidemia in 49.6%, hypertension in 20.0%, active smokers 11.0%, and diabetes in 4.0%), an intermediate 10-year ASCVD risk (2.6%), and/or a significant family history of CHD (49.3%).

As reported in the Journal of the American College of Cardiology, 92.7% of participants had a low 10-year ASCVD risk below 5%, but 34.4% had CAC scores above 0 (median, 20 Agatston units).

Assuming a 25% testing yield (number needed to scan equals four to detect one CAC score above 0), the optimal age for a first scan in young men without risk factors was 42.3 years, and for women it was 57.6 years.

Young adults with one or more risk factors, however, would convert to CAC above 0 at least 3.3 years earlier on average. Diabetes had the strongest influence on the probability of conversion, with men and women predicted to develop incident CAC a respective 5.5 years and 7.3 years earlier on average.

The findings build on previous observations by the team showing that diabetes confers a 40% reduction in the so-called “warranty period” of a CAC score of 0, Dr. Dzaye noted. The National Lipid Association 2020 statement on CAC scoring also suggests it’s reasonable to obtain a CAC scan in people with diabetes aged 30 to 39 years.

“The predicted utility of CAC for ASCVD outcomes is similar in type 1 and type 2 diabetes; however, individuals with type 1 diabetes may actually develop CAC as young as 17 years of age,” he said. “Therefore, definitely, CAC studies in this population are required.”

In contrast, hypertension, dyslipidemia, active smoking, and a family history of CHD were individually associated with the development of CAC 3.3 to 4.3 years earlier. In general, the time to premature CAC was longer for women than for men with a given risk-factor profile.

The predicted age for a first CAC was 37.5 years for men and 48.9 years for women with an intermediate risk-factor profile (for example, smoking plus hypertension) and 33.8 years and 44.7 years, respectively, for those with a high-risk profile (for example, diabetes plus dyslipidemia).

Asked whether the risk equations can be used to guide CAC scanning in clinical practice, Dr. Dzaye said, “we very much believe that this can be used because for the process we published the internal validation, and we also did an external validation that is not published at the moment in [the] MESA [trial].”

He pointed out that study participants did not have a second CAC scan for true modeling of longitudinal CAC and do not represent the general population but, rather, a general cardiology referral population enriched with ASCVD risk factors. Future studies are needed that incorporate a more diverse population, multiple CAC scans, and genetic risk factors.

“This is helpful from a descriptive, epidemiologic point of view and helps us understand the approximate prevalence of coronary calcium greater than 0 in younger men and women, but I’m not convinced that it will or should change clinical practice,” cardiologist Philip Greenland, MD, a professor of preventive medicine and professor of medicine at Northwestern University in Chicago, said in an interview.

Dr. Greenland, who coauthored a review on CAC testing earlier this month, said CAC is the strongest tool we have to improve risk prediction beyond standard risk scores but does involve radiation exposure and some added costs. CAC testing is especially useful as a tiebreaker in older intermediate-risk patients who may be on the fence about starting primary prevention medications but could fall short among “younger, low-risk patients where, as they show here, the proportion of people who have a positive test is well below half.”

“So that means you’re going to have a very large number of people who are CAC 0, which is what we would expect in relatively younger people, but I wouldn’t be happy to try to explain that to a patient: ‘We’re not seeing coronary atherosclerosis right now, but we still want to treat your risk factors.’ That’s kind of a dissonant message,” Dr. Greenland said.

An accompanying editorial suggests “the study has filled an important clinical gap, providing highly actionable data that could help guide clinical decision making for ASCVD prevention.”

Nevertheless, Tasneem Naqvi, MD, Mayo Clinic, Scottsdale, Arizona, and Tamar Polonsky, MD, University of Chicago, question the generalizability of the results and point out that CAC screening at the authors’ recommended ages “could still miss a substantial number of young women with incident MI.”

Exposure to ionizing radiation with CAC is lower than that used in screening mammography for breast cancer but, they agree, should be considered, particularly in young women.

“Alternatively, ultrasonography avoids radiation altogether and can detect plaque earlier than the development of CAC,” write Dr. Naqvi and Dr. Polonsky. Further, the 2019 European Society of Cardiology guidelines for CV risk give ultrasound assessment of carotid artery and femoral plaque a class IIa recommendation and CAC a class IIb recommendation.

Commenting for this news organization, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the class IIb recommendation “never really made any sense because the data with coronary calcium is so much stronger than it is with carotid ultrasound.”

