Cardiology News

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.

However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.

The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.

It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.

On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.

The scientific statement was published online on in Circulation.

“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.

Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.  

In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.

Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.

In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.

Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.

In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.

But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
 

MIS-C: Rare but severe

The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.

In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.

As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.

Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.

However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.

Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.

The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.

The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.  

Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
 

COVID-19 vaccination

The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.

On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.  

For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.

But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.

The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.

“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”

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

Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.

However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.

The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.

It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.

On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.

The scientific statement was published online on in Circulation.

“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.

Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.  

In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.

Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.

In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.

Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.

In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.

But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
 

MIS-C: Rare but severe

The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.

In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.

As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.

Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.

However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.

Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.

The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.

The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.  

Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
 

COVID-19 vaccination

The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.

On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.  

For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.

But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.

The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.

“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”

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

Cardiovascular complications are uncommon for children and young adults after COVID-19 disease or SARS-CoV-2 infection, according to a new scientific statement from the American Heart Association.

However, the infection can cause some children and young people to experience arrhythmias, myocarditis, pericarditis, or multisystem inflammatory syndrome (MIS-C), a new condition identified during the pandemic, it notes.

The statement details what has been learned about how to treat, manage, and prevent cardiovascular complications associated with COVID-19 in children and young adults and calls for more research, including studies following the short- and long-term cardiovascular effects.

It also reports that COVID-19 vaccines have been found to prevent severe COVID-19 disease and decrease the risk of developing MIS-C by 91% among children ages 12-18 years.

On returning to sports, it says data suggest it is safe for young people with mild or asymptomatic COVID-19 to resume exercise after recovery from symptoms. For those with more serious infections, it recommends additional tests, including cardiac enzyme levels, electrocardiogram, and echocardiogram, before returning to sports or strenuous physical exercise.

The scientific statement was published online on in Circulation.

“Two years into the pandemic and with vast amounts of research conducted in children with COVID-19, this statement summarizes what we know so far related to COVID-19 in children,” said chair of the statement writing group Pei-Ni Jone, MD, from the Children’s Hospital Colorado, Aurora.

Analysis of the latest research indicates children generally have mild symptoms from SARS-CoV-2 infection. In the U.S., as of Feb. 24, 2022, children under 18 years of age have accounted for 17.6% of total COVID-19 cases and about 0.1% of deaths from the virus, the report states.  

In addition, young adults, ages 18-29 years, have accounted for 21.3% of cases and 0.8% of deaths from COVID-19.

Like adults, children with underlying medical conditions such as chronic lung disease or obesity and those who are immunocompromised are more likely to be hospitalized, to be admitted to an intensive care unit, and to die of COVID-19, the statement notes. There are conflicting reports on the risk of severe COVID-19 in children and young adults with congenital heart disease, with some reports suggesting a slightly increased risk of severe COVID-19.

In terms of cardiovascular complications of COVID-19 in children, arrhythmias have included ventricular tachycardia and atrial tachycardia, as well as first-degree atrioventricular block. Although arrhythmias generally self-resolve without the need for treatment, prophylactic antiarrhythmics have been administered in some cases, and death caused by recurrent ventricular tachycardia in an adolescent with hypertrophic cardiomyopathy has been described.

Elevations of troponin, electrocardiographic abnormalities, including ST-segment changes, and delayed gadolinium enhancement on cardiac magnetic resonance imaging have been seen in those with myocardial involvement. Although death is rare, both sudden cardiac death and death after intensive medical and supportive therapies have occurred in children with severe myocardial involvement.

In a large retrospective pediatric case series of SARS-CoV-2–associated deaths in individuals under 21 years of age, the median age at death was 17 years, 63% were male, 28% were Black, and 46% were Hispanic. Of those who died, 86% had a comorbid condition, with obesity (42%) and asthma (29%) being the most common.

But the report concludes that: “Although children with comorbidities are at increased risk for symptomatic SARS-CoV-2 infection, compared with healthy children, cardiovascular complications, severe illness, and death are uncommon.”
 

