Ted Bosworth

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

For patients undergoing transcatheter aortic valve replacement (TAVR), the intentional laceration technique of diseased valve leaflets called BASILICA is effective and reasonably safe for preventing coronary artery obstruction, according to a late-breaking study presented at CRT 2021 sponsored by MedStar Heart & Vascular Institute.

In a series of 214 patients entered into a registry over a recent 30-month period, leaflets posing risk were effectively traversed with the technique in 95% of cases, and complication rates were reasonably low with 30-day stroke and death rate of 3.4%, reported Jaffar M. Khan, BMBCH, PhD, cardiovascular branch of the National Heart, Lung, and Blood Institute.

The rate of complications is acceptable given the large potential risk, according to Dr. Khan. If coronary obstruction occurs, reported mortality rates have been as high as 50%. The 1-year survival rate in the registry following BASILICA was 84%.
 

Results should ‘push people toward BASILICA’

The acronym BASILICA stands for bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction. In the procedure, performed immediately before TAVR, guidewires are introduced to first traverse and then lacerate aortic leaflets threatening obstruction of a coronary artery.

In cases where diseased valve leaflets pose a risk of coronary obstruction, most interventionalists “are comfortable with surgery when patients are at low or intermediate risk, but the choices for high-risk patients are a snorkel stent or BASILICA. Given the limits of snorkel stenting, these data should be reassuring and push people toward BASILICA,” Dr. Khan said.

The 214 patients were entered into the registry from June 2015 to December 2020. The mean age was 74.9 years. Of valves treated, 73% were failed bioprosthetic devices. The remaining were native aortic valves. Solo BASILICA was performed in most patients, but 21.5% underwent a doppio procedure, meaning the laceration of two leaflets.

Despite BASILICA, 10 patients (4.7%) had some degree of coronary obstruction, including 5 with partial obstruction of the main coronary artery and 1 with partial obstruction of the right coronary artery. All of these partial obstructions were successfully treated with orthotopic stents.

An obstruction of the right coronary artery was successfully treated with balloon angioplasty. Another patient with significant left main coronary artery obstruction required cardiopulmonary bypass but was successfully treated with snorkel stenting. Of two patients with complete obstruction of the left main coronary artery caused by the skirt of the TAVR device, one died in hospital despite several maneuvers to restore perfusion.

Procedural complications included a mitral chord laceration, which subsequently led to valve replacement, and three guidewire transversals into surrounding tissue that did not result in serious sequelae. Hypotension requiring pressors occurred in 8.5%.

There was a “slight trend” for worse outcomes in those undergoing doppio rather than solo BASILICA, but the difference did not reach statistical significance. Cerebral embolic protection was offered to a minority of patients in this series. The trend for a lower risk of stroke in this group did not reach significance, Dr. Khan reported.
 

Best for high-volume centers, for now

Although these data support the conclusion that BASILICA “is feasible in a real-world setting,” Dr. Khan acknowledged that BASILICA might not be appropriate at low-volume centers. Dr. Khan cited data that indicates obstruction of a coronary artery by a diseased leaflet occurs in less than 1% of TAVR cases.

“Not every site doing a handful of TAVRs is going to want to tackle these cases, but those working in a high-volume center will from time to time encounter patients with coronary obstruction or who are at increased risk,” Dr. Khan said.

In North America, there has been a proctoring program to disseminate the skills required to perform BASILICA, according to Dr. Khan, who explained that proctors typically participate in two or three cases before these are performed without supervision.

So far, the uptake of BASILICA has been limited.

“BASILICA has not been catching on in EUROPE,” said Didier F. Loulmet, MD, chief of cardiac surgery at Tisch Hospital, New York University Langone Health. There might be several reasons, but Dr. Loulmet said that lack of a comparable proctoring program is one factor.”

“This is a relatively complex procedure performed in a small number of patients, so building up expertise is quite a challenge, particularly in small centers,” he added. He encouraged proctoring as “the way that it has to be propagated.”

The results presented by Dr. Khan on March 6 at CRT 2021 were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Khan has patents on several devices, including catheters to lacerate valve leaflet. Dr. Loulmet reported no potential conflicts of interest.

Direct oral anticoagulants (DOACs) are used in about 1% of patients undergoing surgical mechanical aortic and mitral valve replacement, but in up to 6% of surgical bioprosthetic valve replacements, according to registry data presented at CRT 2021.

In an analysis of the Society of Thoracic Surgery (STS) registry during 2014-2017, DOAC use increased steadily among those undergoing surgical bioprosthetic valve replacement, reaching a number that is potentially clinically significant, according to Ankur Kalra, MD, an interventional cardiologist at Akron General Hospital who has an academic appointment at the Cleveland Clinic.

There was no increase in the use of DOACs observed among patients undergoing mechanical valve replacement, “but even if the number is 1%, they should probably not be used at all until we accrue more data,” Dr. Kalra said.
 

DOACs discouraged in patients with mechanical or bioprosthetic valves

In Food and Drug Administration labeling, DOACs are contraindicated or not recommended. This can be traced to the randomized RE-ALIGN trial, which was stopped prematurely due to evidence of harm from a DOAC, according to Dr. Kalra.

In RE-ALIGN, which enrolled patients undergoing mechanical aortic or mitral valve replacement, dabigatran was associated not only with more bleeding events than warfarin, but also more thromboembolic events.

There are no randomized data comparing the factor Xa inhibitors rivaroxaban or apixaban to warfarin in heart valve surgery, but Dr. Kalra noted cautionary language is found in the labeling of both, “perhaps due to the RE-ALIGN data.”
 

Registry shows trends in prescribing

In the STS registry data, 193 (1.1%) of the 18,142 patients undergoing mechanical aortic valve surgery, 139 (1.0%) of the 13,942 patients undergoing mechanical mitral valve surgery, 5,625 (4.7%) of the 116,203 patients undergoing aortic bioprosthetic aortic valve surgery, and 2,180 (5.9%) of the 39,243 patients undergoing bioprosthetic mitral valve surgery were on a DOAC at discharge.