“Sometimes smart scientists and researchers differ, but in my strong opinion, the European Society of Cardiology in 2019 did not give it the right classification, while the group I was part of, the American Heart Association/American College of Cardiology [2019 guideline], got it right and emphasized that this is the most cost-effective and useful way to improve risk assessment.”

Dr. Blumenthal, who was not part of the study, noted that U.S. guidelines say CAC measurement is not intended as a screening test for everyone but may be used selectively as a decision aid.

“This study adds to the information about how to use that type of testing. So, I personally think it will be a highly referenced article in the next set of guidelines that the American Heart Association, American College of Cardiology, and other organizations have.”

The study was supported in part by a research grant from the National Institutes of Health National Heart, Lung, and Blood Institute. Dr. Dzaye, Dr. Blumenthal, Dr. Naqvi, and Dr. Polonsky report having no relevant financial relationships.

A version of this article appeared on Medscape.com.

New risk equations can help determine the need for a first coronary artery calcium (CAC) scan in young adults to identify those most at risk for premature atherosclerosis, researchers say.

“To our knowledge this is the first time to derive a clinical risk equation for the initial conversion from CAC 0, which can be used actually to guide the timing of CAC testing in young adults,” Omar Dzaye, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, said in an interview.

CAC is an independent predictor of adverse atherosclerotic cardiovascular disease (ASCVD), but routine screening is not recommended in low-risk groups. U.S. guidelines say CAC testing may be considered (class IIa) for risk stratification in adults 40 to 75 years at intermediate risk (estimated 10-year ASCVD risk 7.5% to 20%) when the decision to start preventive therapies is unclear.

The new sex-specific risk equations were derived from 22,346 adults 30 to 50 years of age who underwent CAC testing between 1991 and 2010 for ASCVD risk prediction at four high-volume centers in the CAC Consortium. The average age was 43.5 years, 25% were women, and 12.3% were non-White.

The participants were free of clinical ASCVD or CV symptoms at the time of scanning but had underlying traditional ASCVD risk factors (dyslipidemia in 49.6%, hypertension in 20.0%, active smokers 11.0%, and diabetes in 4.0%), an intermediate 10-year ASCVD risk (2.6%), and/or a significant family history of CHD (49.3%).

As reported in the Journal of the American College of Cardiology, 92.7% of participants had a low 10-year ASCVD risk below 5%, but 34.4% had CAC scores above 0 (median, 20 Agatston units).

Assuming a 25% testing yield (number needed to scan equals four to detect one CAC score above 0), the optimal age for a first scan in young men without risk factors was 42.3 years, and for women it was 57.6 years.

Young adults with one or more risk factors, however, would convert to CAC above 0 at least 3.3 years earlier on average. Diabetes had the strongest influence on the probability of conversion, with men and women predicted to develop incident CAC a respective 5.5 years and 7.3 years earlier on average.

The findings build on previous observations by the team showing that diabetes confers a 40% reduction in the so-called “warranty period” of a CAC score of 0, Dr. Dzaye noted. The National Lipid Association 2020 statement on CAC scoring also suggests it’s reasonable to obtain a CAC scan in people with diabetes aged 30 to 39 years.

“The predicted utility of CAC for ASCVD outcomes is similar in type 1 and type 2 diabetes; however, individuals with type 1 diabetes may actually develop CAC as young as 17 years of age,” he said. “Therefore, definitely, CAC studies in this population are required.”

In contrast, hypertension, dyslipidemia, active smoking, and a family history of CHD were individually associated with the development of CAC 3.3 to 4.3 years earlier. In general, the time to premature CAC was longer for women than for men with a given risk-factor profile.

The predicted age for a first CAC was 37.5 years for men and 48.9 years for women with an intermediate risk-factor profile (for example, smoking plus hypertension) and 33.8 years and 44.7 years, respectively, for those with a high-risk profile (for example, diabetes plus dyslipidemia).

Asked whether the risk equations can be used to guide CAC scanning in clinical practice, Dr. Dzaye said, “we very much believe that this can be used because for the process we published the internal validation, and we also did an external validation that is not published at the moment in [the] MESA [trial].”

He pointed out that study participants did not have a second CAC scan for true modeling of longitudinal CAC and do not represent the general population but, rather, a general cardiology referral population enriched with ASCVD risk factors. Future studies are needed that incorporate a more diverse population, multiple CAC scans, and genetic risk factors.

“This is helpful from a descriptive, epidemiologic point of view and helps us understand the approximate prevalence of coronary calcium greater than 0 in younger men and women, but I’m not convinced that it will or should change clinical practice,” cardiologist Philip Greenland, MD, a professor of preventive medicine and professor of medicine at Northwestern University in Chicago, said in an interview.