MIS-C: Rare but severe

The authors of the statement explain that children and some young adults may develop MIS-C, a relatively rare but severe inflammatory syndrome generally occurring 2-6 weeks after infection with SARS-CoV-2 that can affect the heart and multiple organ systems.

In the first year of the pandemic, more than 2,600 cases of MIS-C were reported to the Centers for Disease Control and Prevention, at an estimated rate of 1 case per 3,164 cases of SARS-CoV-2 infection in children, with MIS-C disproportionately affecting Hispanic and Black children.

As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function, coronary artery dilation or aneurysms, myocarditis, elevated troponin and BNP or NT-proBNP, or pericardial effusion. Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C, neutrophil/lymphocyte ratio may be higher, and platelet counts lower than those with non–MIS-C febrile illnesses.

Fortunately, the outcome of MIS-C is generally very good, with resolution of inflammation and cardiovascular abnormalities within 1-4 weeks of diagnosis, the report says.

However, there have been reports of progression of coronary artery aneurysms after discharge, highlighting the potential for long-term complications. Death resulting from MIS-C is rare, with a mortality rate of 1.4%-1.9%.

Compared with children and young adults who died of acute SARS-CoV-2 infection, most of the fatalities from MIS-C were in previously healthy individuals without comorbidities.

The authors recommend structured follow-up of patients with MIS-C because of concern about progression of cardiac complications and an unclear long-term prognosis.

The statement notes that the first-line treatment for MIS-C is typically intravenous immunoglobulin (IVIG) and patients with poor ventricular function may need to have IVIG in divided doses to tolerate the fluid load.  

Supportive treatment for heart failure and vasoplegic shock often requires aggressive management in an ICU for administration of inotropes and vasoactive medications. Antiplatelet therapy with low-dose aspirin is considered in patients with coronary artery involvement, and anticoagulation is added, depending on the degree of coronary artery dilation.
 

COVID-19 vaccination

The statement notes that vaccines can prevent patients from getting COVID-19 and decrease the risk of MIS-C by 91% among children 12-18 years of age.

On vaccine-associated myocarditis, it concludes the benefits of getting the vaccines outweigh the risks.  

For example, for every 1 million doses of the mRNA COVID-19 vaccines in males ages 12-29 years (the highest risk group for vaccine-associated myocarditis), it is estimated that 11,000 COVID-19 cases, 560 hospitalizations, and six deaths would be prevented, whereas 39-47 cases of myocarditis would be expected.

But it adds that the CDC is continuing to follow myocarditis in children and young adults closely, particularly a possible connection to the mRNA COVID-19 vaccines.

The statement says that more research is needed to better understand the mechanisms and optimal treatment approaches for SARS-CoV-2 infection, vaccine-associated myocarditis, the long-term outcomes of both COVID-19 and MIS-C, and the impact of these various conditions on the heart in children and young adults. In addition, any new antiviral therapies need to be tested in clinical trials focused on children.

“Although much has been learned about how the virus impacts children’s and young adult’s hearts, how to best treat cardiovascular complications, and prevent severe illness, continued clinical research trials are needed to better understand the long-term cardiovascular impacts,” Dr. Jone said. “It is also important to address health disparities that have become more apparent during the pandemic. We must work to ensure all children receive equal access to vaccination and high-quality care.”

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

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.

“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.

“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.

The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.

However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
 

Is there any way to reduce exposure?

PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.

Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.

The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.

While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”

“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.

In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
 

Prospective findings from the SWAN-MPS study

The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.

Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.

Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.

namiroz/iStock/Getty Images

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

Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.

“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.

“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.

The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.

However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
 

Is there any way to reduce exposure?

PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.

Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.

The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.

While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”

“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.

In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
 

Prospective findings from the SWAN-MPS study

The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.

Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.

Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.

namiroz/iStock/Getty Images

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

Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.

“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.

“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.

The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.