Among those receiving a mechanical value and placed on a DOAC, about two-thirds were on a factor Xa inhibitor rather than dabigatran. For those receiving a bioprosthetic value, the proportion was greater than 80%. Dr. Kalra speculated that the RE-ALIGN trial might be the reason factor Xa inhibitors were favored.

In both types of valves, whether mechanical or bioprosthetic, more comorbidities predicted a greater likelihood of receiving a DOAC rather than warfarin. For those receiving mechanical values, the comorbidities with a significant association with greater DOAC use included hypertension (P = .003), dyslipidemia (P = .02), arrhythmia (P < .001), and peripheral arterial disease (P < 0.001).

The same factors were significant for predicting increased likelihood of a DOAC following bioprosthetic valve replacement, but there were additional factors, including atrial fibrillation independent of other types of arrhythmias (P < .001), a factor not significant for mechanical valves, as well as diabetes (P < .001), cerebrovascular disease (P < .001), dialysis (P < .001), and endocarditis (P < .001).

“This is probably intuitive, but patients who were on a factor Xa inhibitor before their valve replacement were also more likely to be discharged on a factor Xa inhibitor,” Dr. Kalra said at the virtual meeting, sponsored by MedStar Heart & Vascular Institute.

The year-to-year increase in DOAC use among those undergoing bioprosthetic valve replacement over the study period, which was a significant trend, was not observed among those undergoing mechanical valve replacement. Rather, the 1% proportion remained stable over the study period.

“We wanted to look at outcomes, but we found that the STS database, which only includes data out to 30 days, is not structured for this type of analysis,” Dr. Kalra said. He was also concerned about the limitations of a comparison in which 1% of the sample was being compared to 99%.
 

Expert: One percent is ‘very small number’

David J. Cohen, MD, commented on the 1% figure, which was so low that a moderator questioned whether it could be due mostly to coding errors.

“This is a very, very small number so at some level it is reassuring that it is so low in the mechanical valves,” Dr. Cohen said. However, he was more circumspect about the larger number in bioprosthetic valves.

“I have always thought it was a bit strange there was a warning against using them in bioprosthetic valves, especially in the aortic position,” he said.

Direct oral anticoagulants (DOACs) are used in about 1% of patients undergoing surgical mechanical aortic and mitral valve replacement, but in up to 6% of surgical bioprosthetic valve replacements, according to registry data presented at CRT 2021.

In an analysis of the Society of Thoracic Surgery (STS) registry during 2014-2017, DOAC use increased steadily among those undergoing surgical bioprosthetic valve replacement, reaching a number that is potentially clinically significant, according to Ankur Kalra, MD, an interventional cardiologist at Akron General Hospital who has an academic appointment at the Cleveland Clinic.

There was no increase in the use of DOACs observed among patients undergoing mechanical valve replacement, “but even if the number is 1%, they should probably not be used at all until we accrue more data,” Dr. Kalra said.
 

DOACs discouraged in patients with mechanical or bioprosthetic valves

In Food and Drug Administration labeling, DOACs are contraindicated or not recommended. This can be traced to the randomized RE-ALIGN trial, which was stopped prematurely due to evidence of harm from a DOAC, according to Dr. Kalra.

In RE-ALIGN, which enrolled patients undergoing mechanical aortic or mitral valve replacement, dabigatran was associated not only with more bleeding events than warfarin, but also more thromboembolic events.

There are no randomized data comparing the factor Xa inhibitors rivaroxaban or apixaban to warfarin in heart valve surgery, but Dr. Kalra noted cautionary language is found in the labeling of both, “perhaps due to the RE-ALIGN data.”
 

Registry shows trends in prescribing

In the STS registry data, 193 (1.1%) of the 18,142 patients undergoing mechanical aortic valve surgery, 139 (1.0%) of the 13,942 patients undergoing mechanical mitral valve surgery, 5,625 (4.7%) of the 116,203 patients undergoing aortic bioprosthetic aortic valve surgery, and 2,180 (5.9%) of the 39,243 patients undergoing bioprosthetic mitral valve surgery were on a DOAC at discharge.

Among those receiving a mechanical value and placed on a DOAC, about two-thirds were on a factor Xa inhibitor rather than dabigatran. For those receiving a bioprosthetic value, the proportion was greater than 80%. Dr. Kalra speculated that the RE-ALIGN trial might be the reason factor Xa inhibitors were favored.

In both types of valves, whether mechanical or bioprosthetic, more comorbidities predicted a greater likelihood of receiving a DOAC rather than warfarin. For those receiving mechanical values, the comorbidities with a significant association with greater DOAC use included hypertension (P = .003), dyslipidemia (P = .02), arrhythmia (P < .001), and peripheral arterial disease (P < 0.001).

The same factors were significant for predicting increased likelihood of a DOAC following bioprosthetic valve replacement, but there were additional factors, including atrial fibrillation independent of other types of arrhythmias (P < .001), a factor not significant for mechanical valves, as well as diabetes (P < .001), cerebrovascular disease (P < .001), dialysis (P < .001), and endocarditis (P < .001).

“This is probably intuitive, but patients who were on a factor Xa inhibitor before their valve replacement were also more likely to be discharged on a factor Xa inhibitor,” Dr. Kalra said at the virtual meeting, sponsored by MedStar Heart & Vascular Institute.

The year-to-year increase in DOAC use among those undergoing bioprosthetic valve replacement over the study period, which was a significant trend, was not observed among those undergoing mechanical valve replacement. Rather, the 1% proportion remained stable over the study period.

“We wanted to look at outcomes, but we found that the STS database, which only includes data out to 30 days, is not structured for this type of analysis,” Dr. Kalra said. He was also concerned about the limitations of a comparison in which 1% of the sample was being compared to 99%.
 

Expert: One percent is ‘very small number’

David J. Cohen, MD, commented on the 1% figure, which was so low that a moderator questioned whether it could be due mostly to coding errors.

“This is a very, very small number so at some level it is reassuring that it is so low in the mechanical valves,” Dr. Cohen said. However, he was more circumspect about the larger number in bioprosthetic valves.

“I have always thought it was a bit strange there was a warning against using them in bioprosthetic valves, especially in the aortic position,” he said.