Dr. Greenland, who coauthored a review on CAC testing earlier this month, said CAC is the strongest tool we have to improve risk prediction beyond standard risk scores but does involve radiation exposure and some added costs. CAC testing is especially useful as a tiebreaker in older intermediate-risk patients who may be on the fence about starting primary prevention medications but could fall short among “younger, low-risk patients where, as they show here, the proportion of people who have a positive test is well below half.”

“So that means you’re going to have a very large number of people who are CAC 0, which is what we would expect in relatively younger people, but I wouldn’t be happy to try to explain that to a patient: ‘We’re not seeing coronary atherosclerosis right now, but we still want to treat your risk factors.’ That’s kind of a dissonant message,” Dr. Greenland said.

An accompanying editorial suggests “the study has filled an important clinical gap, providing highly actionable data that could help guide clinical decision making for ASCVD prevention.”

Nevertheless, Tasneem Naqvi, MD, Mayo Clinic, Scottsdale, Arizona, and Tamar Polonsky, MD, University of Chicago, question the generalizability of the results and point out that CAC screening at the authors’ recommended ages “could still miss a substantial number of young women with incident MI.”

Exposure to ionizing radiation with CAC is lower than that used in screening mammography for breast cancer but, they agree, should be considered, particularly in young women.

“Alternatively, ultrasonography avoids radiation altogether and can detect plaque earlier than the development of CAC,” write Dr. Naqvi and Dr. Polonsky. Further, the 2019 European Society of Cardiology guidelines for CV risk give ultrasound assessment of carotid artery and femoral plaque a class IIa recommendation and CAC a class IIb recommendation.

Commenting for this news organization, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the class IIb recommendation “never really made any sense because the data with coronary calcium is so much stronger than it is with carotid ultrasound.”

“Sometimes smart scientists and researchers differ, but in my strong opinion, the European Society of Cardiology in 2019 did not give it the right classification, while the group I was part of, the American Heart Association/American College of Cardiology [2019 guideline], got it right and emphasized that this is the most cost-effective and useful way to improve risk assessment.”

Dr. Blumenthal, who was not part of the study, noted that U.S. guidelines say CAC measurement is not intended as a screening test for everyone but may be used selectively as a decision aid.

“This study adds to the information about how to use that type of testing. So, I personally think it will be a highly referenced article in the next set of guidelines that the American Heart Association, American College of Cardiology, and other organizations have.”

The study was supported in part by a research grant from the National Institutes of Health National Heart, Lung, and Blood Institute. Dr. Dzaye, Dr. Blumenthal, Dr. Naqvi, and Dr. Polonsky report having no relevant financial relationships.

A version of this article appeared on Medscape.com.

New risk equations can help determine the need for a first coronary artery calcium (CAC) scan in young adults to identify those most at risk for premature atherosclerosis, researchers say.

“To our knowledge this is the first time to derive a clinical risk equation for the initial conversion from CAC 0, which can be used actually to guide the timing of CAC testing in young adults,” Omar Dzaye, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, said in an interview.

CAC is an independent predictor of adverse atherosclerotic cardiovascular disease (ASCVD), but routine screening is not recommended in low-risk groups. U.S. guidelines say CAC testing may be considered (class IIa) for risk stratification in adults 40 to 75 years at intermediate risk (estimated 10-year ASCVD risk 7.5% to 20%) when the decision to start preventive therapies is unclear.

The new sex-specific risk equations were derived from 22,346 adults 30 to 50 years of age who underwent CAC testing between 1991 and 2010 for ASCVD risk prediction at four high-volume centers in the CAC Consortium. The average age was 43.5 years, 25% were women, and 12.3% were non-White.

The participants were free of clinical ASCVD or CV symptoms at the time of scanning but had underlying traditional ASCVD risk factors (dyslipidemia in 49.6%, hypertension in 20.0%, active smokers 11.0%, and diabetes in 4.0%), an intermediate 10-year ASCVD risk (2.6%), and/or a significant family history of CHD (49.3%).

As reported in the Journal of the American College of Cardiology, 92.7% of participants had a low 10-year ASCVD risk below 5%, but 34.4% had CAC scores above 0 (median, 20 Agatston units).

Assuming a 25% testing yield (number needed to scan equals four to detect one CAC score above 0), the optimal age for a first scan in young men without risk factors was 42.3 years, and for women it was 57.6 years.

Young adults with one or more risk factors, however, would convert to CAC above 0 at least 3.3 years earlier on average. Diabetes had the strongest influence on the probability of conversion, with men and women predicted to develop incident CAC a respective 5.5 years and 7.3 years earlier on average.

