Cardiology News

In what may be the first randomized trial to compare coronary intervention access using the distal or proximal radial arteries, researchers have found no significant differences between the two in hand function a year after the procedure.

The distal radial artery (DRA) access point is just below the thumb on the inside of the wrist. The proximal radial artery (PRA) entry is in the inside lower forearm above the wrist.

“There has been growing interest in the use of distal radial access given its ease of hemostasis, lower incidence of radial artery occlusions, as well as the more ergonomic favorable setup for a left radial access, which is typically utilized in patients with prior CABG who undergo a cardiac catheterization when used as alternative to femoral artery access,” Karim Al-Azizi, MD, of Texas A&M University, an interventional cardiologist and associate program director of the cardiology fellowship at  Baylor Scott & White Health, in Plano, Tex., said in an interview.

Baylor Scott & White

Dr Al-Azizi presented the late-breaking 1-year results of the DIPRA–for Distal vs. Proximal Radial Artery–study at the Society for Cardiovascular Angiography & Interventions annual scientific sessions. The 30-day results of the DIPRA trial were presented in 2022 at this meeting.

Dr. Al-Azizi said DIPRA is the first randomized, controlled trial comparing hand function outcomes with the two approaches. “I think the biggest question for most investigators and most practitioners is that, is this safe on the hand? Are we doing the right thing by going into the radial artery in the anatomical snuff box in proximity to the radial nerve and would that affect motor function?” he said. “And it does not seem like it from a head-to-head comparison of proximal versus distal access.”

The DIPRA study randomized 300 patients 1:1 to cardiac catheterization through either the distal or proximal access. Of those, 216 completed 1-year follow-up, 112 randomized to DRA and 104 to PRA.

The study used three metrics to evaluate hand function: hand-grip strength; pinch test, which measured the strength of a pinch between the thumb and index finger; and QuickDASH, an abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire, in which participants self-evaluate their hand function. Study protocol mandated that operators use ultrasound guidance for DRA access.

The 1-year results of all three measures showed no significant difference in change of hand function from baseline between the two groups. The composite average score change was –0.07 (–0.41, 0.44) for the DRA patients and –0.03. (–0.36, 0.44) for the PRA group (P = .59).

One-year change for the specific hand function measures for DRA and PRA, respectively, were: hand grip, 0.7 (–3, 4.5) vs. 1.3 (–2, 4.3) kg (P = .57); pinch grip, –0.1 (–1.1, 1) vs. –0.3 (–1, 0.7) kg (P = .66); and none for change in the QuickDASH score (–6.6, 2.3 vs. –4.6, 2.9) points (P = .58).

Outcomes at intervention were also similar. Bleeding incidence was 0% and 1.4% (P = .25) in the respective groups. Successful RA access was achieved in 96.7% and 98% (P = .72).

Baseline characteristics were balanced between the two groups: 75% were male; mean age was 66.6 ± 9.6 years; 32% had diabetes; 77% had hypertension; and 19% had a previous percutaneous coronary intervention.

One key strength of the DIPRA study Dr. Al-Azizi noted is that it included some investigators who were at the early stage of the learning curve with the procedure. A limitation is that it didn’t evaluate hand numbness or tingling, but hand sensory testing is “very subjective,” he said. “To avoid confusion, we decided to go with the more repeatable questionnaire rather than a sensation or sensory test,” he added.

The next step for his research team is to conduct a meta-analysis of studies that have evaluated DRA and PRA, Dr. Al-Azizi said.
 

‘Slow to the party’

U.S. interventional cardiologists have been “slow to the party” in adopting radial artery access for PCI, said David A. Cox, MD, of Sanger Heart and Vascular Institute in Charlotte, N.C., and SCAI communications committee chair. Even now uptake is low, compared with the rest of the world, he said.

“I can tell you what patients care about: Did you have to stick my groin?” he said at a SCAI press conference. “What they just want to know is that there are no issues with hand function.”

Some patients who need fine motor hand function would still opt for femoral access, he said.

“Are we looking at the right metric?” he asked Dr. Al-Azizi. “It took a long time to get American doctors to stick the radial, so why would I want to learn distal radial artery if I’m really pretty good at proximal and if it’s not inferior?”

Dr. Al-Azizi noted that previous studies showed a trend toward a lower incidence of radial artery occlusion (RAO) with DRA access. It also better preserves the renal arteries for dialysis and CABG, he said.

“The metric that would move the needle,” Dr. Cox noted, “is if you had radial artery occlusion rates vs. snuff box occlusion rates, and we don’t have that rate.”

Dr. Al-Azizi has no relevant financial disclosures. Dr. Cox disclosed financial relationships with Medtronic.

In what may be the first randomized trial to compare coronary intervention access using the distal or proximal radial arteries, researchers have found no significant differences between the two in hand function a year after the procedure.

The distal radial artery (DRA) access point is just below the thumb on the inside of the wrist. The proximal radial artery (PRA) entry is in the inside lower forearm above the wrist.

“There has been growing interest in the use of distal radial access given its ease of hemostasis, lower incidence of radial artery occlusions, as well as the more ergonomic favorable setup for a left radial access, which is typically utilized in patients with prior CABG who undergo a cardiac catheterization when used as alternative to femoral artery access,” Karim Al-Azizi, MD, of Texas A&M University, an interventional cardiologist and associate program director of the cardiology fellowship at  Baylor Scott & White Health, in Plano, Tex., said in an interview.

Baylor Scott & White

Dr Al-Azizi presented the late-breaking 1-year results of the DIPRA–for Distal vs. Proximal Radial Artery–study at the Society for Cardiovascular Angiography & Interventions annual scientific sessions. The 30-day results of the DIPRA trial were presented in 2022 at this meeting.

Dr. Al-Azizi said DIPRA is the first randomized, controlled trial comparing hand function outcomes with the two approaches. “I think the biggest question for most investigators and most practitioners is that, is this safe on the hand? Are we doing the right thing by going into the radial artery in the anatomical snuff box in proximity to the radial nerve and would that affect motor function?” he said. “And it does not seem like it from a head-to-head comparison of proximal versus distal access.”

The DIPRA study randomized 300 patients 1:1 to cardiac catheterization through either the distal or proximal access. Of those, 216 completed 1-year follow-up, 112 randomized to DRA and 104 to PRA.

The study used three metrics to evaluate hand function: hand-grip strength; pinch test, which measured the strength of a pinch between the thumb and index finger; and QuickDASH, an abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire, in which participants self-evaluate their hand function. Study protocol mandated that operators use ultrasound guidance for DRA access.

The 1-year results of all three measures showed no significant difference in change of hand function from baseline between the two groups. The composite average score change was –0.07 (–0.41, 0.44) for the DRA patients and –0.03. (–0.36, 0.44) for the PRA group (P = .59).

One-year change for the specific hand function measures for DRA and PRA, respectively, were: hand grip, 0.7 (–3, 4.5) vs. 1.3 (–2, 4.3) kg (P = .57); pinch grip, –0.1 (–1.1, 1) vs. –0.3 (–1, 0.7) kg (P = .66); and none for change in the QuickDASH score (–6.6, 2.3 vs. –4.6, 2.9) points (P = .58).

Outcomes at intervention were also similar. Bleeding incidence was 0% and 1.4% (P = .25) in the respective groups. Successful RA access was achieved in 96.7% and 98% (P = .72).

Baseline characteristics were balanced between the two groups: 75% were male; mean age was 66.6 ± 9.6 years; 32% had diabetes; 77% had hypertension; and 19% had a previous percutaneous coronary intervention.

One key strength of the DIPRA study Dr. Al-Azizi noted is that it included some investigators who were at the early stage of the learning curve with the procedure. A limitation is that it didn’t evaluate hand numbness or tingling, but hand sensory testing is “very subjective,” he said. “To avoid confusion, we decided to go with the more repeatable questionnaire rather than a sensation or sensory test,” he added.

The next step for his research team is to conduct a meta-analysis of studies that have evaluated DRA and PRA, Dr. Al-Azizi said.
 

‘Slow to the party’

U.S. interventional cardiologists have been “slow to the party” in adopting radial artery access for PCI, said David A. Cox, MD, of Sanger Heart and Vascular Institute in Charlotte, N.C., and SCAI communications committee chair. Even now uptake is low, compared with the rest of the world, he said.

“I can tell you what patients care about: Did you have to stick my groin?” he said at a SCAI press conference. “What they just want to know is that there are no issues with hand function.”

Some patients who need fine motor hand function would still opt for femoral access, he said.

“Are we looking at the right metric?” he asked Dr. Al-Azizi. “It took a long time to get American doctors to stick the radial, so why would I want to learn distal radial artery if I’m really pretty good at proximal and if it’s not inferior?”

Dr. Al-Azizi noted that previous studies showed a trend toward a lower incidence of radial artery occlusion (RAO) with DRA access. It also better preserves the renal arteries for dialysis and CABG, he said.

“The metric that would move the needle,” Dr. Cox noted, “is if you had radial artery occlusion rates vs. snuff box occlusion rates, and we don’t have that rate.”

Dr. Al-Azizi has no relevant financial disclosures. Dr. Cox disclosed financial relationships with Medtronic.

In what may be the first randomized trial to compare coronary intervention access using the distal or proximal radial arteries, researchers have found no significant differences between the two in hand function a year after the procedure.

The distal radial artery (DRA) access point is just below the thumb on the inside of the wrist. The proximal radial artery (PRA) entry is in the inside lower forearm above the wrist.

“There has been growing interest in the use of distal radial access given its ease of hemostasis, lower incidence of radial artery occlusions, as well as the more ergonomic favorable setup for a left radial access, which is typically utilized in patients with prior CABG who undergo a cardiac catheterization when used as alternative to femoral artery access,” Karim Al-Azizi, MD, of Texas A&M University, an interventional cardiologist and associate program director of the cardiology fellowship at  Baylor Scott & White Health, in Plano, Tex., said in an interview.

Baylor Scott & White

Dr Al-Azizi presented the late-breaking 1-year results of the DIPRA–for Distal vs. Proximal Radial Artery–study at the Society for Cardiovascular Angiography & Interventions annual scientific sessions. The 30-day results of the DIPRA trial were presented in 2022 at this meeting.

Dr. Al-Azizi said DIPRA is the first randomized, controlled trial comparing hand function outcomes with the two approaches. “I think the biggest question for most investigators and most practitioners is that, is this safe on the hand? Are we doing the right thing by going into the radial artery in the anatomical snuff box in proximity to the radial nerve and would that affect motor function?” he said. “And it does not seem like it from a head-to-head comparison of proximal versus distal access.”

The DIPRA study randomized 300 patients 1:1 to cardiac catheterization through either the distal or proximal access. Of those, 216 completed 1-year follow-up, 112 randomized to DRA and 104 to PRA.

The study used three metrics to evaluate hand function: hand-grip strength; pinch test, which measured the strength of a pinch between the thumb and index finger; and QuickDASH, an abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire, in which participants self-evaluate their hand function. Study protocol mandated that operators use ultrasound guidance for DRA access.

The 1-year results of all three measures showed no significant difference in change of hand function from baseline between the two groups. The composite average score change was –0.07 (–0.41, 0.44) for the DRA patients and –0.03. (–0.36, 0.44) for the PRA group (P = .59).

One-year change for the specific hand function measures for DRA and PRA, respectively, were: hand grip, 0.7 (–3, 4.5) vs. 1.3 (–2, 4.3) kg (P = .57); pinch grip, –0.1 (–1.1, 1) vs. –0.3 (–1, 0.7) kg (P = .66); and none for change in the QuickDASH score (–6.6, 2.3 vs. –4.6, 2.9) points (P = .58).

Outcomes at intervention were also similar. Bleeding incidence was 0% and 1.4% (P = .25) in the respective groups. Successful RA access was achieved in 96.7% and 98% (P = .72).

Baseline characteristics were balanced between the two groups: 75% were male; mean age was 66.6 ± 9.6 years; 32% had diabetes; 77% had hypertension; and 19% had a previous percutaneous coronary intervention.

One key strength of the DIPRA study Dr. Al-Azizi noted is that it included some investigators who were at the early stage of the learning curve with the procedure. A limitation is that it didn’t evaluate hand numbness or tingling, but hand sensory testing is “very subjective,” he said. “To avoid confusion, we decided to go with the more repeatable questionnaire rather than a sensation or sensory test,” he added.

The next step for his research team is to conduct a meta-analysis of studies that have evaluated DRA and PRA, Dr. Al-Azizi said.
 

‘Slow to the party’

U.S. interventional cardiologists have been “slow to the party” in adopting radial artery access for PCI, said David A. Cox, MD, of Sanger Heart and Vascular Institute in Charlotte, N.C., and SCAI communications committee chair. Even now uptake is low, compared with the rest of the world, he said.

“I can tell you what patients care about: Did you have to stick my groin?” he said at a SCAI press conference. “What they just want to know is that there are no issues with hand function.”

Some patients who need fine motor hand function would still opt for femoral access, he said.

“Are we looking at the right metric?” he asked Dr. Al-Azizi. “It took a long time to get American doctors to stick the radial, so why would I want to learn distal radial artery if I’m really pretty good at proximal and if it’s not inferior?”

Dr. Al-Azizi noted that previous studies showed a trend toward a lower incidence of radial artery occlusion (RAO) with DRA access. It also better preserves the renal arteries for dialysis and CABG, he said.

“The metric that would move the needle,” Dr. Cox noted, “is if you had radial artery occlusion rates vs. snuff box occlusion rates, and we don’t have that rate.”

Dr. Al-Azizi has no relevant financial disclosures. Dr. Cox disclosed financial relationships with Medtronic.

Use of a machine-learning model that incorporates information from a single troponin test as well as other clinical data was superior to current practice as an aid to the diagnosis of myocardial infarction in the emergency department in a new study.

“Our results suggest that by using this machine-learning model, compared to the currently recommended approach, we could double the proportion of patients who are identified correctly as having a low probability of an MI on arrival to enable immediate discharge and free up space in the emergency department,” senior author Nicholas L. Mills, MD, University of Edinburgh, Scotland, said in an interview.

“And, perhaps even more importantly, use of this model could also increase the proportion of patients who are correctly identified as at a high probability of having an MI,” he added.

The study was published online in Nature Medicine.

The authors explained that at present, the likelihood of an MI diagnosis for patients presenting to the emergency department with chest pain is based on a fixed troponin threshold in serial tests at specific time points, but there are several problems with this approach.