Direct oral anticoagulants (DOACs) are used in about 1% of patients undergoing surgical mechanical aortic and mitral valve replacement, but in up to 6% of surgical bioprosthetic valve replacements, according to registry data presented at CRT 2021.

In an analysis of the Society of Thoracic Surgery (STS) registry during 2014-2017, DOAC use increased steadily among those undergoing surgical bioprosthetic valve replacement, reaching a number that is potentially clinically significant, according to Ankur Kalra, MD, an interventional cardiologist at Akron General Hospital who has an academic appointment at the Cleveland Clinic.

There was no increase in the use of DOACs observed among patients undergoing mechanical valve replacement, “but even if the number is 1%, they should probably not be used at all until we accrue more data,” Dr. Kalra said.
 

DOACs discouraged in patients with mechanical or bioprosthetic valves

In Food and Drug Administration labeling, DOACs are contraindicated or not recommended. This can be traced to the randomized RE-ALIGN trial, which was stopped prematurely due to evidence of harm from a DOAC, according to Dr. Kalra.

In RE-ALIGN, which enrolled patients undergoing mechanical aortic or mitral valve replacement, dabigatran was associated not only with more bleeding events than warfarin, but also more thromboembolic events.

There are no randomized data comparing the factor Xa inhibitors rivaroxaban or apixaban to warfarin in heart valve surgery, but Dr. Kalra noted cautionary language is found in the labeling of both, “perhaps due to the RE-ALIGN data.”
 

Registry shows trends in prescribing

In the STS registry data, 193 (1.1%) of the 18,142 patients undergoing mechanical aortic valve surgery, 139 (1.0%) of the 13,942 patients undergoing mechanical mitral valve surgery, 5,625 (4.7%) of the 116,203 patients undergoing aortic bioprosthetic aortic valve surgery, and 2,180 (5.9%) of the 39,243 patients undergoing bioprosthetic mitral valve surgery were on a DOAC at discharge.

Among those receiving a mechanical value and placed on a DOAC, about two-thirds were on a factor Xa inhibitor rather than dabigatran. For those receiving a bioprosthetic value, the proportion was greater than 80%. Dr. Kalra speculated that the RE-ALIGN trial might be the reason factor Xa inhibitors were favored.

In both types of valves, whether mechanical or bioprosthetic, more comorbidities predicted a greater likelihood of receiving a DOAC rather than warfarin. For those receiving mechanical values, the comorbidities with a significant association with greater DOAC use included hypertension (P = .003), dyslipidemia (P = .02), arrhythmia (P < .001), and peripheral arterial disease (P < 0.001).

The same factors were significant for predicting increased likelihood of a DOAC following bioprosthetic valve replacement, but there were additional factors, including atrial fibrillation independent of other types of arrhythmias (P < .001), a factor not significant for mechanical valves, as well as diabetes (P < .001), cerebrovascular disease (P < .001), dialysis (P < .001), and endocarditis (P < .001).

“This is probably intuitive, but patients who were on a factor Xa inhibitor before their valve replacement were also more likely to be discharged on a factor Xa inhibitor,” Dr. Kalra said at the virtual meeting, sponsored by MedStar Heart & Vascular Institute.

The year-to-year increase in DOAC use among those undergoing bioprosthetic valve replacement over the study period, which was a significant trend, was not observed among those undergoing mechanical valve replacement. Rather, the 1% proportion remained stable over the study period.

“We wanted to look at outcomes, but we found that the STS database, which only includes data out to 30 days, is not structured for this type of analysis,” Dr. Kalra said. He was also concerned about the limitations of a comparison in which 1% of the sample was being compared to 99%.
 

Expert: One percent is ‘very small number’

David J. Cohen, MD, commented on the 1% figure, which was so low that a moderator questioned whether it could be due mostly to coding errors.

“This is a very, very small number so at some level it is reassuring that it is so low in the mechanical valves,” Dr. Cohen said. However, he was more circumspect about the larger number in bioprosthetic valves.

“I have always thought it was a bit strange there was a warning against using them in bioprosthetic valves, especially in the aortic position,” he said.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.

“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
 

Sexes share key symptoms, but not treatment

Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.

There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.

Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.

In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.

“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
 

Additional symptoms may muddy the diagnostic waters

In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.

In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.

In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).

There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
 

‘Yentl syndrome’ persists

“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.

Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.

This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.

The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.

“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.

“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
 

Sexes share key symptoms, but not treatment

Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.

There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.

Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.

In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.

“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
 

Additional symptoms may muddy the diagnostic waters

In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.

In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.

In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).

There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
 

‘Yentl syndrome’ persists

“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.

Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.

This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.

The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.

“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.

“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
 

Sexes share key symptoms, but not treatment

Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.

There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.

Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.

In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.

“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
 

Additional symptoms may muddy the diagnostic waters

In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.

In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.

In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).

There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
 

‘Yentl syndrome’ persists

“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.

Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.

This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.

The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.

“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Bimekizumab, an experimental biologic for the treatment of psoriasis that inhibits both interleukin-17A and IL-17F, achieves rates of skin clearance greater than those reported in phase 3 trials with other biologics, according to data from two simultaneously published trials, one of which was a head-to-head comparison with ustekinumab.

In the head-to-head trial called BE VIVID, which included a placebo arm, there was a large advantage of bimekizumab over ustekinumab, a biologic that targets IL-12 and IL-23 and is approved for treating psoriasis, for both coprimary endpoints, according to a multinational group of investigators led by Kristian Reich, MD, PhD, professor of dermatology at the University Medical Center, Hamburg-Eppendorf, Germany.

The proportion of patients with skin clearance was not only greater but faster, “with responses observed after one dose,” Dr. Reich and coinvestigators reported.

The data from the BE VIVID trial was published simultaneously with the BE READY trial, which was placebo-controlled but did not include an active comparator.

Evaluated at week 16, the coprimary endpoints in both studies were skin clearance as measured by a Psoriasis Area Severity Index greater than 90% (PASI 90) and Investigators Global Assessment (IGA) score of 0 (clear) or 1 (almost clear).