The findings build on previous observations by the team showing that diabetes confers a 40% reduction in the so-called “warranty period” of a CAC score of 0, Dr. Dzaye noted. The National Lipid Association 2020 statement on CAC scoring also suggests it’s reasonable to obtain a CAC scan in people with diabetes aged 30 to 39 years.

“The predicted utility of CAC for ASCVD outcomes is similar in type 1 and type 2 diabetes; however, individuals with type 1 diabetes may actually develop CAC as young as 17 years of age,” he said. “Therefore, definitely, CAC studies in this population are required.”

In contrast, hypertension, dyslipidemia, active smoking, and a family history of CHD were individually associated with the development of CAC 3.3 to 4.3 years earlier. In general, the time to premature CAC was longer for women than for men with a given risk-factor profile.

The predicted age for a first CAC was 37.5 years for men and 48.9 years for women with an intermediate risk-factor profile (for example, smoking plus hypertension) and 33.8 years and 44.7 years, respectively, for those with a high-risk profile (for example, diabetes plus dyslipidemia).

Asked whether the risk equations can be used to guide CAC scanning in clinical practice, Dr. Dzaye said, “we very much believe that this can be used because for the process we published the internal validation, and we also did an external validation that is not published at the moment in [the] MESA [trial].”

He pointed out that study participants did not have a second CAC scan for true modeling of longitudinal CAC and do not represent the general population but, rather, a general cardiology referral population enriched with ASCVD risk factors. Future studies are needed that incorporate a more diverse population, multiple CAC scans, and genetic risk factors.

“This is helpful from a descriptive, epidemiologic point of view and helps us understand the approximate prevalence of coronary calcium greater than 0 in younger men and women, but I’m not convinced that it will or should change clinical practice,” cardiologist Philip Greenland, MD, a professor of preventive medicine and professor of medicine at Northwestern University in Chicago, said in an interview.

Dr. Greenland, who coauthored a review on CAC testing earlier this month, said CAC is the strongest tool we have to improve risk prediction beyond standard risk scores but does involve radiation exposure and some added costs. CAC testing is especially useful as a tiebreaker in older intermediate-risk patients who may be on the fence about starting primary prevention medications but could fall short among “younger, low-risk patients where, as they show here, the proportion of people who have a positive test is well below half.”

“So that means you’re going to have a very large number of people who are CAC 0, which is what we would expect in relatively younger people, but I wouldn’t be happy to try to explain that to a patient: ‘We’re not seeing coronary atherosclerosis right now, but we still want to treat your risk factors.’ That’s kind of a dissonant message,” Dr. Greenland said.

An accompanying editorial suggests “the study has filled an important clinical gap, providing highly actionable data that could help guide clinical decision making for ASCVD prevention.”

Nevertheless, Tasneem Naqvi, MD, Mayo Clinic, Scottsdale, Arizona, and Tamar Polonsky, MD, University of Chicago, question the generalizability of the results and point out that CAC screening at the authors’ recommended ages “could still miss a substantial number of young women with incident MI.”

Exposure to ionizing radiation with CAC is lower than that used in screening mammography for breast cancer but, they agree, should be considered, particularly in young women.

“Alternatively, ultrasonography avoids radiation altogether and can detect plaque earlier than the development of CAC,” write Dr. Naqvi and Dr. Polonsky. Further, the 2019 European Society of Cardiology guidelines for CV risk give ultrasound assessment of carotid artery and femoral plaque a class IIa recommendation and CAC a class IIb recommendation.

Commenting for this news organization, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the class IIb recommendation “never really made any sense because the data with coronary calcium is so much stronger than it is with carotid ultrasound.”

“Sometimes smart scientists and researchers differ, but in my strong opinion, the European Society of Cardiology in 2019 did not give it the right classification, while the group I was part of, the American Heart Association/American College of Cardiology [2019 guideline], got it right and emphasized that this is the most cost-effective and useful way to improve risk assessment.”

Dr. Blumenthal, who was not part of the study, noted that U.S. guidelines say CAC measurement is not intended as a screening test for everyone but may be used selectively as a decision aid.

“This study adds to the information about how to use that type of testing. So, I personally think it will be a highly referenced article in the next set of guidelines that the American Heart Association, American College of Cardiology, and other organizations have.”

The study was supported in part by a research grant from the National Institutes of Health National Heart, Lung, and Blood Institute. Dr. Dzaye, Dr. Blumenthal, Dr. Naqvi, and Dr. Polonsky report having no relevant financial relationships.

A version of this article appeared on Medscape.com.