First, a fixed troponin threshold is generally used for all patients, which does not account for age, sex, or comorbidities that are known to influence cardiac troponin concentrations. Second, the need to perform tests at specific time points for serial testing can be challenging in busy emergency departments.

And third, patients are categorized as being at low, intermediate, or high risk of MI on the basis of troponin thresholds alone, and the test does not take into account other important factors, such as the time of symptom onset or findings on the electrocardiogram.

“Our current practice of using the same threshold to rule in and rule out an MI for everyone, regardless of whether they are an 18-year-old female without a history of heart disease or an 85-year-old male with known heart failure, doesn’t perform well, and there’s a significant risk of misdiagnosis. There is also a high likelihood for inequalities in care, particularly between men and women,” Dr. Mills said.

The current study evaluated whether use of a machine learning model known as CoDE-ACS to guide decision-making could overcome some of these challenges.

The machine learning model assesses the whole spectrum of troponin levels as a continuous variable (rather than use of a single threshold) and turns this measurement into a probability that an individual patient is having an MI after accounting for other factors, including age, sex, comorbidities, and time from symptom onset.

For the current study, the CoDE-ACS model was trained in 10,000 patients with suspected acute coronary syndrome (ACS) who presented to 10 hospitals in Scotland as part of the High-STEACS trial evaluating the implementation of a high-sensitivity cardiac troponin I assay. The results were then validated in another 10,000 patients from six countries around the world.

“Using this model, the patient can have a troponin test on arrival at the emergency department. The other information on age, sex, clinical history, and time since symptom onset is keyed in, and it gives a probability on a scale of 0–100 as to whether the patient is having an MI,” Dr. Mills noted.

“It also has the capacity to incorporate more information over time. So, if there is a second troponin measurement made, then the model automatically refines the probability score,” he added.

The current study showed that use of the CoDE-ACS model identified more patients at presentation as having a low probability of having an MI than fixed cardiac troponin thresholds (61% vs. 27%) with a similar negative predictive value.

It also identified fewer patients as having a high probability of having an MI (10% vs. 16%) with a greater positive predictive value.

Among patients who were identified as having a low probability of MI, the rate of cardiac death was lower than the rate among those with intermediate or high probability at 30 days (0.1% vs. 0.5% and 1.8%) and 1 year (0.3% vs. 2.8% and 4.2%).

“The results show that the machine learning model doubles the proportion of patients who can be discharged with a single test compared to the current practice of using the threshold approach. It really is a game changer in terms of its potential to improve health efficiency,” Dr. Mills said.

In terms of ruling patients in as possibly having an MI, he pointed out that troponin levels are increased in patients with a wide range of other conditions, including heart failure, kidney failure, and atrial fibrillation.

“When using the threshold approach, only one in four patients with an elevated troponin level will actually be having an MI, and that leads to confusion,” he said. “This model takes into consideration these other conditions and so it can correctly identify three out of four patients with a high probability of having an MI. We can therefore be more confident that it is appropriate to refer those patients to cardiology and save a lot of potentially unnecessary investigations and treatments in the others.”

Dr. Mills said the model also seems to work when assessing patients early on.

“Around one-third of patients present within 3 hours of symptom onset, and actually these are a high-risk group because people who have genuine cardiac pain are normally extremely uncomfortable and tend to present quickly. Current guidelines require that we do two tests in all these individuals, but this new model incorporates the time of symptom onset into its estimates of probability and therefore allows us to rule out patients even when they present very early.”

He reported that a second test is required in only one in five patients – those whose first test indicated intermediate probability.

“The second test allows us to refine the probability further, allowing us to rule another half of those patients out. We are then left with a small proportion of patients – about 1 in 10 – who remain of intermediate probability and will require additional clinical judgment.”
 

Should improve inequities in MI diagnosis

Dr. Mills said the CoDE-ACS model will improve current inequities in MI diagnosis, because of which MI is underrecognized in women and younger people.

“Women have troponin concentrations that are half those of men, and although sex-specific troponin thresholds are recommended in the guidelines, they are not widely used. This automatically leads to underrecognition of heart disease in women. But this new machine learning model performs identically in men and women because it has been trained to recognize the different normal levels in men and women,” he explained.

“It will also help us not to underdiagnose MI in younger people who often have a less classical presentation of MI, and they also generally have very low concentrations of troponin, so any increase in troponin way below the current diagnostic threshold may be very relevant to their risk,” he added.

The researchers are planning a randomized trial of the new model to demonstrate the impact it could have on equality of care and overcrowding in the emergency department. In the trial, patients will be randomly assigned to undergo decision-making on the basis of troponin thresholds (current practice) or to undergo decision-making through the CoDE-ACS model.

“The hope is that this trial will show reductions in unnecessary hospital admissions and length of stay in the emergency department,” Dr. Mills said. Results are expected sometime next year.

“This algorithm is very well trained. It has learned on 20,000 patients, so it has a lot more experience than I have, and I have been a professor of cardiology for 20 years,” Dr. Mills said.

He said he believes these models will get even smarter in the future as more data are added.

“I think the future for good decision-making in emergency care will be informed by clinical decision support from well-trained machine learning algorithms and they will help us guide not just the diagnosis of MI but also heart failure and other important cardiac conditions,” he said.
 

‘Elegant and exciting’ data

Commenting on the study, John W. McEvoy, MB, University of Galway, Ireland, said: “These are elegant and exciting data; however, the inputs into the machine learning algorithm include all the necessary information to actually diagnose MI. So why predict MI, when a human diagnosis can just be made directly? The answer to this question may depend on whether we trust machines more than humans.”

Dr. Mills noted that clinical judgment will always be an important part of MI diagnosis.

“Currently, using the troponin threshold approach, experienced clinicians will be able to nuance the results, but invariably, there is disagreement on this, and this can be a major source of tension within clinical care. By providing more individualized information, this will help enormously in the decision-making process,” he said.

“This model is not about replacing clinical decision-making. It’s more about augmenting decision-making and giving clinicians guidance to be able to improve efficiency and reduce inequality,” he added.

The study was funded with support from the National Institute for Health Research and NHSX, the British Heart Foundation, and Wellcome Leap. Dr. Mills has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. He is employed by the University of Edinburgh, which has filed a patent on the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome score.
 

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

Use of a machine-learning model that incorporates information from a single troponin test as well as other clinical data was superior to current practice as an aid to the diagnosis of myocardial infarction in the emergency department in a new study.

“Our results suggest that by using this machine-learning model, compared to the currently recommended approach, we could double the proportion of patients who are identified correctly as having a low probability of an MI on arrival to enable immediate discharge and free up space in the emergency department,” senior author Nicholas L. Mills, MD, University of Edinburgh, Scotland, said in an interview.

“And, perhaps even more importantly, use of this model could also increase the proportion of patients who are correctly identified as at a high probability of having an MI,” he added.

The study was published online in Nature Medicine.

The authors explained that at present, the likelihood of an MI diagnosis for patients presenting to the emergency department with chest pain is based on a fixed troponin threshold in serial tests at specific time points, but there are several problems with this approach.

First, a fixed troponin threshold is generally used for all patients, which does not account for age, sex, or comorbidities that are known to influence cardiac troponin concentrations. Second, the need to perform tests at specific time points for serial testing can be challenging in busy emergency departments.

And third, patients are categorized as being at low, intermediate, or high risk of MI on the basis of troponin thresholds alone, and the test does not take into account other important factors, such as the time of symptom onset or findings on the electrocardiogram.

“Our current practice of using the same threshold to rule in and rule out an MI for everyone, regardless of whether they are an 18-year-old female without a history of heart disease or an 85-year-old male with known heart failure, doesn’t perform well, and there’s a significant risk of misdiagnosis. There is also a high likelihood for inequalities in care, particularly between men and women,” Dr. Mills said.

The current study evaluated whether use of a machine learning model known as CoDE-ACS to guide decision-making could overcome some of these challenges.

The machine learning model assesses the whole spectrum of troponin levels as a continuous variable (rather than use of a single threshold) and turns this measurement into a probability that an individual patient is having an MI after accounting for other factors, including age, sex, comorbidities, and time from symptom onset.

For the current study, the CoDE-ACS model was trained in 10,000 patients with suspected acute coronary syndrome (ACS) who presented to 10 hospitals in Scotland as part of the High-STEACS trial evaluating the implementation of a high-sensitivity cardiac troponin I assay. The results were then validated in another 10,000 patients from six countries around the world.

“Using this model, the patient can have a troponin test on arrival at the emergency department. The other information on age, sex, clinical history, and time since symptom onset is keyed in, and it gives a probability on a scale of 0–100 as to whether the patient is having an MI,” Dr. Mills noted.

“It also has the capacity to incorporate more information over time. So, if there is a second troponin measurement made, then the model automatically refines the probability score,” he added.

The current study showed that use of the CoDE-ACS model identified more patients at presentation as having a low probability of having an MI than fixed cardiac troponin thresholds (61% vs. 27%) with a similar negative predictive value.

It also identified fewer patients as having a high probability of having an MI (10% vs. 16%) with a greater positive predictive value.

Among patients who were identified as having a low probability of MI, the rate of cardiac death was lower than the rate among those with intermediate or high probability at 30 days (0.1% vs. 0.5% and 1.8%) and 1 year (0.3% vs. 2.8% and 4.2%).

“The results show that the machine learning model doubles the proportion of patients who can be discharged with a single test compared to the current practice of using the threshold approach. It really is a game changer in terms of its potential to improve health efficiency,” Dr. Mills said.

In terms of ruling patients in as possibly having an MI, he pointed out that troponin levels are increased in patients with a wide range of other conditions, including heart failure, kidney failure, and atrial fibrillation.

“When using the threshold approach, only one in four patients with an elevated troponin level will actually be having an MI, and that leads to confusion,” he said. “This model takes into consideration these other conditions and so it can correctly identify three out of four patients with a high probability of having an MI. We can therefore be more confident that it is appropriate to refer those patients to cardiology and save a lot of potentially unnecessary investigations and treatments in the others.”

Dr. Mills said the model also seems to work when assessing patients early on.

“Around one-third of patients present within 3 hours of symptom onset, and actually these are a high-risk group because people who have genuine cardiac pain are normally extremely uncomfortable and tend to present quickly. Current guidelines require that we do two tests in all these individuals, but this new model incorporates the time of symptom onset into its estimates of probability and therefore allows us to rule out patients even when they present very early.”

He reported that a second test is required in only one in five patients – those whose first test indicated intermediate probability.

“The second test allows us to refine the probability further, allowing us to rule another half of those patients out. We are then left with a small proportion of patients – about 1 in 10 – who remain of intermediate probability and will require additional clinical judgment.”
 

Should improve inequities in MI diagnosis

Dr. Mills said the CoDE-ACS model will improve current inequities in MI diagnosis, because of which MI is underrecognized in women and younger people.

“Women have troponin concentrations that are half those of men, and although sex-specific troponin thresholds are recommended in the guidelines, they are not widely used. This automatically leads to underrecognition of heart disease in women. But this new machine learning model performs identically in men and women because it has been trained to recognize the different normal levels in men and women,” he explained.

“It will also help us not to underdiagnose MI in younger people who often have a less classical presentation of MI, and they also generally have very low concentrations of troponin, so any increase in troponin way below the current diagnostic threshold may be very relevant to their risk,” he added.

The researchers are planning a randomized trial of the new model to demonstrate the impact it could have on equality of care and overcrowding in the emergency department. In the trial, patients will be randomly assigned to undergo decision-making on the basis of troponin thresholds (current practice) or to undergo decision-making through the CoDE-ACS model.

“The hope is that this trial will show reductions in unnecessary hospital admissions and length of stay in the emergency department,” Dr. Mills said. Results are expected sometime next year.

“This algorithm is very well trained. It has learned on 20,000 patients, so it has a lot more experience than I have, and I have been a professor of cardiology for 20 years,” Dr. Mills said.

He said he believes these models will get even smarter in the future as more data are added.

“I think the future for good decision-making in emergency care will be informed by clinical decision support from well-trained machine learning algorithms and they will help us guide not just the diagnosis of MI but also heart failure and other important cardiac conditions,” he said.
 

‘Elegant and exciting’ data

Commenting on the study, John W. McEvoy, MB, University of Galway, Ireland, said: “These are elegant and exciting data; however, the inputs into the machine learning algorithm include all the necessary information to actually diagnose MI. So why predict MI, when a human diagnosis can just be made directly? The answer to this question may depend on whether we trust machines more than humans.”

Dr. Mills noted that clinical judgment will always be an important part of MI diagnosis.

“Currently, using the troponin threshold approach, experienced clinicians will be able to nuance the results, but invariably, there is disagreement on this, and this can be a major source of tension within clinical care. By providing more individualized information, this will help enormously in the decision-making process,” he said.

“This model is not about replacing clinical decision-making. It’s more about augmenting decision-making and giving clinicians guidance to be able to improve efficiency and reduce inequality,” he added.

The study was funded with support from the National Institute for Health Research and NHSX, the British Heart Foundation, and Wellcome Leap. Dr. Mills has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. He is employed by the University of Edinburgh, which has filed a patent on the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome score.
 

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

Use of a machine-learning model that incorporates information from a single troponin test as well as other clinical data was superior to current practice as an aid to the diagnosis of myocardial infarction in the emergency department in a new study.

“Our results suggest that by using this machine-learning model, compared to the currently recommended approach, we could double the proportion of patients who are identified correctly as having a low probability of an MI on arrival to enable immediate discharge and free up space in the emergency department,” senior author Nicholas L. Mills, MD, University of Edinburgh, Scotland, said in an interview.

“And, perhaps even more importantly, use of this model could also increase the proportion of patients who are correctly identified as at a high probability of having an MI,” he added.

The study was published online in Nature Medicine.

The authors explained that at present, the likelihood of an MI diagnosis for patients presenting to the emergency department with chest pain is based on a fixed troponin threshold in serial tests at specific time points, but there are several problems with this approach.

First, a fixed troponin threshold is generally used for all patients, which does not account for age, sex, or comorbidities that are known to influence cardiac troponin concentrations. Second, the need to perform tests at specific time points for serial testing can be challenging in busy emergency departments.

And third, patients are categorized as being at low, intermediate, or high risk of MI on the basis of troponin thresholds alone, and the test does not take into account other important factors, such as the time of symptom onset or findings on the electrocardiogram.