In BE VIVID, 567 patients were randomized in 11 countries, including the United States. The dose of bimekizumab was 320 mg administered subcutaneously every 4 weeks. In a randomization scheme of 4:2:1, half as many patients (163) were randomized to ustekinumab (Stelara), which was administered in weight-based dosing of 45 mg or 90 mg at enrollment, at 4 weeks, and then every 12 weeks. The placebo arm had 83 patients. All were switched to bimekizumab at 16 weeks.

At week 16, PASI 90 was achieved in 85% of patients randomized to bimekizumab, compared with 50% of patients randomized to ustekinumab (P < .0001). The rate in the placebo group was 5%.

The bimekizumab advantage for an IGA response of 0 or 1 was of similar magnitude, relative to ustekinumab (84% vs. 53%; P < .0001) and placebo (5%). All secondary efficacy endpoints, such as PASI 90 at week 12 (85% vs. 44%) and PASI 100 at week 16 (59% vs. 21%), favored bimekizumab over ustekinumab.

In the BE READY trial, which evaluated the same dose and schedule of bimekizumab, the rates of PASI 90 at week 16 were 91% and 1% (P < .0001) for the experimental arm and placebo, respectively. The proportion of patients with an IGA score of 0 or 1 were 93% and 1% (P < .0001), respectively.

In BE READY, patients who achieved PASI 90 at week 16 were reallocated to receive bimekizumab every 4 weeks, bimekizumab every 8 weeks (also 320 mg), or placebo. Both schedules of bimekizumab maintained responses through week 56, according to the authors, led by Kenneth B. Gordon, MD, professor and chair of dermatology, Medical College of Wisconsin, Milwaukee.

In both trials, safety was evaluated over the first 16 weeks as well as over a subsequent maintenance period, which extended to 52 weeks in BE VIVID and 56 weeks in BE READY. For bimekizumab, oral candidiasis was the most common treatment-related adverse event. In BE VIVID, this adverse event was reported in 9% of bimekizumab patients, compared with 0% of either the ustekinumab or placebo groups, up to week 16. Out to week 52, the rates were 15% in the bimekizumab group and 1% in the ustekinumab group.

In the BE READY trial, the rates of oral candidiasis were 6% and 0% for bimekizumab and placebo, respectively, through week 16. Over the maintenance periods, the rates were 9% and 11% for the every-8-week and every-4-week doses, respectively.

Discontinuation for adverse events was not higher on bimekizumab than placebo in either trial, nor was the proportion of serious treatment-emergent adverse events.

Nevertheless, the potential for adverse events was a key part of the discussion regarding the future role of bimekizumab, if approved, in an editorial that accompanied the publication of these studies.

“Bimekizumab might be our most effective biologic for psoriasis yet,” coauthors, William W. Huang, MD, PhD, associate professor of dermatology, and Steven R. Feldman, MD, PhD, professor of dermatology, both at Wake Forest University, Winston-Salem, NC, wrote in the editorial. “If the goal of psoriasis treatment is complete clearance, bimekizumab seems like a good option from an efficacy perspective.”

However, they noted that other IL-17 blockers, like secukinumab (Cosentyx) and brodalumab (Siliq), have been associated with risks, including the development of inflammatory bowel disease. In addition to the oral candidiasis seen in the BE VIVID and BE READY trials, they cautioned that other issues might arise with longer follow-up and greater numbers of patients exposed to this therapy.

In an interview, Dr. Feldman said adequately informed patients might be willing to accept these risks for the potential of greater efficacy, but he emphasized the need for appropriate warnings and education.

“We have a lot of very good treatments that offer patients an excellent chance of an excellent outcome – treatments that have been around and in use in large numbers of people for years,” Dr. Feldman said. “Unless the doctor and patient felt strongly about the need to use this new, perhaps more potent option, I would be personally inclined to use treatment with well-established safety profiles first.”

The senior author of the BE VIVID trial, Mark Lebwohl, MD, dean for clinical therapeutics and professor of dermatology, at the Icahn School of Medicine at Mount Sinai, New York, disagreed. He acknowledged that other agents targeting IL-17 have been associated with IBD, but risk of IBD is already elevated in patients with psoriasis and the risk appears to be lower with bimekizumab relative to prior agents in this class.

“Bimekizumab has now been studied in thousands of patients over several years. We can say with support from a sizable amount of data that IBD is very uncommon,” he said. While oral candidiasis is associated with bimekizumab, it is “easy to treat.”

Asked specifically if he will consider using bimekizumab as a first-line agent in psoriasis patients who are candidates for a biologic, Dr. Lebwohl said he would. Based on the evidence that this agent is more effective than other options and has manageable side effects, he believes it will be an important new treatment option.

Dr. Reich, Dr. Lebwohl, Dr. Gordon, and Dr. Feldman have financial relationships with multiple companies that produce therapies for psoriasis, including UCB Pharma, the sponsor of these studies.
 

Bimekizumab, an experimental biologic for the treatment of psoriasis that inhibits both interleukin-17A and IL-17F, achieves rates of skin clearance greater than those reported in phase 3 trials with other biologics, according to data from two simultaneously published trials, one of which was a head-to-head comparison with ustekinumab.

In the head-to-head trial called BE VIVID, which included a placebo arm, there was a large advantage of bimekizumab over ustekinumab, a biologic that targets IL-12 and IL-23 and is approved for treating psoriasis, for both coprimary endpoints, according to a multinational group of investigators led by Kristian Reich, MD, PhD, professor of dermatology at the University Medical Center, Hamburg-Eppendorf, Germany.

The proportion of patients with skin clearance was not only greater but faster, “with responses observed after one dose,” Dr. Reich and coinvestigators reported.

The data from the BE VIVID trial was published simultaneously with the BE READY trial, which was placebo-controlled but did not include an active comparator.

Evaluated at week 16, the coprimary endpoints in both studies were skin clearance as measured by a Psoriasis Area Severity Index greater than 90% (PASI 90) and Investigators Global Assessment (IGA) score of 0 (clear) or 1 (almost clear).

In BE VIVID, 567 patients were randomized in 11 countries, including the United States. The dose of bimekizumab was 320 mg administered subcutaneously every 4 weeks. In a randomization scheme of 4:2:1, half as many patients (163) were randomized to ustekinumab (Stelara), which was administered in weight-based dosing of 45 mg or 90 mg at enrollment, at 4 weeks, and then every 12 weeks. The placebo arm had 83 patients. All were switched to bimekizumab at 16 weeks.