However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
 

Is there any way to reduce exposure?

PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.

Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.

The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.

While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”

“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.

In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
 

Prospective findings from the SWAN-MPS study

The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.

Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.

Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.

namiroz/iStock/Getty Images

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

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

A popular fitness tracker company has received approval from the Food and Drug Administration for a new software algorithm to detect atrial fibrillation (AFib), Fitbit announced on April 11.

The algorithm will be the basis of an upcoming Fitbit feature called Irregular Heart Rhythm Notifications, the company said in a press release.

The approval was based on data from the Fitbit Heart Study, which was conducted entirely virtually in more than 455,000 U.S. adults. Participants who had an irregular heart rhythm detected by the software algorithm were notified and invited to meet with a telehealth doctor. They then received a 1-week ECG patch monitor to wear along with the smartwatch or fitness tracker.

Results, presented at the annual scientific sessions of the American Heart Association in November 2021, showed that the positive predictive value of the Fitbit algorithm for detecting undiagnosed AFib with a range of wearable devices was 98%. Notably, irregular heart rhythm detection occurred in 1% of participants overall and 4% of those older than 65 years.

The algorithm works by using an optical measurement method called photoplethysmography (PPG), along with heart rate input from the Fitbit’s photodetector device.

It operates only when the user is still or at rest, so overnight use is important for detection, the company noted.

The upcoming Irregular Heart Rhythm Notifications feature will complement the existing ECG app, providing two ways to detect AFib. The ECG app provides a “spot-check approach” in which the users can screen themselves, and the PPG-based feature will allow for long-term heart rhythm assessment, the statement explained.

“Undiagnosed atrial fibrillation can lead to strokes, and early detection of atrial fibrillation may allow doctors to prescribe medications that are effective at preventing strokes,” said Steven A. Lubitz, MD, MPH, a cardiologist at Harvard University and Massachusetts General Hospital, both in Boston, at the AHA meeting.

A popular fitness tracker company has received approval from the Food and Drug Administration for a new software algorithm to detect atrial fibrillation (AFib), Fitbit announced on April 11.

The algorithm will be the basis of an upcoming Fitbit feature called Irregular Heart Rhythm Notifications, the company said in a press release.

The approval was based on data from the Fitbit Heart Study, which was conducted entirely virtually in more than 455,000 U.S. adults. Participants who had an irregular heart rhythm detected by the software algorithm were notified and invited to meet with a telehealth doctor. They then received a 1-week ECG patch monitor to wear along with the smartwatch or fitness tracker.

Results, presented at the annual scientific sessions of the American Heart Association in November 2021, showed that the positive predictive value of the Fitbit algorithm for detecting undiagnosed AFib with a range of wearable devices was 98%. Notably, irregular heart rhythm detection occurred in 1% of participants overall and 4% of those older than 65 years.

The algorithm works by using an optical measurement method called photoplethysmography (PPG), along with heart rate input from the Fitbit’s photodetector device.

It operates only when the user is still or at rest, so overnight use is important for detection, the company noted.

The upcoming Irregular Heart Rhythm Notifications feature will complement the existing ECG app, providing two ways to detect AFib. The ECG app provides a “spot-check approach” in which the users can screen themselves, and the PPG-based feature will allow for long-term heart rhythm assessment, the statement explained.

“Undiagnosed atrial fibrillation can lead to strokes, and early detection of atrial fibrillation may allow doctors to prescribe medications that are effective at preventing strokes,” said Steven A. Lubitz, MD, MPH, a cardiologist at Harvard University and Massachusetts General Hospital, both in Boston, at the AHA meeting.

A popular fitness tracker company has received approval from the Food and Drug Administration for a new software algorithm to detect atrial fibrillation (AFib), Fitbit announced on April 11.

The algorithm will be the basis of an upcoming Fitbit feature called Irregular Heart Rhythm Notifications, the company said in a press release.