“Our current practice of using the same threshold to rule in and rule out an MI for everyone, regardless of whether they are an 18-year-old female without a history of heart disease or an 85-year-old male with known heart failure, doesn’t perform well, and there’s a significant risk of misdiagnosis. There is also a high likelihood for inequalities in care, particularly between men and women,” Dr. Mills said.

The current study evaluated whether use of a machine learning model known as CoDE-ACS to guide decision-making could overcome some of these challenges.

The machine learning model assesses the whole spectrum of troponin levels as a continuous variable (rather than use of a single threshold) and turns this measurement into a probability that an individual patient is having an MI after accounting for other factors, including age, sex, comorbidities, and time from symptom onset.

For the current study, the CoDE-ACS model was trained in 10,000 patients with suspected acute coronary syndrome (ACS) who presented to 10 hospitals in Scotland as part of the High-STEACS trial evaluating the implementation of a high-sensitivity cardiac troponin I assay. The results were then validated in another 10,000 patients from six countries around the world.

“Using this model, the patient can have a troponin test on arrival at the emergency department. The other information on age, sex, clinical history, and time since symptom onset is keyed in, and it gives a probability on a scale of 0–100 as to whether the patient is having an MI,” Dr. Mills noted.

“It also has the capacity to incorporate more information over time. So, if there is a second troponin measurement made, then the model automatically refines the probability score,” he added.

The current study showed that use of the CoDE-ACS model identified more patients at presentation as having a low probability of having an MI than fixed cardiac troponin thresholds (61% vs. 27%) with a similar negative predictive value.

It also identified fewer patients as having a high probability of having an MI (10% vs. 16%) with a greater positive predictive value.

Among patients who were identified as having a low probability of MI, the rate of cardiac death was lower than the rate among those with intermediate or high probability at 30 days (0.1% vs. 0.5% and 1.8%) and 1 year (0.3% vs. 2.8% and 4.2%).

“The results show that the machine learning model doubles the proportion of patients who can be discharged with a single test compared to the current practice of using the threshold approach. It really is a game changer in terms of its potential to improve health efficiency,” Dr. Mills said.

In terms of ruling patients in as possibly having an MI, he pointed out that troponin levels are increased in patients with a wide range of other conditions, including heart failure, kidney failure, and atrial fibrillation.

“When using the threshold approach, only one in four patients with an elevated troponin level will actually be having an MI, and that leads to confusion,” he said. “This model takes into consideration these other conditions and so it can correctly identify three out of four patients with a high probability of having an MI. We can therefore be more confident that it is appropriate to refer those patients to cardiology and save a lot of potentially unnecessary investigations and treatments in the others.”

Dr. Mills said the model also seems to work when assessing patients early on.

“Around one-third of patients present within 3 hours of symptom onset, and actually these are a high-risk group because people who have genuine cardiac pain are normally extremely uncomfortable and tend to present quickly. Current guidelines require that we do two tests in all these individuals, but this new model incorporates the time of symptom onset into its estimates of probability and therefore allows us to rule out patients even when they present very early.”

He reported that a second test is required in only one in five patients – those whose first test indicated intermediate probability.

“The second test allows us to refine the probability further, allowing us to rule another half of those patients out. We are then left with a small proportion of patients – about 1 in 10 – who remain of intermediate probability and will require additional clinical judgment.”
 

Should improve inequities in MI diagnosis

Dr. Mills said the CoDE-ACS model will improve current inequities in MI diagnosis, because of which MI is underrecognized in women and younger people.

“Women have troponin concentrations that are half those of men, and although sex-specific troponin thresholds are recommended in the guidelines, they are not widely used. This automatically leads to underrecognition of heart disease in women. But this new machine learning model performs identically in men and women because it has been trained to recognize the different normal levels in men and women,” he explained.

“It will also help us not to underdiagnose MI in younger people who often have a less classical presentation of MI, and they also generally have very low concentrations of troponin, so any increase in troponin way below the current diagnostic threshold may be very relevant to their risk,” he added.

The researchers are planning a randomized trial of the new model to demonstrate the impact it could have on equality of care and overcrowding in the emergency department. In the trial, patients will be randomly assigned to undergo decision-making on the basis of troponin thresholds (current practice) or to undergo decision-making through the CoDE-ACS model.

“The hope is that this trial will show reductions in unnecessary hospital admissions and length of stay in the emergency department,” Dr. Mills said. Results are expected sometime next year.

“This algorithm is very well trained. It has learned on 20,000 patients, so it has a lot more experience than I have, and I have been a professor of cardiology for 20 years,” Dr. Mills said.

He said he believes these models will get even smarter in the future as more data are added.

“I think the future for good decision-making in emergency care will be informed by clinical decision support from well-trained machine learning algorithms and they will help us guide not just the diagnosis of MI but also heart failure and other important cardiac conditions,” he said.
 

‘Elegant and exciting’ data

Commenting on the study, John W. McEvoy, MB, University of Galway, Ireland, said: “These are elegant and exciting data; however, the inputs into the machine learning algorithm include all the necessary information to actually diagnose MI. So why predict MI, when a human diagnosis can just be made directly? The answer to this question may depend on whether we trust machines more than humans.”

Dr. Mills noted that clinical judgment will always be an important part of MI diagnosis.

“Currently, using the troponin threshold approach, experienced clinicians will be able to nuance the results, but invariably, there is disagreement on this, and this can be a major source of tension within clinical care. By providing more individualized information, this will help enormously in the decision-making process,” he said.

“This model is not about replacing clinical decision-making. It’s more about augmenting decision-making and giving clinicians guidance to be able to improve efficiency and reduce inequality,” he added.

The study was funded with support from the National Institute for Health Research and NHSX, the British Heart Foundation, and Wellcome Leap. Dr. Mills has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. He is employed by the University of Edinburgh, which has filed a patent on the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome score.
 

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

Anticipating Food and Drug Administration approval of at least one investigational device for renal denervation (RDN) as a treatment for hypertension (HTN) refractory to medical therapies, the Society for Cardiovascular Angiography and Interventions is asking its members and the public to provide input on a draft position statement to guide use of the procedure.

The draft addresses appropriate patient selection, best practices for procedural techniques, measures for operator competence, recommendations for operator and staff training, and guidance for hospitals and centers that want to adopt RDN. SCAI is requesting feedback by June 14.

“With the anticipated FDA approval of renal denervation, there will be a need for SCAI to formulate an official position around clinical competence and training standards, best practices, and institutional and operator requirements for RDN,” Herbert D. Aronow, MD, MPH, chair of the statement writing committee, said in an interview.

RDN is an endoscopic procedure that disrupts the sympathetic nerves near the renal arteries. A number of studies, including sham-controlled, randomized trials, have shown that RDN can achieve short-term reductions in blood pressure for patients for whom HTN medications don’t work. Two devices are awaiting FDA premarket approval: the Paradise uRDN system, by ReCor Medical; and the Symplicity Spyral device, by Medtronic.

However, the trajectory of RDN has been uneven, said Dr. Aronow, president of the Society for Vascular Medicine and medical director for heart and vascular services and Benson Ford Chair in cardiology at Henry Ford Health, Detroit.

“Despite supportive early animal and human data, the first sham-controlled randomized trial of RDN was negative on its primary endpoint,” he said. “Modifications to patient inclusion/exclusion criteria, refinements in denervation technology and protocols, and selection of more appropriate study endpoints resulted in a series of positive randomized, sham-controlled trials. These second-generation trials found that RDN, when compared with sham therapy, substantially reduced ambulatory and office blood pressures.”

The draft is available for review at the SCAI website. Comments may be submitted via a link to a questionnaire.

“Through the open comment process, we are hoping to gain broad perspective from stakeholders, including clinicians, hospitals, payers, professional societies, industry and patients,” Dr. Aronow said. “By incorporating this feedback, we hope to enhance the quality of the document before we submit it for publication.”

The bulk of the SCAI draft position statement is devoted to patient selection and procedural and technical considerations. “We believe it will serve as a road map for the successful launch of RDN programs around the United States,” Dr. Aronow said.
 

Patient selection considerations

The draft statement notes that RDN for all patients with uncontrolled HTN “would not currently be practical.” The average age of patients for whom RDN showed effectiveness in the cited clinical trials was less than 60 years. The effectiveness of RDN for patients in whom arterial stiffness is a primary driver of HTN “is less certain.”

Patients who may benefit most from RDN are those with limited medical treatment options. Initially, RDN was tried on patients who had continued to experience resistant HTN despite taking three or more medications, including a diuretic, the statement noted. But even nonadherent patients may derive some potential benefit from RDN.

The statement also added that RDN isn’t a panacea; about one-third of trial patients didn’t respond to the procedure. The most reliable predictor of response may be higher levels of baseline systolic blood pressure, otherwise known as Wilder’s principle. The statement listed other potential markers of success, including higher nocturnal blood pressure and wider swings in nocturnal blood pressure.
 

Procedural and technical considerations

The statement also provided direction on a protocol for RDN procedures. The preprocedure evaluation should include noninvasive imaging to rule out disqualifying secondary causes of HTN, such as renal artery stenosis or fibromuscular dysplasia.

Patient characteristics should drive the selection of imaging modality, and availability as well as local expertise should be taken into account. The statement gave CT angiography or magnetic resonance angiography the edge over duplex ultrasound.

The statement also noted a number of anatomic considerations, citing preclinical analyses that “consistently reinforce” circumferential, perivascular RDN to ablate the renal nerves. In planning the procedure, consideration should be given to accessory renal arteries.

Additionally, operators should have training in obtaining access, and they should be familiar with different catheters and console devices as well as troubleshooting.
 

Training, competency, and institutional requirements

Interventional cardiologists who want to perform RDN should demonstrate proficiency in a number of specific skill sets germane to the procedure, from arterial vascular access and hemostasis to recognizing and treating potential renovascular complications.

For institutions that want to offer RDN, the statement offered a number of requirements. One is to designate a primary physician stakeholder who’s well versed in HTN management to oversee the long-term management of RDN patients.

The institution must have a dedicated HTN program and a multidisciplinary team to manage treated patients. Requirements for RDN referral centers range from operators experienced with FDA-approved RDN devices to an infrastructure that includes CT or MR angiography to identify appropriate candidates.

“Renal denervation has been a long time coming, and it’s a great example of how academicians, clinicians and industry leaders can partner to move the cardiovascular field forward, addressing a major public health issue for which alternative solutions are greatly needed,” Dr. Aronow said.

Dr. Aronow has served as an unpaid council member for Medtronic and as a paid moderator for ReCor.

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

Anticipating Food and Drug Administration approval of at least one investigational device for renal denervation (RDN) as a treatment for hypertension (HTN) refractory to medical therapies, the Society for Cardiovascular Angiography and Interventions is asking its members and the public to provide input on a draft position statement to guide use of the procedure.

The draft addresses appropriate patient selection, best practices for procedural techniques, measures for operator competence, recommendations for operator and staff training, and guidance for hospitals and centers that want to adopt RDN. SCAI is requesting feedback by June 14.

“With the anticipated FDA approval of renal denervation, there will be a need for SCAI to formulate an official position around clinical competence and training standards, best practices, and institutional and operator requirements for RDN,” Herbert D. Aronow, MD, MPH, chair of the statement writing committee, said in an interview.

RDN is an endoscopic procedure that disrupts the sympathetic nerves near the renal arteries. A number of studies, including sham-controlled, randomized trials, have shown that RDN can achieve short-term reductions in blood pressure for patients for whom HTN medications don’t work. Two devices are awaiting FDA premarket approval: the Paradise uRDN system, by ReCor Medical; and the Symplicity Spyral device, by Medtronic.

However, the trajectory of RDN has been uneven, said Dr. Aronow, president of the Society for Vascular Medicine and medical director for heart and vascular services and Benson Ford Chair in cardiology at Henry Ford Health, Detroit.

“Despite supportive early animal and human data, the first sham-controlled randomized trial of RDN was negative on its primary endpoint,” he said. “Modifications to patient inclusion/exclusion criteria, refinements in denervation technology and protocols, and selection of more appropriate study endpoints resulted in a series of positive randomized, sham-controlled trials. These second-generation trials found that RDN, when compared with sham therapy, substantially reduced ambulatory and office blood pressures.”

The draft is available for review at the SCAI website. Comments may be submitted via a link to a questionnaire.

“Through the open comment process, we are hoping to gain broad perspective from stakeholders, including clinicians, hospitals, payers, professional societies, industry and patients,” Dr. Aronow said. “By incorporating this feedback, we hope to enhance the quality of the document before we submit it for publication.”

The bulk of the SCAI draft position statement is devoted to patient selection and procedural and technical considerations. “We believe it will serve as a road map for the successful launch of RDN programs around the United States,” Dr. Aronow said.
 

Patient selection considerations

The draft statement notes that RDN for all patients with uncontrolled HTN “would not currently be practical.” The average age of patients for whom RDN showed effectiveness in the cited clinical trials was less than 60 years. The effectiveness of RDN for patients in whom arterial stiffness is a primary driver of HTN “is less certain.”

Patients who may benefit most from RDN are those with limited medical treatment options. Initially, RDN was tried on patients who had continued to experience resistant HTN despite taking three or more medications, including a diuretic, the statement noted. But even nonadherent patients may derive some potential benefit from RDN.

The statement also added that RDN isn’t a panacea; about one-third of trial patients didn’t respond to the procedure. The most reliable predictor of response may be higher levels of baseline systolic blood pressure, otherwise known as Wilder’s principle. The statement listed other potential markers of success, including higher nocturnal blood pressure and wider swings in nocturnal blood pressure.
 

Procedural and technical considerations

The statement also provided direction on a protocol for RDN procedures. The preprocedure evaluation should include noninvasive imaging to rule out disqualifying secondary causes of HTN, such as renal artery stenosis or fibromuscular dysplasia.

Patient characteristics should drive the selection of imaging modality, and availability as well as local expertise should be taken into account. The statement gave CT angiography or magnetic resonance angiography the edge over duplex ultrasound.

The statement also noted a number of anatomic considerations, citing preclinical analyses that “consistently reinforce” circumferential, perivascular RDN to ablate the renal nerves. In planning the procedure, consideration should be given to accessory renal arteries.

Additionally, operators should have training in obtaining access, and they should be familiar with different catheters and console devices as well as troubleshooting.
 