At week 16, PASI 90 was achieved in 85% of patients randomized to bimekizumab, compared with 50% of patients randomized to ustekinumab (P < .0001). The rate in the placebo group was 5%.

The bimekizumab advantage for an IGA response of 0 or 1 was of similar magnitude, relative to ustekinumab (84% vs. 53%; P < .0001) and placebo (5%). All secondary efficacy endpoints, such as PASI 90 at week 12 (85% vs. 44%) and PASI 100 at week 16 (59% vs. 21%), favored bimekizumab over ustekinumab.

In the BE READY trial, which evaluated the same dose and schedule of bimekizumab, the rates of PASI 90 at week 16 were 91% and 1% (P < .0001) for the experimental arm and placebo, respectively. The proportion of patients with an IGA score of 0 or 1 were 93% and 1% (P < .0001), respectively.

In BE READY, patients who achieved PASI 90 at week 16 were reallocated to receive bimekizumab every 4 weeks, bimekizumab every 8 weeks (also 320 mg), or placebo. Both schedules of bimekizumab maintained responses through week 56, according to the authors, led by Kenneth B. Gordon, MD, professor and chair of dermatology, Medical College of Wisconsin, Milwaukee.

In both trials, safety was evaluated over the first 16 weeks as well as over a subsequent maintenance period, which extended to 52 weeks in BE VIVID and 56 weeks in BE READY. For bimekizumab, oral candidiasis was the most common treatment-related adverse event. In BE VIVID, this adverse event was reported in 9% of bimekizumab patients, compared with 0% of either the ustekinumab or placebo groups, up to week 16. Out to week 52, the rates were 15% in the bimekizumab group and 1% in the ustekinumab group.

In the BE READY trial, the rates of oral candidiasis were 6% and 0% for bimekizumab and placebo, respectively, through week 16. Over the maintenance periods, the rates were 9% and 11% for the every-8-week and every-4-week doses, respectively.

Discontinuation for adverse events was not higher on bimekizumab than placebo in either trial, nor was the proportion of serious treatment-emergent adverse events.

Nevertheless, the potential for adverse events was a key part of the discussion regarding the future role of bimekizumab, if approved, in an editorial that accompanied the publication of these studies.

“Bimekizumab might be our most effective biologic for psoriasis yet,” coauthors, William W. Huang, MD, PhD, associate professor of dermatology, and Steven R. Feldman, MD, PhD, professor of dermatology, both at Wake Forest University, Winston-Salem, NC, wrote in the editorial. “If the goal of psoriasis treatment is complete clearance, bimekizumab seems like a good option from an efficacy perspective.”

However, they noted that other IL-17 blockers, like secukinumab (Cosentyx) and brodalumab (Siliq), have been associated with risks, including the development of inflammatory bowel disease. In addition to the oral candidiasis seen in the BE VIVID and BE READY trials, they cautioned that other issues might arise with longer follow-up and greater numbers of patients exposed to this therapy.

In an interview, Dr. Feldman said adequately informed patients might be willing to accept these risks for the potential of greater efficacy, but he emphasized the need for appropriate warnings and education.

“We have a lot of very good treatments that offer patients an excellent chance of an excellent outcome – treatments that have been around and in use in large numbers of people for years,” Dr. Feldman said. “Unless the doctor and patient felt strongly about the need to use this new, perhaps more potent option, I would be personally inclined to use treatment with well-established safety profiles first.”

The senior author of the BE VIVID trial, Mark Lebwohl, MD, dean for clinical therapeutics and professor of dermatology, at the Icahn School of Medicine at Mount Sinai, New York, disagreed. He acknowledged that other agents targeting IL-17 have been associated with IBD, but risk of IBD is already elevated in patients with psoriasis and the risk appears to be lower with bimekizumab relative to prior agents in this class.

“Bimekizumab has now been studied in thousands of patients over several years. We can say with support from a sizable amount of data that IBD is very uncommon,” he said. While oral candidiasis is associated with bimekizumab, it is “easy to treat.”

Asked specifically if he will consider using bimekizumab as a first-line agent in psoriasis patients who are candidates for a biologic, Dr. Lebwohl said he would. Based on the evidence that this agent is more effective than other options and has manageable side effects, he believes it will be an important new treatment option.

Dr. Reich, Dr. Lebwohl, Dr. Gordon, and Dr. Feldman have financial relationships with multiple companies that produce therapies for psoriasis, including UCB Pharma, the sponsor of these studies.
 

Bimekizumab, an experimental biologic for the treatment of psoriasis that inhibits both interleukin-17A and IL-17F, achieves rates of skin clearance greater than those reported in phase 3 trials with other biologics, according to data from two simultaneously published trials, one of which was a head-to-head comparison with ustekinumab.

In the head-to-head trial called BE VIVID, which included a placebo arm, there was a large advantage of bimekizumab over ustekinumab, a biologic that targets IL-12 and IL-23 and is approved for treating psoriasis, for both coprimary endpoints, according to a multinational group of investigators led by Kristian Reich, MD, PhD, professor of dermatology at the University Medical Center, Hamburg-Eppendorf, Germany.

The proportion of patients with skin clearance was not only greater but faster, “with responses observed after one dose,” Dr. Reich and coinvestigators reported.

The data from the BE VIVID trial was published simultaneously with the BE READY trial, which was placebo-controlled but did not include an active comparator.

Evaluated at week 16, the coprimary endpoints in both studies were skin clearance as measured by a Psoriasis Area Severity Index greater than 90% (PASI 90) and Investigators Global Assessment (IGA) score of 0 (clear) or 1 (almost clear).

In BE VIVID, 567 patients were randomized in 11 countries, including the United States. The dose of bimekizumab was 320 mg administered subcutaneously every 4 weeks. In a randomization scheme of 4:2:1, half as many patients (163) were randomized to ustekinumab (Stelara), which was administered in weight-based dosing of 45 mg or 90 mg at enrollment, at 4 weeks, and then every 12 weeks. The placebo arm had 83 patients. All were switched to bimekizumab at 16 weeks.