The approval was based on data from the Fitbit Heart Study, which was conducted entirely virtually in more than 455,000 U.S. adults. Participants who had an irregular heart rhythm detected by the software algorithm were notified and invited to meet with a telehealth doctor. They then received a 1-week ECG patch monitor to wear along with the smartwatch or fitness tracker.

Results, presented at the annual scientific sessions of the American Heart Association in November 2021, showed that the positive predictive value of the Fitbit algorithm for detecting undiagnosed AFib with a range of wearable devices was 98%. Notably, irregular heart rhythm detection occurred in 1% of participants overall and 4% of those older than 65 years.

The algorithm works by using an optical measurement method called photoplethysmography (PPG), along with heart rate input from the Fitbit’s photodetector device.

It operates only when the user is still or at rest, so overnight use is important for detection, the company noted.

The upcoming Irregular Heart Rhythm Notifications feature will complement the existing ECG app, providing two ways to detect AFib. The ECG app provides a “spot-check approach” in which the users can screen themselves, and the PPG-based feature will allow for long-term heart rhythm assessment, the statement explained.

“Undiagnosed atrial fibrillation can lead to strokes, and early detection of atrial fibrillation may allow doctors to prescribe medications that are effective at preventing strokes,” said Steven A. Lubitz, MD, MPH, a cardiologist at Harvard University and Massachusetts General Hospital, both in Boston, at the AHA meeting.

Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.

For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.

“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.

In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).

As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.

The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.

In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.

More than 4,000 patients evaluated at 5 years

In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.

SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.

When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.

There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).

In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
 

SVD linked to doubling of mortality

SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).

The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.

Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.

“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.

This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.

Several experts agreed that this is important new information.

“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.

Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.

Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.

“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”

Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.

Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.

For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.

“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.

In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).

As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.

The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.

In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.

More than 4,000 patients evaluated at 5 years

In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.

SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.

When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.

There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).

In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
 

SVD linked to doubling of mortality

SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).

The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.

Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.

“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.

This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.

Several experts agreed that this is important new information.

“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.

Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.

Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.

“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”

Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.

Structural aortic valve deterioration (SVD) at 5 years is lower following repair with a contemporary transcatheter implantation (TAVI) device than with surgery, according to a pooled analysis of major trials.

For healthier patients with a relatively long life expectancy, this is important information for deciding whether to undergo TAVI or surgical aortic valve repair (SAVR), Michael J. Reardon, MD, said at the annual scientific sessions of the American College of Cardiology.

“Every week I get this question about which repair is more durable,” said Dr. Reardon, whose study was not only designed to compare device deterioration but to evaluate the effect of SVD on major outcomes.

In this analysis, the rates of SVD were compared for the self-expanding supra-annular CoreValve Evolut device and SAVR. The SVD curves separated within the first year. At 5 years, the differences were highly significant favoring TAVI (2.57% vs. 4.38%; P = .0095).

As part of this analysis, the impact of SVD was also assessed independent of type of repair. At 5 years, those with SVD relative to those without had an approximately twofold increase in all-cause mortality, cardiovascular mortality, and hospitalization of aortic valve worsening. These risks were elevated regardless of type of valve repair.

The data presented by Dr. Reardon can be considered device specific. The earlier PARTNER 2A study comparing older- and newer-generation TAVI devices with SAVR produced a different result. When a second-generation balloon-expandable SAPIEN XT device and a third-generation SAPIEN 3 device were compared with surgery, neither device achieved lower SVD rates relative to SAVR.

In PARTNER 2A, the SVD rate for the older device was nearly three times greater than SAVR (1.61 vs. 0.58 per 100 patient-years). The numerically higher SVD rates for the newer device (0.68 vs. 0.58 per 100 patient-years) was not statistically different, but the TAVI device was not superior.