Training, competency, and institutional requirements

Interventional cardiologists who want to perform RDN should demonstrate proficiency in a number of specific skill sets germane to the procedure, from arterial vascular access and hemostasis to recognizing and treating potential renovascular complications.

For institutions that want to offer RDN, the statement offered a number of requirements. One is to designate a primary physician stakeholder who’s well versed in HTN management to oversee the long-term management of RDN patients.

The institution must have a dedicated HTN program and a multidisciplinary team to manage treated patients. Requirements for RDN referral centers range from operators experienced with FDA-approved RDN devices to an infrastructure that includes CT or MR angiography to identify appropriate candidates.

“Renal denervation has been a long time coming, and it’s a great example of how academicians, clinicians and industry leaders can partner to move the cardiovascular field forward, addressing a major public health issue for which alternative solutions are greatly needed,” Dr. Aronow said.

Dr. Aronow has served as an unpaid council member for Medtronic and as a paid moderator for ReCor.

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

Anticipating Food and Drug Administration approval of at least one investigational device for renal denervation (RDN) as a treatment for hypertension (HTN) refractory to medical therapies, the Society for Cardiovascular Angiography and Interventions is asking its members and the public to provide input on a draft position statement to guide use of the procedure.

The draft addresses appropriate patient selection, best practices for procedural techniques, measures for operator competence, recommendations for operator and staff training, and guidance for hospitals and centers that want to adopt RDN. SCAI is requesting feedback by June 14.

“With the anticipated FDA approval of renal denervation, there will be a need for SCAI to formulate an official position around clinical competence and training standards, best practices, and institutional and operator requirements for RDN,” Herbert D. Aronow, MD, MPH, chair of the statement writing committee, said in an interview.

RDN is an endoscopic procedure that disrupts the sympathetic nerves near the renal arteries. A number of studies, including sham-controlled, randomized trials, have shown that RDN can achieve short-term reductions in blood pressure for patients for whom HTN medications don’t work. Two devices are awaiting FDA premarket approval: the Paradise uRDN system, by ReCor Medical; and the Symplicity Spyral device, by Medtronic.

However, the trajectory of RDN has been uneven, said Dr. Aronow, president of the Society for Vascular Medicine and medical director for heart and vascular services and Benson Ford Chair in cardiology at Henry Ford Health, Detroit.

“Despite supportive early animal and human data, the first sham-controlled randomized trial of RDN was negative on its primary endpoint,” he said. “Modifications to patient inclusion/exclusion criteria, refinements in denervation technology and protocols, and selection of more appropriate study endpoints resulted in a series of positive randomized, sham-controlled trials. These second-generation trials found that RDN, when compared with sham therapy, substantially reduced ambulatory and office blood pressures.”

The draft is available for review at the SCAI website. Comments may be submitted via a link to a questionnaire.

“Through the open comment process, we are hoping to gain broad perspective from stakeholders, including clinicians, hospitals, payers, professional societies, industry and patients,” Dr. Aronow said. “By incorporating this feedback, we hope to enhance the quality of the document before we submit it for publication.”

The bulk of the SCAI draft position statement is devoted to patient selection and procedural and technical considerations. “We believe it will serve as a road map for the successful launch of RDN programs around the United States,” Dr. Aronow said.
 

Patient selection considerations

The draft statement notes that RDN for all patients with uncontrolled HTN “would not currently be practical.” The average age of patients for whom RDN showed effectiveness in the cited clinical trials was less than 60 years. The effectiveness of RDN for patients in whom arterial stiffness is a primary driver of HTN “is less certain.”

Patients who may benefit most from RDN are those with limited medical treatment options. Initially, RDN was tried on patients who had continued to experience resistant HTN despite taking three or more medications, including a diuretic, the statement noted. But even nonadherent patients may derive some potential benefit from RDN.

The statement also added that RDN isn’t a panacea; about one-third of trial patients didn’t respond to the procedure. The most reliable predictor of response may be higher levels of baseline systolic blood pressure, otherwise known as Wilder’s principle. The statement listed other potential markers of success, including higher nocturnal blood pressure and wider swings in nocturnal blood pressure.
 

Procedural and technical considerations

The statement also provided direction on a protocol for RDN procedures. The preprocedure evaluation should include noninvasive imaging to rule out disqualifying secondary causes of HTN, such as renal artery stenosis or fibromuscular dysplasia.

Patient characteristics should drive the selection of imaging modality, and availability as well as local expertise should be taken into account. The statement gave CT angiography or magnetic resonance angiography the edge over duplex ultrasound.

The statement also noted a number of anatomic considerations, citing preclinical analyses that “consistently reinforce” circumferential, perivascular RDN to ablate the renal nerves. In planning the procedure, consideration should be given to accessory renal arteries.

Additionally, operators should have training in obtaining access, and they should be familiar with different catheters and console devices as well as troubleshooting.
 

Training, competency, and institutional requirements

Interventional cardiologists who want to perform RDN should demonstrate proficiency in a number of specific skill sets germane to the procedure, from arterial vascular access and hemostasis to recognizing and treating potential renovascular complications.

For institutions that want to offer RDN, the statement offered a number of requirements. One is to designate a primary physician stakeholder who’s well versed in HTN management to oversee the long-term management of RDN patients.

The institution must have a dedicated HTN program and a multidisciplinary team to manage treated patients. Requirements for RDN referral centers range from operators experienced with FDA-approved RDN devices to an infrastructure that includes CT or MR angiography to identify appropriate candidates.

“Renal denervation has been a long time coming, and it’s a great example of how academicians, clinicians and industry leaders can partner to move the cardiovascular field forward, addressing a major public health issue for which alternative solutions are greatly needed,” Dr. Aronow said.

Dr. Aronow has served as an unpaid council member for Medtronic and as a paid moderator for ReCor.

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

PHOENIX – Marijuana users have an almost four times greater risk of developing peripheral artery disease, compared with nonusers, results of a study of more than 600,000 marijuana users suggest, although there was no greater risk of death from myocardial infarction or other cardiac causes or need for revascularization.

Instants/Getty Images

The researchers noted, however, that the study population was young, with an average age of 37.4 years, and that the study period, from 2016 to 2019, predates the legalization of recreational marijuana in a number of states.

Nonetheless, even in this young study population, marijuana users’ risk of developing peripheral artery disease (PAD) was 3.68 times greater (P < .001) than that of nonusers. PAD at a young age could precede worse outcomes later in life, the study authors said.

“Basically, marijuana users were at increased risk of being diagnosed with peripheral artery disease, but there was no increased risk for them requiring any intervention, such as a peripheral vascular intervention, nor were they at increased risk of death from what we found,” said Hirva Vyas, DO, an internal medicine resident at Hackensack University Medical Center in New Jersey, who presented the results at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The study used data on 623,768 marijuana users from the National Inpatient Sample, a nationwide database of inpatient visits covered by all public and commercial payers, then extracted a diagnosis for PAD from all 30 million–plus patient encounters to compare PAD rates between marijuana users and nonusers. Marijuana users were more likely to be White and to have elective rather than emergency admissions (P < .001). The researchers used diagnostic codes to identify marijuana users and PAD patients.

Recreational marijuana is legal in 22 states and the District of Columbia, according to ProCon.org. Since 2019, the last year of the study, 11 states have legalized marijuana for recreational use. “It’s a data point that we studied at one point in time, only from 2016 to 2019,” Dr. Vyas said in an interview.

“As we’ve seen over the past 4-5 years, legalization has skyrocketed and recreational use has become more and more favorable not only among younger folks but older folks,” study coauthor Harsh Jain, MD, a second-year internal medicine resident at Montefiore Medical Center in New York, said in the interview. “It would be really refreshing to see how these data change as we look at endpoints from 2019 to 2023.”

Because of the young age of the study population, Dr. Jain said, these findings may not accurately represent the true cardiovascular risks of marijuana use, especially later in life.

“One of the biggest secondary endpoints that we wanted to study was the development of chronic conditions that lead to multiple rehospitalizations, the most significant one of which would be the development of heart failure,” Dr. Jain said. “However, it was difficult to stratify because, again, many of these patients were very young and so they did not carry the diagnosis for heart failure, so we couldn’t complete that subset analysis.”

The goal is to extend the study period out to 2023, Dr. Jain said. “We know that these are very crude and rudimentary data findings that we presented so far, but we’re hoping that the final paper gives us a chance to flesh out all the details of our study and also gives us a chance to expand going forward,” he said.

The findings are in line with other research into the effects of marijuana and cardiovascular disease, said Carl “Chip” Lavie, MD, medical director for cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute in New Orleans who’s published a number of studies on PAD and substance use, including marijuana.

“It is known that cannabis is associated with more vasoconstriction, has sympathomimetic effects, causes endothelial dysfunction and increased platelet aggregation, and is known to increase the risk of acute myocardial infarction, especially in the hour or so after use,” he said in written comments sent to this news organization.

“It is also well known to be a cause of thromboangiitis obliterans, which is in the PAD family,” he added. “Based on these mechanisms, one would expect an increased PAD and, especially, PAD events. The 3.7-fold increased risk is supportive of this increased PAD.”

One study strength, Dr. Lavie pointed out, is that it’s one of the few studies that found an association between marijuana and PAD, which hasn’t been studied as well as other cardiovascular endpoints. “However,” he said, “the limitation is this is just an inpatient sample, and it is all based on coding – e.g., a patient could have PAD and it may not have been coded.”

PHOENIX – Marijuana users have an almost four times greater risk of developing peripheral artery disease, compared with nonusers, results of a study of more than 600,000 marijuana users suggest, although there was no greater risk of death from myocardial infarction or other cardiac causes or need for revascularization.

Instants/Getty Images

The researchers noted, however, that the study population was young, with an average age of 37.4 years, and that the study period, from 2016 to 2019, predates the legalization of recreational marijuana in a number of states.

Nonetheless, even in this young study population, marijuana users’ risk of developing peripheral artery disease (PAD) was 3.68 times greater (P < .001) than that of nonusers. PAD at a young age could precede worse outcomes later in life, the study authors said.

“Basically, marijuana users were at increased risk of being diagnosed with peripheral artery disease, but there was no increased risk for them requiring any intervention, such as a peripheral vascular intervention, nor were they at increased risk of death from what we found,” said Hirva Vyas, DO, an internal medicine resident at Hackensack University Medical Center in New Jersey, who presented the results at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The study used data on 623,768 marijuana users from the National Inpatient Sample, a nationwide database of inpatient visits covered by all public and commercial payers, then extracted a diagnosis for PAD from all 30 million–plus patient encounters to compare PAD rates between marijuana users and nonusers. Marijuana users were more likely to be White and to have elective rather than emergency admissions (P < .001). The researchers used diagnostic codes to identify marijuana users and PAD patients.

Recreational marijuana is legal in 22 states and the District of Columbia, according to ProCon.org. Since 2019, the last year of the study, 11 states have legalized marijuana for recreational use. “It’s a data point that we studied at one point in time, only from 2016 to 2019,” Dr. Vyas said in an interview.

“As we’ve seen over the past 4-5 years, legalization has skyrocketed and recreational use has become more and more favorable not only among younger folks but older folks,” study coauthor Harsh Jain, MD, a second-year internal medicine resident at Montefiore Medical Center in New York, said in the interview. “It would be really refreshing to see how these data change as we look at endpoints from 2019 to 2023.”

Because of the young age of the study population, Dr. Jain said, these findings may not accurately represent the true cardiovascular risks of marijuana use, especially later in life.

“One of the biggest secondary endpoints that we wanted to study was the development of chronic conditions that lead to multiple rehospitalizations, the most significant one of which would be the development of heart failure,” Dr. Jain said. “However, it was difficult to stratify because, again, many of these patients were very young and so they did not carry the diagnosis for heart failure, so we couldn’t complete that subset analysis.”

The goal is to extend the study period out to 2023, Dr. Jain said. “We know that these are very crude and rudimentary data findings that we presented so far, but we’re hoping that the final paper gives us a chance to flesh out all the details of our study and also gives us a chance to expand going forward,” he said.

The findings are in line with other research into the effects of marijuana and cardiovascular disease, said Carl “Chip” Lavie, MD, medical director for cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute in New Orleans who’s published a number of studies on PAD and substance use, including marijuana.

“It is known that cannabis is associated with more vasoconstriction, has sympathomimetic effects, causes endothelial dysfunction and increased platelet aggregation, and is known to increase the risk of acute myocardial infarction, especially in the hour or so after use,” he said in written comments sent to this news organization.

“It is also well known to be a cause of thromboangiitis obliterans, which is in the PAD family,” he added. “Based on these mechanisms, one would expect an increased PAD and, especially, PAD events. The 3.7-fold increased risk is supportive of this increased PAD.”

One study strength, Dr. Lavie pointed out, is that it’s one of the few studies that found an association between marijuana and PAD, which hasn’t been studied as well as other cardiovascular endpoints. “However,” he said, “the limitation is this is just an inpatient sample, and it is all based on coding – e.g., a patient could have PAD and it may not have been coded.”

PHOENIX – Marijuana users have an almost four times greater risk of developing peripheral artery disease, compared with nonusers, results of a study of more than 600,000 marijuana users suggest, although there was no greater risk of death from myocardial infarction or other cardiac causes or need for revascularization.

Instants/Getty Images

The researchers noted, however, that the study population was young, with an average age of 37.4 years, and that the study period, from 2016 to 2019, predates the legalization of recreational marijuana in a number of states.

Nonetheless, even in this young study population, marijuana users’ risk of developing peripheral artery disease (PAD) was 3.68 times greater (P < .001) than that of nonusers. PAD at a young age could precede worse outcomes later in life, the study authors said.

“Basically, marijuana users were at increased risk of being diagnosed with peripheral artery disease, but there was no increased risk for them requiring any intervention, such as a peripheral vascular intervention, nor were they at increased risk of death from what we found,” said Hirva Vyas, DO, an internal medicine resident at Hackensack University Medical Center in New Jersey, who presented the results at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The study used data on 623,768 marijuana users from the National Inpatient Sample, a nationwide database of inpatient visits covered by all public and commercial payers, then extracted a diagnosis for PAD from all 30 million–plus patient encounters to compare PAD rates between marijuana users and nonusers. Marijuana users were more likely to be White and to have elective rather than emergency admissions (P < .001). The researchers used diagnostic codes to identify marijuana users and PAD patients.