At week 16, PASI 90 was achieved in 85% of patients randomized to bimekizumab, compared with 50% of patients randomized to ustekinumab (P < .0001). The rate in the placebo group was 5%.

The bimekizumab advantage for an IGA response of 0 or 1 was of similar magnitude, relative to ustekinumab (84% vs. 53%; P < .0001) and placebo (5%). All secondary efficacy endpoints, such as PASI 90 at week 12 (85% vs. 44%) and PASI 100 at week 16 (59% vs. 21%), favored bimekizumab over ustekinumab.

In the BE READY trial, which evaluated the same dose and schedule of bimekizumab, the rates of PASI 90 at week 16 were 91% and 1% (P < .0001) for the experimental arm and placebo, respectively. The proportion of patients with an IGA score of 0 or 1 were 93% and 1% (P < .0001), respectively.

In BE READY, patients who achieved PASI 90 at week 16 were reallocated to receive bimekizumab every 4 weeks, bimekizumab every 8 weeks (also 320 mg), or placebo. Both schedules of bimekizumab maintained responses through week 56, according to the authors, led by Kenneth B. Gordon, MD, professor and chair of dermatology, Medical College of Wisconsin, Milwaukee.

In both trials, safety was evaluated over the first 16 weeks as well as over a subsequent maintenance period, which extended to 52 weeks in BE VIVID and 56 weeks in BE READY. For bimekizumab, oral candidiasis was the most common treatment-related adverse event. In BE VIVID, this adverse event was reported in 9% of bimekizumab patients, compared with 0% of either the ustekinumab or placebo groups, up to week 16. Out to week 52, the rates were 15% in the bimekizumab group and 1% in the ustekinumab group.

In the BE READY trial, the rates of oral candidiasis were 6% and 0% for bimekizumab and placebo, respectively, through week 16. Over the maintenance periods, the rates were 9% and 11% for the every-8-week and every-4-week doses, respectively.

Discontinuation for adverse events was not higher on bimekizumab than placebo in either trial, nor was the proportion of serious treatment-emergent adverse events.

Nevertheless, the potential for adverse events was a key part of the discussion regarding the future role of bimekizumab, if approved, in an editorial that accompanied the publication of these studies.

“Bimekizumab might be our most effective biologic for psoriasis yet,” coauthors, William W. Huang, MD, PhD, associate professor of dermatology, and Steven R. Feldman, MD, PhD, professor of dermatology, both at Wake Forest University, Winston-Salem, NC, wrote in the editorial. “If the goal of psoriasis treatment is complete clearance, bimekizumab seems like a good option from an efficacy perspective.”

However, they noted that other IL-17 blockers, like secukinumab (Cosentyx) and brodalumab (Siliq), have been associated with risks, including the development of inflammatory bowel disease. In addition to the oral candidiasis seen in the BE VIVID and BE READY trials, they cautioned that other issues might arise with longer follow-up and greater numbers of patients exposed to this therapy.

In an interview, Dr. Feldman said adequately informed patients might be willing to accept these risks for the potential of greater efficacy, but he emphasized the need for appropriate warnings and education.

“We have a lot of very good treatments that offer patients an excellent chance of an excellent outcome – treatments that have been around and in use in large numbers of people for years,” Dr. Feldman said. “Unless the doctor and patient felt strongly about the need to use this new, perhaps more potent option, I would be personally inclined to use treatment with well-established safety profiles first.”

The senior author of the BE VIVID trial, Mark Lebwohl, MD, dean for clinical therapeutics and professor of dermatology, at the Icahn School of Medicine at Mount Sinai, New York, disagreed. He acknowledged that other agents targeting IL-17 have been associated with IBD, but risk of IBD is already elevated in patients with psoriasis and the risk appears to be lower with bimekizumab relative to prior agents in this class.

“Bimekizumab has now been studied in thousands of patients over several years. We can say with support from a sizable amount of data that IBD is very uncommon,” he said. While oral candidiasis is associated with bimekizumab, it is “easy to treat.”

Asked specifically if he will consider using bimekizumab as a first-line agent in psoriasis patients who are candidates for a biologic, Dr. Lebwohl said he would. Based on the evidence that this agent is more effective than other options and has manageable side effects, he believes it will be an important new treatment option.

Dr. Reich, Dr. Lebwohl, Dr. Gordon, and Dr. Feldman have financial relationships with multiple companies that produce therapies for psoriasis, including UCB Pharma, the sponsor of these studies.
 

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Although not correlated with each other, increased levels of circulating neprilysin and corin concentrations correlate with increased risk of cardiovascular death and heart failure hospitalizations in chronic heart failure (CHF) patients, according to prospective analysis involving 1,009 HF patients.

This implies that these enzymes might have value for individualizing care, including treatment of patients in heart failure with preserved ejection fraction (HFpEF), reported a team of investigators led by D.H. Frank Gommans, MD, PhD, department of cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

When followed for up to 7 years and after adjustment for differences in sex and age, the highest risk for the primary composite endpoint of cardiovascular (CV) death and heart failure hospitalization was observed in those with both high soluble neprilysin (sNEP) and high soluble corin (sCOR). The lowest risk was observed in the group with low levels of both enzymes.

The data suggest that monitoring these enzymes might provide “a step toward individualized CHF patient management,” Dr. Gommans reported in JACC Heart Failure, the adjusted hazard ratio for elevated sNEP and sCOR translated into a greater than 50% increase in the composite primary endpoint relative to low levels of both (HR, 1.56; P = .003). After a “comprehensive multivariable analysis,” the increased risk remained substantial and significant (HR, 1.41; P = .03).

In the natriuretic peptide pathway, which has long been recognized as a mediator of vasodilation, venous compliance, diuresis, and other processes dysregulated in heart failure, NEP and COR are “key mediators,” according to the investigators, who cited previously published studies. More attention has turned to these enzymes as potential biomarkers in the context of the PARADIGM trial, which associated an angiotensin-receptor neprilysin inhibitor (ARNI) with a survival benefit in CHF.