Recreational marijuana is legal in 22 states and the District of Columbia, according to ProCon.org. Since 2019, the last year of the study, 11 states have legalized marijuana for recreational use. “It’s a data point that we studied at one point in time, only from 2016 to 2019,” Dr. Vyas said in an interview.

“As we’ve seen over the past 4-5 years, legalization has skyrocketed and recreational use has become more and more favorable not only among younger folks but older folks,” study coauthor Harsh Jain, MD, a second-year internal medicine resident at Montefiore Medical Center in New York, said in the interview. “It would be really refreshing to see how these data change as we look at endpoints from 2019 to 2023.”

Because of the young age of the study population, Dr. Jain said, these findings may not accurately represent the true cardiovascular risks of marijuana use, especially later in life.

“One of the biggest secondary endpoints that we wanted to study was the development of chronic conditions that lead to multiple rehospitalizations, the most significant one of which would be the development of heart failure,” Dr. Jain said. “However, it was difficult to stratify because, again, many of these patients were very young and so they did not carry the diagnosis for heart failure, so we couldn’t complete that subset analysis.”

The goal is to extend the study period out to 2023, Dr. Jain said. “We know that these are very crude and rudimentary data findings that we presented so far, but we’re hoping that the final paper gives us a chance to flesh out all the details of our study and also gives us a chance to expand going forward,” he said.

The findings are in line with other research into the effects of marijuana and cardiovascular disease, said Carl “Chip” Lavie, MD, medical director for cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute in New Orleans who’s published a number of studies on PAD and substance use, including marijuana.

“It is known that cannabis is associated with more vasoconstriction, has sympathomimetic effects, causes endothelial dysfunction and increased platelet aggregation, and is known to increase the risk of acute myocardial infarction, especially in the hour or so after use,” he said in written comments sent to this news organization.

“It is also well known to be a cause of thromboangiitis obliterans, which is in the PAD family,” he added. “Based on these mechanisms, one would expect an increased PAD and, especially, PAD events. The 3.7-fold increased risk is supportive of this increased PAD.”

One study strength, Dr. Lavie pointed out, is that it’s one of the few studies that found an association between marijuana and PAD, which hasn’t been studied as well as other cardiovascular endpoints. “However,” he said, “the limitation is this is just an inpatient sample, and it is all based on coding – e.g., a patient could have PAD and it may not have been coded.”

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

AURORA, COLO. – Artificial Intelligence has arrived at medical offices, whether or not clinicians feel ready for it.

AI might result in more accurate, efficient, and cost-effective care. But it’s possible it could cause harm. That’s according to Benjamin Collins, MD, at Vanderbilt University Medical Center, Nashville, Tenn., who spoke on the subject at the annual meeting of the Society of General Internal Medicine.

Understanding the nuances of AI is even more important because of the quick development of the algorithms.

“When I submitted this workshop, there was no ChatGPT,” said Dr. Collins, referring to Chat Generative Pre-trained Transformer, a recently released natural language processing model. “A lot has already changed.”
 

Biased data

Biased data are perhaps the biggest pitfall of AI algorithms, Dr. Collins said. If garbage data go in, garbage predictions come out.

If the dataset that trains the algorithm underrepresents a particular gender or ethnic group, for example, the algorithm may not respond accurately to prompts. When an AI tool compounds existing inequalities related to socioeconomic status, ethnicity, or sexual orientation, the algorithm is biased, according to Harvard researchers.

“People often assume that artificial intelligence is free of bias due to the use of scientific processes and its development,” he said. “But whatever flaws exist in data collection and old data can lead to poor representation or underrepresentation in the data used to train the AI tool.”

Racial minorities are underrepresented in studies; therefore, data input into an AI tool might skew results for these patients.

The Framingham Heart Study, for example, which began in 1948, examined heart disease in mainly White participants. The findings from the study resulted in the creation of a sex-specific algorithm that was used to estimate the 10-year cardiovascular risk of a patient. While the cardiovascular risk score was accurate for White persons, it was less accurate for Black patients.

A study published in Science in 2019 revealed bias in an algorithm that used health care costs as a proxy for health needs. Because less money was spent on Black patients who had the same level of need as their White counterparts, the output inaccurately showed that Black patients were healthier and thus did not require extra care.

Developers can also be a source of bias, inasmuch as AI often reflects preexisting human biases, Dr. Collins said.

“Algorithmic bias presents a clear risk of harm that clinicians must play against the benefits of using AI,” Dr. Collins said. “That risk of harm is often disproportionately distributed to marginalized populations.”

As clinicians use AI algorithms to diagnose and detect disease, predict outcomes, and guide treatment, trouble comes when those algorithms perform well for some patients and poorly for others. This gap can exacerbate existing disparities in health care outcomes.

Dr. Collins advised clinicians to push to find out what data were used to train AI algorithms to determine how bias could have influenced the model and whether the developers risk-adjusted for bias. If the training data are not available, clinicians should ask their employers and AI developers to know more about the system.

Clinicians may face the so-called black box phenomenon, which occurs when developers cannot or will not explain what data went into an AI model, Dr. Collins said.

According to Stanford (Calif.) University, AI must be trained on large datasets of images that have been annotated by human experts. Those datasets can cost millions of dollars to create, meaning corporations often fund them and do not always share the data publicly.

Some groups, such as Stanford’s Center for Artificial Intelligence in Medicine and Imaging, are working to acquire annotated datasets so researchers who train AI models can know where the data came from.

Paul Haidet, MD, MPH, an internist at Penn State College of Medicine, Hershey, sees the technology as a tool that requires careful handling.

“It takes a while to learn how to use a stethoscope, and AI is like that,” Dr. Haidet said. “The thing about AI, though, is that it can be just dropped into a system and no one knows how it works.”

Dr. Haidet said he likes knowing how the sausage is made, something AI developers are often reticent to make known.

“If you’re just putting blind faith in a tool, that’s scary,” Dr. Haidet said.
 

Transparency and ‘explainability’

The ability to explain what goes into tools is essential to maintaining trust in the health care system, Dr. Collins said.

“Part of knowing how much trust to place in the system is the transparency of those systems and the ability to audit how well the algorithm is performing,” Dr. Collins said. “The system should also regularly report to users the level of certainty with which it is providing an output rather than providing a simple binary output.”

Dr. Collins recommends that providers develop an understanding of the limits of AI regulations as well, which might including learning how the system was approved and how it is monitored.

“The FDA has oversight over some applications of AI and health care for software as a medical device, but there’s currently no dedicated process to evaluate the systems for the presence of bias,” Dr. Collins said. “The gaps in regulation leave the door open for the use of AI in clinical care that contain significant biases.”

Dr. Haidet likened AI tools to the Global Positioning System: A good GPS system will let users see alternate routes, opt out of toll roads or highways, and will highlight why routes have changed. But users need to understand how to read the map so they can tell when something seems amiss.

Dr. Collins and Dr. Haidet report no relevant financial relationships

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

AURORA, COLO. – Artificial Intelligence has arrived at medical offices, whether or not clinicians feel ready for it.

AI might result in more accurate, efficient, and cost-effective care. But it’s possible it could cause harm. That’s according to Benjamin Collins, MD, at Vanderbilt University Medical Center, Nashville, Tenn., who spoke on the subject at the annual meeting of the Society of General Internal Medicine.

Understanding the nuances of AI is even more important because of the quick development of the algorithms.

“When I submitted this workshop, there was no ChatGPT,” said Dr. Collins, referring to Chat Generative Pre-trained Transformer, a recently released natural language processing model. “A lot has already changed.”
 

Biased data

Biased data are perhaps the biggest pitfall of AI algorithms, Dr. Collins said. If garbage data go in, garbage predictions come out.

If the dataset that trains the algorithm underrepresents a particular gender or ethnic group, for example, the algorithm may not respond accurately to prompts. When an AI tool compounds existing inequalities related to socioeconomic status, ethnicity, or sexual orientation, the algorithm is biased, according to Harvard researchers.

“People often assume that artificial intelligence is free of bias due to the use of scientific processes and its development,” he said. “But whatever flaws exist in data collection and old data can lead to poor representation or underrepresentation in the data used to train the AI tool.”

Racial minorities are underrepresented in studies; therefore, data input into an AI tool might skew results for these patients.

The Framingham Heart Study, for example, which began in 1948, examined heart disease in mainly White participants. The findings from the study resulted in the creation of a sex-specific algorithm that was used to estimate the 10-year cardiovascular risk of a patient. While the cardiovascular risk score was accurate for White persons, it was less accurate for Black patients.

A study published in Science in 2019 revealed bias in an algorithm that used health care costs as a proxy for health needs. Because less money was spent on Black patients who had the same level of need as their White counterparts, the output inaccurately showed that Black patients were healthier and thus did not require extra care.

Developers can also be a source of bias, inasmuch as AI often reflects preexisting human biases, Dr. Collins said.

“Algorithmic bias presents a clear risk of harm that clinicians must play against the benefits of using AI,” Dr. Collins said. “That risk of harm is often disproportionately distributed to marginalized populations.”

As clinicians use AI algorithms to diagnose and detect disease, predict outcomes, and guide treatment, trouble comes when those algorithms perform well for some patients and poorly for others. This gap can exacerbate existing disparities in health care outcomes.

Dr. Collins advised clinicians to push to find out what data were used to train AI algorithms to determine how bias could have influenced the model and whether the developers risk-adjusted for bias. If the training data are not available, clinicians should ask their employers and AI developers to know more about the system.

Clinicians may face the so-called black box phenomenon, which occurs when developers cannot or will not explain what data went into an AI model, Dr. Collins said.

According to Stanford (Calif.) University, AI must be trained on large datasets of images that have been annotated by human experts. Those datasets can cost millions of dollars to create, meaning corporations often fund them and do not always share the data publicly.

Some groups, such as Stanford’s Center for Artificial Intelligence in Medicine and Imaging, are working to acquire annotated datasets so researchers who train AI models can know where the data came from.

Paul Haidet, MD, MPH, an internist at Penn State College of Medicine, Hershey, sees the technology as a tool that requires careful handling.

“It takes a while to learn how to use a stethoscope, and AI is like that,” Dr. Haidet said. “The thing about AI, though, is that it can be just dropped into a system and no one knows how it works.”

Dr. Haidet said he likes knowing how the sausage is made, something AI developers are often reticent to make known.

“If you’re just putting blind faith in a tool, that’s scary,” Dr. Haidet said.
 

Transparency and ‘explainability’

The ability to explain what goes into tools is essential to maintaining trust in the health care system, Dr. Collins said.

“Part of knowing how much trust to place in the system is the transparency of those systems and the ability to audit how well the algorithm is performing,” Dr. Collins said. “The system should also regularly report to users the level of certainty with which it is providing an output rather than providing a simple binary output.”

Dr. Collins recommends that providers develop an understanding of the limits of AI regulations as well, which might including learning how the system was approved and how it is monitored.

“The FDA has oversight over some applications of AI and health care for software as a medical device, but there’s currently no dedicated process to evaluate the systems for the presence of bias,” Dr. Collins said. “The gaps in regulation leave the door open for the use of AI in clinical care that contain significant biases.”

Dr. Haidet likened AI tools to the Global Positioning System: A good GPS system will let users see alternate routes, opt out of toll roads or highways, and will highlight why routes have changed. But users need to understand how to read the map so they can tell when something seems amiss.

Dr. Collins and Dr. Haidet report no relevant financial relationships

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

AURORA, COLO. – Artificial Intelligence has arrived at medical offices, whether or not clinicians feel ready for it.

AI might result in more accurate, efficient, and cost-effective care. But it’s possible it could cause harm. That’s according to Benjamin Collins, MD, at Vanderbilt University Medical Center, Nashville, Tenn., who spoke on the subject at the annual meeting of the Society of General Internal Medicine.

Understanding the nuances of AI is even more important because of the quick development of the algorithms.

“When I submitted this workshop, there was no ChatGPT,” said Dr. Collins, referring to Chat Generative Pre-trained Transformer, a recently released natural language processing model. “A lot has already changed.”
 

Biased data

Biased data are perhaps the biggest pitfall of AI algorithms, Dr. Collins said. If garbage data go in, garbage predictions come out.

If the dataset that trains the algorithm underrepresents a particular gender or ethnic group, for example, the algorithm may not respond accurately to prompts. When an AI tool compounds existing inequalities related to socioeconomic status, ethnicity, or sexual orientation, the algorithm is biased, according to Harvard researchers.

“People often assume that artificial intelligence is free of bias due to the use of scientific processes and its development,” he said. “But whatever flaws exist in data collection and old data can lead to poor representation or underrepresentation in the data used to train the AI tool.”

Racial minorities are underrepresented in studies; therefore, data input into an AI tool might skew results for these patients.

The Framingham Heart Study, for example, which began in 1948, examined heart disease in mainly White participants. The findings from the study resulted in the creation of a sex-specific algorithm that was used to estimate the 10-year cardiovascular risk of a patient. While the cardiovascular risk score was accurate for White persons, it was less accurate for Black patients.

A study published in Science in 2019 revealed bias in an algorithm that used health care costs as a proxy for health needs. Because less money was spent on Black patients who had the same level of need as their White counterparts, the output inaccurately showed that Black patients were healthier and thus did not require extra care.

Developers can also be a source of bias, inasmuch as AI often reflects preexisting human biases, Dr. Collins said.

“Algorithmic bias presents a clear risk of harm that clinicians must play against the benefits of using AI,” Dr. Collins said. “That risk of harm is often disproportionately distributed to marginalized populations.”

As clinicians use AI algorithms to diagnose and detect disease, predict outcomes, and guide treatment, trouble comes when those algorithms perform well for some patients and poorly for others. This gap can exacerbate existing disparities in health care outcomes.

Dr. Collins advised clinicians to push to find out what data were used to train AI algorithms to determine how bias could have influenced the model and whether the developers risk-adjusted for bias. If the training data are not available, clinicians should ask their employers and AI developers to know more about the system.

Clinicians may face the so-called black box phenomenon, which occurs when developers cannot or will not explain what data went into an AI model, Dr. Collins said.

According to Stanford (Calif.) University, AI must be trained on large datasets of images that have been annotated by human experts. Those datasets can cost millions of dollars to create, meaning corporations often fund them and do not always share the data publicly.

Some groups, such as Stanford’s Center for Artificial Intelligence in Medicine and Imaging, are working to acquire annotated datasets so researchers who train AI models can know where the data came from.

Paul Haidet, MD, MPH, an internist at Penn State College of Medicine, Hershey, sees the technology as a tool that requires careful handling.

“It takes a while to learn how to use a stethoscope, and AI is like that,” Dr. Haidet said. “The thing about AI, though, is that it can be just dropped into a system and no one knows how it works.”

Dr. Haidet said he likes knowing how the sausage is made, something AI developers are often reticent to make known.

“If you’re just putting blind faith in a tool, that’s scary,” Dr. Haidet said.
 

Transparency and ‘explainability’

The ability to explain what goes into tools is essential to maintaining trust in the health care system, Dr. Collins said.

“Part of knowing how much trust to place in the system is the transparency of those systems and the ability to audit how well the algorithm is performing,” Dr. Collins said. “The system should also regularly report to users the level of certainty with which it is providing an output rather than providing a simple binary output.”

Dr. Collins recommends that providers develop an understanding of the limits of AI regulations as well, which might including learning how the system was approved and how it is monitored.

“The FDA has oversight over some applications of AI and health care for software as a medical device, but there’s currently no dedicated process to evaluate the systems for the presence of bias,” Dr. Collins said. “The gaps in regulation leave the door open for the use of AI in clinical care that contain significant biases.”

Dr. Haidet likened AI tools to the Global Positioning System: A good GPS system will let users see alternate routes, opt out of toll roads or highways, and will highlight why routes have changed. But users need to understand how to read the map so they can tell when something seems amiss.

Dr. Collins and Dr. Haidet report no relevant financial relationships

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

AURORA, COLO. – How often do you talk with patients about how to lower their out-of-pocket costs for medical care?

For most clinicians, the answer is: not often enough. But having those conversations can improve medication adherence and strengthen the patient-clinician relationship, according to panelists at the annual meeting of the Society of General Internal Medicine.

The inverse association between out-of-pocket expenditures and fidelity to prescriptions is clear. A 2020 study by the IQVIA Institute for Human Data Science, for example, found that rates of prescription abandonment are less than 5% when a given medication carries no out-of-pocket cost for patients. That figure rises to 45% when the cost is more than $125, and to 60% when it exceeds $500. One in five Americans said cost prevented them from adhering to medication regimens, according to a new study in JAMA Network Open.

The researchers surveyed more than 2,000 men and women, 40.4% of whom were aged 75 or older. They found that nearly 90% of respondents said they would not be uncomfortable being asked about drug costs before a visit with a physician. A similar share (89.5%) said they would welcome the use by their physician of a real-time tool to determine the cost of their medication.

But the survey results contained a note of warning for clinicians: A significant number of respondents said they would be “extremely” upset if the cost of their medication exceeded the estimate from the pricing tool. And many also said they would be “moderately” or “extremely” angry if their physician used a pricing tool but failed to share the results with them.

“Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use,” the authors write. “However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.”

While having conversations about cost can be difficult for both clinicians and patients, studies have shown that patients who discuss cost concerns with their doctors feel as if they have stronger relationships as a result.

Clinicians often avoid conversations about out-of-pocket expenses because they don’t know specific price information, they lack solutions to address cost, or they are uncomfortable bringing up the issue.

One member of the audience at the SGIM meeting recalled a patient who worked in a warehouse for a large company. The man, who had type 2 diabetes, had medical insurance, but even with insurance, insulin was going to cost him $150 per month. He struggled to afford the necessary treatment.

“He looked at me and said, ‘What do they want me to do? Do they want me to actually not be able to work for them and not manage my diabetes?’ ”

The clinician said he offered empathy in the moment but felt he could do little else.

Panelists acknowledged that clinicians are crunched on time when seeing patients, but being willing to initiate conversations about cost with patients and to offer resources can help patients get necessary treatment.
 

Start the conversation

Panel member Caroline Sloan, MD, an assistant professor of medicine at Duke University, Durham, N.C., said making patients aware that you know cost can make a big difference.

The American College of Physicians advises clinicians to ask patients whether they are worried about the cost of care and to not assume which patients may have concerns.

The conversation could be started like this: “I’d like to discuss any concerns you might have about the cost of your health care.”

Normalize the concern by making it more general, and reassure your patient that your goal is to get them the best care. Say something like, “I’ve heard from many patients the cost of medications or tests is becoming hard to manage.”

Once a patient’s concerns are clear, you can direct them to resources for assistance in reducing their costs, Dr. Sloan said, such as ClearHealthCosts, FAIR Health, Healthcare Bluebook, New Choice Health, GoodRx, PharmacyChecker, HealthWell Foundation, Patient Advocate Foundation, Good Days, Good Health Will, Mercy Medical Angels, and the American Association of Family Physicians Neighborhood Navigator.

Dr. Sloan said she knows clinicians don’t have time to understand every insurance plan and other issues related to cost. “But at least know to ask about costs,” she said. “Practice, practice, practice. It feels awkward at first, but it gets easier every time.”

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

AURORA, COLO. – How often do you talk with patients about how to lower their out-of-pocket costs for medical care?

For most clinicians, the answer is: not often enough. But having those conversations can improve medication adherence and strengthen the patient-clinician relationship, according to panelists at the annual meeting of the Society of General Internal Medicine.

The inverse association between out-of-pocket expenditures and fidelity to prescriptions is clear. A 2020 study by the IQVIA Institute for Human Data Science, for example, found that rates of prescription abandonment are less than 5% when a given medication carries no out-of-pocket cost for patients. That figure rises to 45% when the cost is more than $125, and to 60% when it exceeds $500. One in five Americans said cost prevented them from adhering to medication regimens, according to a new study in JAMA Network Open.

The researchers surveyed more than 2,000 men and women, 40.4% of whom were aged 75 or older. They found that nearly 90% of respondents said they would not be uncomfortable being asked about drug costs before a visit with a physician. A similar share (89.5%) said they would welcome the use by their physician of a real-time tool to determine the cost of their medication.

But the survey results contained a note of warning for clinicians: A significant number of respondents said they would be “extremely” upset if the cost of their medication exceeded the estimate from the pricing tool. And many also said they would be “moderately” or “extremely” angry if their physician used a pricing tool but failed to share the results with them.

“Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use,” the authors write. “However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.”

While having conversations about cost can be difficult for both clinicians and patients, studies have shown that patients who discuss cost concerns with their doctors feel as if they have stronger relationships as a result.

Clinicians often avoid conversations about out-of-pocket expenses because they don’t know specific price information, they lack solutions to address cost, or they are uncomfortable bringing up the issue.

One member of the audience at the SGIM meeting recalled a patient who worked in a warehouse for a large company. The man, who had type 2 diabetes, had medical insurance, but even with insurance, insulin was going to cost him $150 per month. He struggled to afford the necessary treatment.

“He looked at me and said, ‘What do they want me to do? Do they want me to actually not be able to work for them and not manage my diabetes?’ ”

The clinician said he offered empathy in the moment but felt he could do little else.

Panelists acknowledged that clinicians are crunched on time when seeing patients, but being willing to initiate conversations about cost with patients and to offer resources can help patients get necessary treatment.
 

Start the conversation

Panel member Caroline Sloan, MD, an assistant professor of medicine at Duke University, Durham, N.C., said making patients aware that you know cost can make a big difference.

The American College of Physicians advises clinicians to ask patients whether they are worried about the cost of care and to not assume which patients may have concerns.

The conversation could be started like this: “I’d like to discuss any concerns you might have about the cost of your health care.”

Normalize the concern by making it more general, and reassure your patient that your goal is to get them the best care. Say something like, “I’ve heard from many patients the cost of medications or tests is becoming hard to manage.”

Once a patient’s concerns are clear, you can direct them to resources for assistance in reducing their costs, Dr. Sloan said, such as ClearHealthCosts, FAIR Health, Healthcare Bluebook, New Choice Health, GoodRx, PharmacyChecker, HealthWell Foundation, Patient Advocate Foundation, Good Days, Good Health Will, Mercy Medical Angels, and the American Association of Family Physicians Neighborhood Navigator.

Dr. Sloan said she knows clinicians don’t have time to understand every insurance plan and other issues related to cost. “But at least know to ask about costs,” she said. “Practice, practice, practice. It feels awkward at first, but it gets easier every time.”

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

AURORA, COLO. – How often do you talk with patients about how to lower their out-of-pocket costs for medical care?

For most clinicians, the answer is: not often enough. But having those conversations can improve medication adherence and strengthen the patient-clinician relationship, according to panelists at the annual meeting of the Society of General Internal Medicine.

The inverse association between out-of-pocket expenditures and fidelity to prescriptions is clear. A 2020 study by the IQVIA Institute for Human Data Science, for example, found that rates of prescription abandonment are less than 5% when a given medication carries no out-of-pocket cost for patients. That figure rises to 45% when the cost is more than $125, and to 60% when it exceeds $500. One in five Americans said cost prevented them from adhering to medication regimens, according to a new study in JAMA Network Open.

The researchers surveyed more than 2,000 men and women, 40.4% of whom were aged 75 or older. They found that nearly 90% of respondents said they would not be uncomfortable being asked about drug costs before a visit with a physician. A similar share (89.5%) said they would welcome the use by their physician of a real-time tool to determine the cost of their medication.

But the survey results contained a note of warning for clinicians: A significant number of respondents said they would be “extremely” upset if the cost of their medication exceeded the estimate from the pricing tool. And many also said they would be “moderately” or “extremely” angry if their physician used a pricing tool but failed to share the results with them.

“Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use,” the authors write. “However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.”

While having conversations about cost can be difficult for both clinicians and patients, studies have shown that patients who discuss cost concerns with their doctors feel as if they have stronger relationships as a result.

Clinicians often avoid conversations about out-of-pocket expenses because they don’t know specific price information, they lack solutions to address cost, or they are uncomfortable bringing up the issue.

One member of the audience at the SGIM meeting recalled a patient who worked in a warehouse for a large company. The man, who had type 2 diabetes, had medical insurance, but even with insurance, insulin was going to cost him $150 per month. He struggled to afford the necessary treatment.

“He looked at me and said, ‘What do they want me to do? Do they want me to actually not be able to work for them and not manage my diabetes?’ ”

The clinician said he offered empathy in the moment but felt he could do little else.

Panelists acknowledged that clinicians are crunched on time when seeing patients, but being willing to initiate conversations about cost with patients and to offer resources can help patients get necessary treatment.
 

Start the conversation

Panel member Caroline Sloan, MD, an assistant professor of medicine at Duke University, Durham, N.C., said making patients aware that you know cost can make a big difference.

The American College of Physicians advises clinicians to ask patients whether they are worried about the cost of care and to not assume which patients may have concerns.

The conversation could be started like this: “I’d like to discuss any concerns you might have about the cost of your health care.”

Normalize the concern by making it more general, and reassure your patient that your goal is to get them the best care. Say something like, “I’ve heard from many patients the cost of medications or tests is becoming hard to manage.”

Once a patient’s concerns are clear, you can direct them to resources for assistance in reducing their costs, Dr. Sloan said, such as ClearHealthCosts, FAIR Health, Healthcare Bluebook, New Choice Health, GoodRx, PharmacyChecker, HealthWell Foundation, Patient Advocate Foundation, Good Days, Good Health Will, Mercy Medical Angels, and the American Association of Family Physicians Neighborhood Navigator.

Dr. Sloan said she knows clinicians don’t have time to understand every insurance plan and other issues related to cost. “But at least know to ask about costs,” she said. “Practice, practice, practice. It feels awkward at first, but it gets easier every time.”

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

Using age-specific thresholds for troponin measurement would more accurately diagnose myocardial injury when assessing patients for suspected myocardial infarction, a study suggests.
 

The study shows that the 99th percentile for the upper reference limit (used to define myocardial injury) for high-sensitivity (hs)–troponin T in the new analysis matched those reported by manufacturers. However, the same threshold for hs–troponin I was lower than was manufacturer-reported levels when considering the whole population.

And for both hs–troponin T and hs–troponin I, there were significant differences in 99th percentile levels by age.

“Our data suggest that some cases of myocardial injury may be missed in the whole population by using current non–age specific thresholds of troponin I,” lead author, John McEvoy, MB, University of Galway (Ireland), said in an interview. “If the non–age specific threshold was lowered to that in our cohort, then we would pick up more people with myocardial injury.”

“However,” Dr. McEvoy added, “if age-specific thresholds were deployed, then our data suggest that thresholds used to diagnose myocardial injury would need to be higher in older adults, somewhat lower in middle-aged individuals and much lower in younger people.”

The study was published online in the Journal of the American College of Cardiology.  

The authors explain that the 99th percentile upper–reference limit threshold is the common benchmark of abnormality for all troponin assays. Five high-sensitivity cardiac troponin assays have been cleared by the Food and Drug Administration for clinical use and allow for earlier diagnosis of MI.

However, there has been variability in the approach used to define the 99th percentile upper reference limits for these assays, with definitions of healthy reference populations differing and the various assays available are not standardized or harmonized. So troponin concentrations at 99th percentiles do not align across assays, and the generalizability of manufacturer-reported reference upper reference limits for hs-troponin assays to the U.S. adult population is unknown.

They note that though sex-specific 99th percentile upper reference limits for hs-troponin have been recommended since 2018, age-specific thresholds are not yet endorsed, and whether thresholds differ by race or ethnicity is also controversial.

They aimed to investigate these issues using stored serum samples from adults aged 18 or older who participated in the 1999-2004 National Health and Nutrition Examination Survey (NHANES).

Dr. McEvoy described the NHANES database as “the gold standard cohort for representation of the U.S. adult population,” noting that other studies conducted by the manufacturers of the troponin tests have often used convenience samples from patients attending hospital clinics and blood donors, which he said were not representative of the whole population.

For the study, the researchers estimated that the 99th percentile upper reference limit for four hs-troponin assays (one troponin T and three troponin I) in a strictly defined healthy reference subgroup of 2,746 individuals from the NHANES cohort.

Results showed that the NHANES 99th percentile upper reference limit for hs–troponin T (19 ng/L) matched the manufacturer-reported level (19 ng/L). But, the NHANES upper reference levels for three troponin I assays were lower than were levels stated by the manufacturers.

The NHANES levels were 13 ng/L for the Abbott hs–troponin I assay (manufacturer: 28 ng/L); 5 ng/L for the Ortho hs–troponin I assay (manufacturer: 11 ng/L); and 37 ng/L for the Siemens hs–troponin I assay (manufacturer: 46.5 ng/L).