The observational study consisted of CHF patients attending a heart failure clinic and who were ARNI naive at inclusion. On the basis of circulating enzyme measurements undertaken from blood samples employing standard techniques, they were stratified into four groups. Those with low levels of both enzymes served as the reference. They were compared with those with low sNEP and high sCOR, those with high sNEP and low sCOR, and those with high levels of both enzymes.

Over the course of a median 4.5 years of follow-up, there were 511 deaths, of which 54% were from a CV cause. There were also 331 heart failure hospitalizations. In all, 449 patients reached the primary composite endpoint.

When compared with the group with low sNEP and low sCOR, an elevation in either enzyme was associated with a numerically but not significantly greater hazard ratio for the primary composite endpoint. The lack of correlation in the elevation of these two enzymes suggests each provides different prognostic information, although it appears that both must be considered together to predict outcomes.

Clinically, stratification of these enzymes might be most useful in HFpEF patients. Relative to the separation of event curves in the CHF patients with reduced ejection fraction (HFrEF), the divergence in the event curves for HFpEF were greater. In addition, event curves separated from the reference in HFpEF patients but not the HFrEF patients if either enzyme was elevated.

Asked if these data hold particular promise for monitoring and individualizing therapy in HFpEF patients, Dr. Gommans said yes. Although he cautioned that this was an observational study and that the differences between the HFpEF and HFrEF should be considered exploratory, he agreed that components of the natriuretic peptide pathway have particular potential to provide new prognostic information and individualize care in HFpEF, where therapeutic options remain limited.

Stratification of natriuretic peptide enzymes in this group might “present as an interesting alternative to ejection fraction” for prognosis and the consideration of treatment choices, he suggested.

Although further validation of the prognostic importance of sNEP and sCOR is needed, according to Dr. Gommans, he foresees the potential of therapeutic trials based on elevated levels of these enzymes. For example, he speculated that these levels might distinguish HFpEF patients who could benefit from a first-line ARNI.

In an accompanying editorial, significant doubts were expressed about simple measurements of sNEP and sCOR concentrations to predict clinical course or guide treatment decisions. The authors of the editorial agreed this is an important area of study but warned of its complexity.

“Concentrations of circulating neprilysin have been shown to correlate poorly with neprilysin activity. Thus the rate of natriuretic peptide degradation by neprilysin cannot be determined solely by measuring circulating levels,” cautioned Peder L. Myhre, MD, PhD, who is a cardiology fellow at Akershus University Hospital in Nordbyhagen, Norway, and postdoc researcher at the University of Oslo.

“Accordingly, concentrations of neprilysin and corin cannot alone be used to predict response to therapies interacting with these peptides,” he added. He agreed that neprilysin and corin might be appropriate biomarkers in CHF, but he thinks the focus must be on their enzymatic activity, not their circulating levels.

“Measuring the enzymatic activity may be a feasible strategy, but this remains to be seen,” he said.

Dr. Gommans reported a financial relationship with Novartis. Dr. Myhre reported financial relationships with Amgen, Novartis, and Novo Nordisk.

Although not correlated with each other, increased levels of circulating neprilysin and corin concentrations correlate with increased risk of cardiovascular death and heart failure hospitalizations in chronic heart failure (CHF) patients, according to prospective analysis involving 1,009 HF patients.

This implies that these enzymes might have value for individualizing care, including treatment of patients in heart failure with preserved ejection fraction (HFpEF), reported a team of investigators led by D.H. Frank Gommans, MD, PhD, department of cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

When followed for up to 7 years and after adjustment for differences in sex and age, the highest risk for the primary composite endpoint of cardiovascular (CV) death and heart failure hospitalization was observed in those with both high soluble neprilysin (sNEP) and high soluble corin (sCOR). The lowest risk was observed in the group with low levels of both enzymes.

The data suggest that monitoring these enzymes might provide “a step toward individualized CHF patient management,” Dr. Gommans reported in JACC Heart Failure, the adjusted hazard ratio for elevated sNEP and sCOR translated into a greater than 50% increase in the composite primary endpoint relative to low levels of both (HR, 1.56; P = .003). After a “comprehensive multivariable analysis,” the increased risk remained substantial and significant (HR, 1.41; P = .03).

In the natriuretic peptide pathway, which has long been recognized as a mediator of vasodilation, venous compliance, diuresis, and other processes dysregulated in heart failure, NEP and COR are “key mediators,” according to the investigators, who cited previously published studies. More attention has turned to these enzymes as potential biomarkers in the context of the PARADIGM trial, which associated an angiotensin-receptor neprilysin inhibitor (ARNI) with a survival benefit in CHF.

The observational study consisted of CHF patients attending a heart failure clinic and who were ARNI naive at inclusion. On the basis of circulating enzyme measurements undertaken from blood samples employing standard techniques, they were stratified into four groups. Those with low levels of both enzymes served as the reference. They were compared with those with low sNEP and high sCOR, those with high sNEP and low sCOR, and those with high levels of both enzymes.

Over the course of a median 4.5 years of follow-up, there were 511 deaths, of which 54% were from a CV cause. There were also 331 heart failure hospitalizations. In all, 449 patients reached the primary composite endpoint.

When compared with the group with low sNEP and low sCOR, an elevation in either enzyme was associated with a numerically but not significantly greater hazard ratio for the primary composite endpoint. The lack of correlation in the elevation of these two enzymes suggests each provides different prognostic information, although it appears that both must be considered together to predict outcomes.

Clinically, stratification of these enzymes might be most useful in HFpEF patients. Relative to the separation of event curves in the CHF patients with reduced ejection fraction (HFrEF), the divergence in the event curves for HFpEF were greater. In addition, event curves separated from the reference in HFpEF patients but not the HFrEF patients if either enzyme was elevated.

Asked if these data hold particular promise for monitoring and individualizing therapy in HFpEF patients, Dr. Gommans said yes. Although he cautioned that this was an observational study and that the differences between the HFpEF and HFrEF should be considered exploratory, he agreed that components of the natriuretic peptide pathway have particular potential to provide new prognostic information and individualize care in HFpEF, where therapeutic options remain limited.

Stratification of natriuretic peptide enzymes in this group might “present as an interesting alternative to ejection fraction” for prognosis and the consideration of treatment choices, he suggested.