Furthermore, the 99th percentile upper reference limits for all four hs-troponin assays were statistically significantly lower in healthy adults younger than 40 years, compared with healthy adults older than 60 years.

There were also significant differences in upper reference limits by sex, but none by race/ethnicity.

Dr. McEvoy explained that NHANES is a very well phenotyped database with information on individuals’ health, body mass index, and other biomarkers. “This allows us to define a completely healthy subgroup of people, which could explain why the 99th percentile threshold for hs–troponin I was lower than previously reported from other cohorts,” he added.

Though there may be concern that such a healthy subgroup would mean the sample is enriched with younger people, whereas the typical person having their troponin measured would be older, Dr. McEvoy pointed out that there were more than 400 people older than 60 years in the healthy group. “This is probably the biggest cohort of super healthy older U.S. adults ever sampled in this regard,” he commented.

Dr. McEvoy said that the overall results from the study suggested that different thresholds might need to be considered for troponin I. “This could lead to threshold levels used to diagnose myocardial injury being cut in the population as a whole.”

But, he said a more important message was the need for age-specific thresholds.

“We found that troponin levels track with age. Even in individuals who age in a very healthy way, their troponin levels are greater than in younger people. This is the first time this has been shown with such clear statistical significance,” Dr. McEvoy said. “We think this data provides a compelling case for the use of age-specific cut-offs.”

He explained that, if age-specific thresholds were used to diagnose myocardial injury, the cut point from the current data would be higher than it would be from current manufacturers’ recommendations in those older than 60 years, so fewer people in this age group would be labeled as having myocardial injury.

“Our results suggest that, at present, we are seeing more false positives in older people leading to more unnecessary tests.” Using age-specific cut off points will reduce the number of false positives in older people. Dr. McEvoy noted a similar change in the way D-Dimer blood tests have been used to diagnose pulmonary embolism in recent years.

Using age-specific cut-offs for hs-troponin would also reduce the number of false negatives in younger people, Dr. McEvoy added.
 

Further studies needed?

In an accompanying editorial, Cian McCarthy, MB, Austin Vyas, and James Januzzi, MD, of Massachusetts General Hospital, Boston, note that though there are substantial shortcomings to using the 99th percentile upper reference limit of troponins for the diagnosis of cardiac injury, they believe this measurement should persist as a central component of the MI diagnostic criteria, with the caveat that this is only one component of the definition of MI and does not alone define it.

“Cardiac troponin measurement is one of the most commonly utilized blood tests in hospital-based settings, and yet important questions remain about what exactly is a normal value for this test,” the editorialists comment.

They say this new study emphasizes the importance of age and sex in interpretation of troponin levels.

“Although the use of such cut-offs may further complicate MI diagnostic criteria, this is superseded by the benefits of improved diagnostic accuracy in younger and female patients (a critical health equity step) while reducing MI overdiagnosis in the elderly, with the resultant harms that might follow, adverse psychosocial patient impact, and unnecessary health care expenditure from cascade testing,” they write.

They conclude that further large studies derived from healthy cohorts should be conducted to answer this question in a definitive fashion.

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

Using age-specific thresholds for troponin measurement would more accurately diagnose myocardial injury when assessing patients for suspected myocardial infarction, a study suggests.
 

The study shows that the 99th percentile for the upper reference limit (used to define myocardial injury) for high-sensitivity (hs)–troponin T in the new analysis matched those reported by manufacturers. However, the same threshold for hs–troponin I was lower than was manufacturer-reported levels when considering the whole population.

And for both hs–troponin T and hs–troponin I, there were significant differences in 99th percentile levels by age.

“Our data suggest that some cases of myocardial injury may be missed in the whole population by using current non–age specific thresholds of troponin I,” lead author, John McEvoy, MB, University of Galway (Ireland), said in an interview. “If the non–age specific threshold was lowered to that in our cohort, then we would pick up more people with myocardial injury.”

“However,” Dr. McEvoy added, “if age-specific thresholds were deployed, then our data suggest that thresholds used to diagnose myocardial injury would need to be higher in older adults, somewhat lower in middle-aged individuals and much lower in younger people.”

The study was published online in the Journal of the American College of Cardiology.  

The authors explain that the 99th percentile upper–reference limit threshold is the common benchmark of abnormality for all troponin assays. Five high-sensitivity cardiac troponin assays have been cleared by the Food and Drug Administration for clinical use and allow for earlier diagnosis of MI.

However, there has been variability in the approach used to define the 99th percentile upper reference limits for these assays, with definitions of healthy reference populations differing and the various assays available are not standardized or harmonized. So troponin concentrations at 99th percentiles do not align across assays, and the generalizability of manufacturer-reported reference upper reference limits for hs-troponin assays to the U.S. adult population is unknown.

They note that though sex-specific 99th percentile upper reference limits for hs-troponin have been recommended since 2018, age-specific thresholds are not yet endorsed, and whether thresholds differ by race or ethnicity is also controversial.

They aimed to investigate these issues using stored serum samples from adults aged 18 or older who participated in the 1999-2004 National Health and Nutrition Examination Survey (NHANES).

Dr. McEvoy described the NHANES database as “the gold standard cohort for representation of the U.S. adult population,” noting that other studies conducted by the manufacturers of the troponin tests have often used convenience samples from patients attending hospital clinics and blood donors, which he said were not representative of the whole population.

For the study, the researchers estimated that the 99th percentile upper reference limit for four hs-troponin assays (one troponin T and three troponin I) in a strictly defined healthy reference subgroup of 2,746 individuals from the NHANES cohort.

Results showed that the NHANES 99th percentile upper reference limit for hs–troponin T (19 ng/L) matched the manufacturer-reported level (19 ng/L). But, the NHANES upper reference levels for three troponin I assays were lower than were levels stated by the manufacturers.

The NHANES levels were 13 ng/L for the Abbott hs–troponin I assay (manufacturer: 28 ng/L); 5 ng/L for the Ortho hs–troponin I assay (manufacturer: 11 ng/L); and 37 ng/L for the Siemens hs–troponin I assay (manufacturer: 46.5 ng/L).

Furthermore, the 99th percentile upper reference limits for all four hs-troponin assays were statistically significantly lower in healthy adults younger than 40 years, compared with healthy adults older than 60 years.

There were also significant differences in upper reference limits by sex, but none by race/ethnicity.

Dr. McEvoy explained that NHANES is a very well phenotyped database with information on individuals’ health, body mass index, and other biomarkers. “This allows us to define a completely healthy subgroup of people, which could explain why the 99th percentile threshold for hs–troponin I was lower than previously reported from other cohorts,” he added.

Though there may be concern that such a healthy subgroup would mean the sample is enriched with younger people, whereas the typical person having their troponin measured would be older, Dr. McEvoy pointed out that there were more than 400 people older than 60 years in the healthy group. “This is probably the biggest cohort of super healthy older U.S. adults ever sampled in this regard,” he commented.

Dr. McEvoy said that the overall results from the study suggested that different thresholds might need to be considered for troponin I. “This could lead to threshold levels used to diagnose myocardial injury being cut in the population as a whole.”

But, he said a more important message was the need for age-specific thresholds.

“We found that troponin levels track with age. Even in individuals who age in a very healthy way, their troponin levels are greater than in younger people. This is the first time this has been shown with such clear statistical significance,” Dr. McEvoy said. “We think this data provides a compelling case for the use of age-specific cut-offs.”

He explained that, if age-specific thresholds were used to diagnose myocardial injury, the cut point from the current data would be higher than it would be from current manufacturers’ recommendations in those older than 60 years, so fewer people in this age group would be labeled as having myocardial injury.

“Our results suggest that, at present, we are seeing more false positives in older people leading to more unnecessary tests.” Using age-specific cut off points will reduce the number of false positives in older people. Dr. McEvoy noted a similar change in the way D-Dimer blood tests have been used to diagnose pulmonary embolism in recent years.

Using age-specific cut-offs for hs-troponin would also reduce the number of false negatives in younger people, Dr. McEvoy added.
 

Further studies needed?

In an accompanying editorial, Cian McCarthy, MB, Austin Vyas, and James Januzzi, MD, of Massachusetts General Hospital, Boston, note that though there are substantial shortcomings to using the 99th percentile upper reference limit of troponins for the diagnosis of cardiac injury, they believe this measurement should persist as a central component of the MI diagnostic criteria, with the caveat that this is only one component of the definition of MI and does not alone define it.

“Cardiac troponin measurement is one of the most commonly utilized blood tests in hospital-based settings, and yet important questions remain about what exactly is a normal value for this test,” the editorialists comment.

They say this new study emphasizes the importance of age and sex in interpretation of troponin levels.

“Although the use of such cut-offs may further complicate MI diagnostic criteria, this is superseded by the benefits of improved diagnostic accuracy in younger and female patients (a critical health equity step) while reducing MI overdiagnosis in the elderly, with the resultant harms that might follow, adverse psychosocial patient impact, and unnecessary health care expenditure from cascade testing,” they write.

They conclude that further large studies derived from healthy cohorts should be conducted to answer this question in a definitive fashion.

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

Using age-specific thresholds for troponin measurement would more accurately diagnose myocardial injury when assessing patients for suspected myocardial infarction, a study suggests.
 

The study shows that the 99th percentile for the upper reference limit (used to define myocardial injury) for high-sensitivity (hs)–troponin T in the new analysis matched those reported by manufacturers. However, the same threshold for hs–troponin I was lower than was manufacturer-reported levels when considering the whole population.

And for both hs–troponin T and hs–troponin I, there were significant differences in 99th percentile levels by age.

“Our data suggest that some cases of myocardial injury may be missed in the whole population by using current non–age specific thresholds of troponin I,” lead author, John McEvoy, MB, University of Galway (Ireland), said in an interview. “If the non–age specific threshold was lowered to that in our cohort, then we would pick up more people with myocardial injury.”

“However,” Dr. McEvoy added, “if age-specific thresholds were deployed, then our data suggest that thresholds used to diagnose myocardial injury would need to be higher in older adults, somewhat lower in middle-aged individuals and much lower in younger people.”

The study was published online in the Journal of the American College of Cardiology.  

The authors explain that the 99th percentile upper–reference limit threshold is the common benchmark of abnormality for all troponin assays. Five high-sensitivity cardiac troponin assays have been cleared by the Food and Drug Administration for clinical use and allow for earlier diagnosis of MI.

However, there has been variability in the approach used to define the 99th percentile upper reference limits for these assays, with definitions of healthy reference populations differing and the various assays available are not standardized or harmonized. So troponin concentrations at 99th percentiles do not align across assays, and the generalizability of manufacturer-reported reference upper reference limits for hs-troponin assays to the U.S. adult population is unknown.

They note that though sex-specific 99th percentile upper reference limits for hs-troponin have been recommended since 2018, age-specific thresholds are not yet endorsed, and whether thresholds differ by race or ethnicity is also controversial.

They aimed to investigate these issues using stored serum samples from adults aged 18 or older who participated in the 1999-2004 National Health and Nutrition Examination Survey (NHANES).

Dr. McEvoy described the NHANES database as “the gold standard cohort for representation of the U.S. adult population,” noting that other studies conducted by the manufacturers of the troponin tests have often used convenience samples from patients attending hospital clinics and blood donors, which he said were not representative of the whole population.

For the study, the researchers estimated that the 99th percentile upper reference limit for four hs-troponin assays (one troponin T and three troponin I) in a strictly defined healthy reference subgroup of 2,746 individuals from the NHANES cohort.

Results showed that the NHANES 99th percentile upper reference limit for hs–troponin T (19 ng/L) matched the manufacturer-reported level (19 ng/L). But, the NHANES upper reference levels for three troponin I assays were lower than were levels stated by the manufacturers.

The NHANES levels were 13 ng/L for the Abbott hs–troponin I assay (manufacturer: 28 ng/L); 5 ng/L for the Ortho hs–troponin I assay (manufacturer: 11 ng/L); and 37 ng/L for the Siemens hs–troponin I assay (manufacturer: 46.5 ng/L).

Furthermore, the 99th percentile upper reference limits for all four hs-troponin assays were statistically significantly lower in healthy adults younger than 40 years, compared with healthy adults older than 60 years.

There were also significant differences in upper reference limits by sex, but none by race/ethnicity.

Dr. McEvoy explained that NHANES is a very well phenotyped database with information on individuals’ health, body mass index, and other biomarkers. “This allows us to define a completely healthy subgroup of people, which could explain why the 99th percentile threshold for hs–troponin I was lower than previously reported from other cohorts,” he added.

Though there may be concern that such a healthy subgroup would mean the sample is enriched with younger people, whereas the typical person having their troponin measured would be older, Dr. McEvoy pointed out that there were more than 400 people older than 60 years in the healthy group. “This is probably the biggest cohort of super healthy older U.S. adults ever sampled in this regard,” he commented.

Dr. McEvoy said that the overall results from the study suggested that different thresholds might need to be considered for troponin I. “This could lead to threshold levels used to diagnose myocardial injury being cut in the population as a whole.”

But, he said a more important message was the need for age-specific thresholds.

“We found that troponin levels track with age. Even in individuals who age in a very healthy way, their troponin levels are greater than in younger people. This is the first time this has been shown with such clear statistical significance,” Dr. McEvoy said. “We think this data provides a compelling case for the use of age-specific cut-offs.”

He explained that, if age-specific thresholds were used to diagnose myocardial injury, the cut point from the current data would be higher than it would be from current manufacturers’ recommendations in those older than 60 years, so fewer people in this age group would be labeled as having myocardial injury.

“Our results suggest that, at present, we are seeing more false positives in older people leading to more unnecessary tests.” Using age-specific cut off points will reduce the number of false positives in older people. Dr. McEvoy noted a similar change in the way D-Dimer blood tests have been used to diagnose pulmonary embolism in recent years.

Using age-specific cut-offs for hs-troponin would also reduce the number of false negatives in younger people, Dr. McEvoy added.
 

Further studies needed?

In an accompanying editorial, Cian McCarthy, MB, Austin Vyas, and James Januzzi, MD, of Massachusetts General Hospital, Boston, note that though there are substantial shortcomings to using the 99th percentile upper reference limit of troponins for the diagnosis of cardiac injury, they believe this measurement should persist as a central component of the MI diagnostic criteria, with the caveat that this is only one component of the definition of MI and does not alone define it.

“Cardiac troponin measurement is one of the most commonly utilized blood tests in hospital-based settings, and yet important questions remain about what exactly is a normal value for this test,” the editorialists comment.

They say this new study emphasizes the importance of age and sex in interpretation of troponin levels.

“Although the use of such cut-offs may further complicate MI diagnostic criteria, this is superseded by the benefits of improved diagnostic accuracy in younger and female patients (a critical health equity step) while reducing MI overdiagnosis in the elderly, with the resultant harms that might follow, adverse psychosocial patient impact, and unnecessary health care expenditure from cascade testing,” they write.

They conclude that further large studies derived from healthy cohorts should be conducted to answer this question in a definitive fashion.

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

DUBLIN – Nearly half (45%) of adolescents assigned to semaglutide (Wegovy), a once-weekly glucagon-like peptide-1 (GLP-1) agonist, managed to lose enough weight to drop below the clinical threshold for obesity, according to a secondary analysis of the STEP TEENS (Semaglutide Treatment Effect in People With Obesity) trial.
 

By comparison, only 12.1% of adolescents with obesity taking placebo in the trial dropped below the obesity threshold.

The study also found that 74% of participants shifted down by at least one body mass index (BMI) category after receiving the GLP-1 agonist, compared with 19% of those taking placebo.

Semaglutide shifts BMI category

In this new secondary analysis of STEP TEENS, the authors examined the effect of subcutaneous semaglutide 2.4 mg on moving adolescents from one BMI category to another, including dropping below the obesity threshold into the overweight or normal weight categories.

The study also looked at the effect of semaglutide on glucose metabolism and cardiovascular risk factors, as well as safety and tolerability. However, this particular analysis only examined adolescents with obesity (only one person had overweight, and so they were excluded), who were divided into three further subclasses: obesity class I (BMI ≥ 95th to < 20% above the 95th percentile); obesity class II (BMI ≥ 20% to < 40% above 95th percentile); and obesity class III (BMI ≥ 40% above the 95th percentile).

After a 12-week run-in period of lifestyle intervention only, a total of 200 adolescents (12-18 years) with obesity (in the top 5% of BMI) were randomized (2:1) to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, after a 16-week titration period. All participants continued to receive counseling about healthy nutrition and were set a goal of 60 minutes per day of moderate- to high-intensity physical activity.

Dr. Kelly and colleagues determined levels of improvement in BMI category and attainment of normal weight, or overweight, BMI category by week 68.

At baseline, the percentage of participants in obesity class I, II, or III, in those taking placebo was 39.7%, 41.4%, and 19.0%, or taking semaglutide was 31.4%, 31.4%, and 37.3%, respectively.

“After 68 weeks, not a lot happened [in placebo participants]; however, 12.1% of placebo participants did drop below the obesity threshold into overweight or normal-weight categories,” reported Dr. Kelly.

Referring to participants taking semaglutide, he added that “a total of 45% of patients on semaglutide dropped below the clinical BMI cut point for obesity, such that 19.5% dropped into the overweight category and 25.4% reduced their BMI into the normal-weight category.”

Turning to obesity class, Dr. Kelly reported that of those initially with obesity class III taking placebo, 91% remained in that class and 9.1% dropped to obesity class II at week 68. For those adolescents with obesity class III taking semaglutide, 36.4% dropped to obesity class II, 18.2% dropped to obesity class I, 11% dropped below the obesity threshold, and 34.1% remained in obesity class III, he added.

For obesity class II specifically, 71% of placebo participants stayed in that category, while 12% moved up a category. “On semaglutide, over 50% (51.2%) reduced their BMI below the obesity cut point,” noted Dr. Kelly.

In obesity class I, 26% of patients taking placebo reduced their BMI below the obesity cut point. “On semaglutide, nearly 80% reduced their BMI below the obesity threshold, with 57% dropping their BMI into the normal category,” he said.

“When we looked at baseline factors that might predict the response to semaglutide or placebo, we did not find any factors that were ... significant due to small sample sizes,” he said. However, he pointed out that “females tended to respond better to semaglutide, likewise younger adolescents, and middle body weights tended to respond better to the drug, and there was a similar pattern with obesity classes.”

Commenting on the study, Jesse Bittman, MD, University of British Columbia, Vancouver, said: “Good to see more data on different populations that some semaglutide is used in and the variability in response to it. The focus on BMI was interesting because in obesity medicine we spend a lot of time telling our patients not to focus on BMIs and ‘normals’ because there are more important tools, and we see that when these become the focus of research outcomes they can become problematic.”

Asked whether rapid weight loss in adolescents might be problematic in some respects, Dr. Bittman pointed out that “one concern with these medications is whether people are going to have loss of muscle mass or malnutrition, or whether they develop eating disorders and other disturbed eating behaviors.”

Dr. Kelly has reported engaging in unpaid consulting and educational activities for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Vivus, and receiving donated drug/placebo from Novo Nordisk and Vivus for National Institutes of Health–funded clinical trials. Dr. O’Malley has declared having received grants in the past 3 years from the Health Research Board, Department of Health, Ireland, European Association for the Study of Obesity (via a Novo Nordisk educational grant), Healthy Ireland fund, and the Royal College of Surgeons in Ireland Strategic Academic Recruitment (StAR) Programme. Dr. Bittman has reported receiving funding from Novo Nordisk, Bayer, and Bausch Health.

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

DUBLIN – Nearly half (45%) of adolescents assigned to semaglutide (Wegovy), a once-weekly glucagon-like peptide-1 (GLP-1) agonist, managed to lose enough weight to drop below the clinical threshold for obesity, according to a secondary analysis of the STEP TEENS (Semaglutide Treatment Effect in People With Obesity) trial.
 

By comparison, only 12.1% of adolescents with obesity taking placebo in the trial dropped below the obesity threshold.

The study also found that 74% of participants shifted down by at least one body mass index (BMI) category after receiving the GLP-1 agonist, compared with 19% of those taking placebo.

Semaglutide shifts BMI category

In this new secondary analysis of STEP TEENS, the authors examined the effect of subcutaneous semaglutide 2.4 mg on moving adolescents from one BMI category to another, including dropping below the obesity threshold into the overweight or normal weight categories.

The study also looked at the effect of semaglutide on glucose metabolism and cardiovascular risk factors, as well as safety and tolerability. However, this particular analysis only examined adolescents with obesity (only one person had overweight, and so they were excluded), who were divided into three further subclasses: obesity class I (BMI ≥ 95th to < 20% above the 95th percentile); obesity class II (BMI ≥ 20% to < 40% above 95th percentile); and obesity class III (BMI ≥ 40% above the 95th percentile).

After a 12-week run-in period of lifestyle intervention only, a total of 200 adolescents (12-18 years) with obesity (in the top 5% of BMI) were randomized (2:1) to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, after a 16-week titration period. All participants continued to receive counseling about healthy nutrition and were set a goal of 60 minutes per day of moderate- to high-intensity physical activity.

Dr. Kelly and colleagues determined levels of improvement in BMI category and attainment of normal weight, or overweight, BMI category by week 68.

At baseline, the percentage of participants in obesity class I, II, or III, in those taking placebo was 39.7%, 41.4%, and 19.0%, or taking semaglutide was 31.4%, 31.4%, and 37.3%, respectively.

“After 68 weeks, not a lot happened [in placebo participants]; however, 12.1% of placebo participants did drop below the obesity threshold into overweight or normal-weight categories,” reported Dr. Kelly.

Referring to participants taking semaglutide, he added that “a total of 45% of patients on semaglutide dropped below the clinical BMI cut point for obesity, such that 19.5% dropped into the overweight category and 25.4% reduced their BMI into the normal-weight category.”

Turning to obesity class, Dr. Kelly reported that of those initially with obesity class III taking placebo, 91% remained in that class and 9.1% dropped to obesity class II at week 68. For those adolescents with obesity class III taking semaglutide, 36.4% dropped to obesity class II, 18.2% dropped to obesity class I, 11% dropped below the obesity threshold, and 34.1% remained in obesity class III, he added.

For obesity class II specifically, 71% of placebo participants stayed in that category, while 12% moved up a category. “On semaglutide, over 50% (51.2%) reduced their BMI below the obesity cut point,” noted Dr. Kelly.

In obesity class I, 26% of patients taking placebo reduced their BMI below the obesity cut point. “On semaglutide, nearly 80% reduced their BMI below the obesity threshold, with 57% dropping their BMI into the normal category,” he said.

“When we looked at baseline factors that might predict the response to semaglutide or placebo, we did not find any factors that were ... significant due to small sample sizes,” he said. However, he pointed out that “females tended to respond better to semaglutide, likewise younger adolescents, and middle body weights tended to respond better to the drug, and there was a similar pattern with obesity classes.”

Commenting on the study, Jesse Bittman, MD, University of British Columbia, Vancouver, said: “Good to see more data on different populations that some semaglutide is used in and the variability in response to it. The focus on BMI was interesting because in obesity medicine we spend a lot of time telling our patients not to focus on BMIs and ‘normals’ because there are more important tools, and we see that when these become the focus of research outcomes they can become problematic.”

Asked whether rapid weight loss in adolescents might be problematic in some respects, Dr. Bittman pointed out that “one concern with these medications is whether people are going to have loss of muscle mass or malnutrition, or whether they develop eating disorders and other disturbed eating behaviors.”

Dr. Kelly has reported engaging in unpaid consulting and educational activities for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Vivus, and receiving donated drug/placebo from Novo Nordisk and Vivus for National Institutes of Health–funded clinical trials. Dr. O’Malley has declared having received grants in the past 3 years from the Health Research Board, Department of Health, Ireland, European Association for the Study of Obesity (via a Novo Nordisk educational grant), Healthy Ireland fund, and the Royal College of Surgeons in Ireland Strategic Academic Recruitment (StAR) Programme. Dr. Bittman has reported receiving funding from Novo Nordisk, Bayer, and Bausch Health.

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

DUBLIN – Nearly half (45%) of adolescents assigned to semaglutide (Wegovy), a once-weekly glucagon-like peptide-1 (GLP-1) agonist, managed to lose enough weight to drop below the clinical threshold for obesity, according to a secondary analysis of the STEP TEENS (Semaglutide Treatment Effect in People With Obesity) trial.
 

By comparison, only 12.1% of adolescents with obesity taking placebo in the trial dropped below the obesity threshold.

The study also found that 74% of participants shifted down by at least one body mass index (BMI) category after receiving the GLP-1 agonist, compared with 19% of those taking placebo.

Semaglutide shifts BMI category

In this new secondary analysis of STEP TEENS, the authors examined the effect of subcutaneous semaglutide 2.4 mg on moving adolescents from one BMI category to another, including dropping below the obesity threshold into the overweight or normal weight categories.

The study also looked at the effect of semaglutide on glucose metabolism and cardiovascular risk factors, as well as safety and tolerability. However, this particular analysis only examined adolescents with obesity (only one person had overweight, and so they were excluded), who were divided into three further subclasses: obesity class I (BMI ≥ 95th to < 20% above the 95th percentile); obesity class II (BMI ≥ 20% to < 40% above 95th percentile); and obesity class III (BMI ≥ 40% above the 95th percentile).

After a 12-week run-in period of lifestyle intervention only, a total of 200 adolescents (12-18 years) with obesity (in the top 5% of BMI) were randomized (2:1) to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, after a 16-week titration period. All participants continued to receive counseling about healthy nutrition and were set a goal of 60 minutes per day of moderate- to high-intensity physical activity.

Dr. Kelly and colleagues determined levels of improvement in BMI category and attainment of normal weight, or overweight, BMI category by week 68.

At baseline, the percentage of participants in obesity class I, II, or III, in those taking placebo was 39.7%, 41.4%, and 19.0%, or taking semaglutide was 31.4%, 31.4%, and 37.3%, respectively.

“After 68 weeks, not a lot happened [in placebo participants]; however, 12.1% of placebo participants did drop below the obesity threshold into overweight or normal-weight categories,” reported Dr. Kelly.

Referring to participants taking semaglutide, he added that “a total of 45% of patients on semaglutide dropped below the clinical BMI cut point for obesity, such that 19.5% dropped into the overweight category and 25.4% reduced their BMI into the normal-weight category.”

Turning to obesity class, Dr. Kelly reported that of those initially with obesity class III taking placebo, 91% remained in that class and 9.1% dropped to obesity class II at week 68. For those adolescents with obesity class III taking semaglutide, 36.4% dropped to obesity class II, 18.2% dropped to obesity class I, 11% dropped below the obesity threshold, and 34.1% remained in obesity class III, he added.

For obesity class II specifically, 71% of placebo participants stayed in that category, while 12% moved up a category. “On semaglutide, over 50% (51.2%) reduced their BMI below the obesity cut point,” noted Dr. Kelly.

In obesity class I, 26% of patients taking placebo reduced their BMI below the obesity cut point. “On semaglutide, nearly 80% reduced their BMI below the obesity threshold, with 57% dropping their BMI into the normal category,” he said.

“When we looked at baseline factors that might predict the response to semaglutide or placebo, we did not find any factors that were ... significant due to small sample sizes,” he said. However, he pointed out that “females tended to respond better to semaglutide, likewise younger adolescents, and middle body weights tended to respond better to the drug, and there was a similar pattern with obesity classes.”

Commenting on the study, Jesse Bittman, MD, University of British Columbia, Vancouver, said: “Good to see more data on different populations that some semaglutide is used in and the variability in response to it. The focus on BMI was interesting because in obesity medicine we spend a lot of time telling our patients not to focus on BMIs and ‘normals’ because there are more important tools, and we see that when these become the focus of research outcomes they can become problematic.”

Asked whether rapid weight loss in adolescents might be problematic in some respects, Dr. Bittman pointed out that “one concern with these medications is whether people are going to have loss of muscle mass or malnutrition, or whether they develop eating disorders and other disturbed eating behaviors.”

Dr. Kelly has reported engaging in unpaid consulting and educational activities for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Vivus, and receiving donated drug/placebo from Novo Nordisk and Vivus for National Institutes of Health–funded clinical trials. Dr. O’Malley has declared having received grants in the past 3 years from the Health Research Board, Department of Health, Ireland, European Association for the Study of Obesity (via a Novo Nordisk educational grant), Healthy Ireland fund, and the Royal College of Surgeons in Ireland Strategic Academic Recruitment (StAR) Programme. Dr. Bittman has reported receiving funding from Novo Nordisk, Bayer, and Bausch Health.

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