Although further validation of the prognostic importance of sNEP and sCOR is needed, according to Dr. Gommans, he foresees the potential of therapeutic trials based on elevated levels of these enzymes. For example, he speculated that these levels might distinguish HFpEF patients who could benefit from a first-line ARNI.

In an accompanying editorial, significant doubts were expressed about simple measurements of sNEP and sCOR concentrations to predict clinical course or guide treatment decisions. The authors of the editorial agreed this is an important area of study but warned of its complexity.

“Concentrations of circulating neprilysin have been shown to correlate poorly with neprilysin activity. Thus the rate of natriuretic peptide degradation by neprilysin cannot be determined solely by measuring circulating levels,” cautioned Peder L. Myhre, MD, PhD, who is a cardiology fellow at Akershus University Hospital in Nordbyhagen, Norway, and postdoc researcher at the University of Oslo.

“Accordingly, concentrations of neprilysin and corin cannot alone be used to predict response to therapies interacting with these peptides,” he added. He agreed that neprilysin and corin might be appropriate biomarkers in CHF, but he thinks the focus must be on their enzymatic activity, not their circulating levels.

“Measuring the enzymatic activity may be a feasible strategy, but this remains to be seen,” he said.

Dr. Gommans reported a financial relationship with Novartis. Dr. Myhre reported financial relationships with Amgen, Novartis, and Novo Nordisk.

Although not correlated with each other, increased levels of circulating neprilysin and corin concentrations correlate with increased risk of cardiovascular death and heart failure hospitalizations in chronic heart failure (CHF) patients, according to prospective analysis involving 1,009 HF patients.

This implies that these enzymes might have value for individualizing care, including treatment of patients in heart failure with preserved ejection fraction (HFpEF), reported a team of investigators led by D.H. Frank Gommans, MD, PhD, department of cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

When followed for up to 7 years and after adjustment for differences in sex and age, the highest risk for the primary composite endpoint of cardiovascular (CV) death and heart failure hospitalization was observed in those with both high soluble neprilysin (sNEP) and high soluble corin (sCOR). The lowest risk was observed in the group with low levels of both enzymes.

The data suggest that monitoring these enzymes might provide “a step toward individualized CHF patient management,” Dr. Gommans reported in JACC Heart Failure, the adjusted hazard ratio for elevated sNEP and sCOR translated into a greater than 50% increase in the composite primary endpoint relative to low levels of both (HR, 1.56; P = .003). After a “comprehensive multivariable analysis,” the increased risk remained substantial and significant (HR, 1.41; P = .03).

In the natriuretic peptide pathway, which has long been recognized as a mediator of vasodilation, venous compliance, diuresis, and other processes dysregulated in heart failure, NEP and COR are “key mediators,” according to the investigators, who cited previously published studies. More attention has turned to these enzymes as potential biomarkers in the context of the PARADIGM trial, which associated an angiotensin-receptor neprilysin inhibitor (ARNI) with a survival benefit in CHF.

The observational study consisted of CHF patients attending a heart failure clinic and who were ARNI naive at inclusion. On the basis of circulating enzyme measurements undertaken from blood samples employing standard techniques, they were stratified into four groups. Those with low levels of both enzymes served as the reference. They were compared with those with low sNEP and high sCOR, those with high sNEP and low sCOR, and those with high levels of both enzymes.

Over the course of a median 4.5 years of follow-up, there were 511 deaths, of which 54% were from a CV cause. There were also 331 heart failure hospitalizations. In all, 449 patients reached the primary composite endpoint.

When compared with the group with low sNEP and low sCOR, an elevation in either enzyme was associated with a numerically but not significantly greater hazard ratio for the primary composite endpoint. The lack of correlation in the elevation of these two enzymes suggests each provides different prognostic information, although it appears that both must be considered together to predict outcomes.

Clinically, stratification of these enzymes might be most useful in HFpEF patients. Relative to the separation of event curves in the CHF patients with reduced ejection fraction (HFrEF), the divergence in the event curves for HFpEF were greater. In addition, event curves separated from the reference in HFpEF patients but not the HFrEF patients if either enzyme was elevated.

Asked if these data hold particular promise for monitoring and individualizing therapy in HFpEF patients, Dr. Gommans said yes. Although he cautioned that this was an observational study and that the differences between the HFpEF and HFrEF should be considered exploratory, he agreed that components of the natriuretic peptide pathway have particular potential to provide new prognostic information and individualize care in HFpEF, where therapeutic options remain limited.

Stratification of natriuretic peptide enzymes in this group might “present as an interesting alternative to ejection fraction” for prognosis and the consideration of treatment choices, he suggested.

Although further validation of the prognostic importance of sNEP and sCOR is needed, according to Dr. Gommans, he foresees the potential of therapeutic trials based on elevated levels of these enzymes. For example, he speculated that these levels might distinguish HFpEF patients who could benefit from a first-line ARNI.

In an accompanying editorial, significant doubts were expressed about simple measurements of sNEP and sCOR concentrations to predict clinical course or guide treatment decisions. The authors of the editorial agreed this is an important area of study but warned of its complexity.

“Concentrations of circulating neprilysin have been shown to correlate poorly with neprilysin activity. Thus the rate of natriuretic peptide degradation by neprilysin cannot be determined solely by measuring circulating levels,” cautioned Peder L. Myhre, MD, PhD, who is a cardiology fellow at Akershus University Hospital in Nordbyhagen, Norway, and postdoc researcher at the University of Oslo.

“Accordingly, concentrations of neprilysin and corin cannot alone be used to predict response to therapies interacting with these peptides,” he added. He agreed that neprilysin and corin might be appropriate biomarkers in CHF, but he thinks the focus must be on their enzymatic activity, not their circulating levels.

“Measuring the enzymatic activity may be a feasible strategy, but this remains to be seen,” he said.

Dr. Gommans reported a financial relationship with Novartis. Dr. Myhre reported financial relationships with Amgen, Novartis, and Novo Nordisk.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.

The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.

The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.

A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.

“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.

SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.

A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.

The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.

The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.

A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.

“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.

SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.

A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.

The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.

The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.

A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.

“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.

SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.