More than 4,000 patients evaluated at 5 years

In the analysis presented by Dr. Reardon, data were pooled from the randomized CoreValve U.S. High-Risk Pivotal Trial and the SURTAVI Intermediate Risk Trial. Together, these studies randomized 971 patients to surgery and 1,128 patients to TAVI. Data on an additional 2,663 patients treated with the Evolut valve in two registries were added to the randomized trial data, providing data on 4,762 total patients with 5-year follow-up.

SVD was defined by two criteria. The first was a mean gradient increase of at least 10 mm Hg plus a mean overall gradient of at least 20 mm Hg as measured with echocardiography and assessed, when possible, by an independent core laboratory. The second was new-onset or increased intraprosthetic aortic regurgitation of at least moderate severity.

When graphed over time, the SVD curves separated in favor of TAVI after about 6 months of follow-up. The shape of the curves also differed. Unlike the steady rise in SVD observed in the surgery group, the SVD rate in the TAVI group remained below 1% for almost 4 years before beginning to climb.

There was greater relative benefit for the TAVI device in patients with annular diameters of 23 mm or less. Unlike the rise in SVD rates that began about 6 months after SAVR, the SVD rates in the TAVI patients remained at 0% for more than 2 years. At 5 years, the differences remained significant favoring TAVI (1.39% vs. 5.86%; P = .049).

In those with larger annular diameters, there was still a consistently lower SVD rate over time for TAVI relative to SAVR, but the trend for an advantage at 5 years fell just short of significance (2.48% vs. 3.96%; P = .067).
 

SVD linked to doubling of mortality

SVD worsened outcomes. When all data surgery and TAVI data were pooled, the hazard ratios corresponded with about a doubling of risk for major adverse outcomes, including all-cause mortality (HR, 1.98; P < .001), cardiovascular mortality (HR, 1.82; P = .008), and hospitalization for aortic valve disease or worsening heart failure (HR, 2.11; P = .01). The relative risks were similar in the two treatment groups, including the risk of all-cause mortality (HR, 2.24; P < .001 for TAVI vs. HR, 2.45; P = .002 for SAVR).

The predictors for SVD on multivariate analysis included female sex, increased body surface area, prior percutaneous coronary intervention, and a prior diagnosis of atrial fibrillation.

Design improvements in TAVI devices are likely to explain these results, said Dr. Reardon, chair of cardiovascular research at Houston Methodist Hospital.

“The CoreValve/Evolut supra-annular, self-expanding bioprosthesis is the first and only transcatheter bioprosthesis to demonstrate lower rates of SVD, compared with surgery,” Dr. Reardon said.

This analysis validated the risks posed by the definition of SVD applied in this study, which appears to be a practical tool for tracking valve function and patient risk. Dr. Reardon also said that the study confirms the value of serial Doppler transthoracic echocardiography as a tool for monitoring SVD.

Several experts agreed that this is important new information.

“This is a remarkable series of findings,” said James McClurken, MD, who is a cardiovascular surgeon affiliated with Temple University, Philadelphia, and practices in Doylestown, Penn. By both demonstrating the prognostic importance of SVD and showing differences between the study device and SAVR, this trial will yield practical data to inform patients about relative risks and benefits.

Athena Poppas, MD, the new president of the ACC and a professor of medicine at Brown University, Providence, R.I., called this study “practice changing” for the same reasons. She also thinks it has valuable data for guiding choice of intervention.

Overall, the data are likely to change thinking about the role of TAVI and surgery in younger, fit patients, according to Megan Coylewright, MD, chief of cardiology at Erlanger Cardiology, Chattanooga, Tenn.

“There are patients [in need of aortic valve repair] with a long life expectancy who have been told you have to have a surgical repair because we know they last longer,” she said. Although she said that relative outcomes after longer follow-up remain unknown, “I think this does throw that comment into question.”

Dr. Reardon has financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical. Dr. Poppas and McClurken reported no potential financial conflicts of interest. Dr. Coylewright reported financial relationships with Abbott, Alleviant, Boston Scientific, Cardiosmart, Edwards Lifesciences, Medtronic, and Occlutech. The study received financial support from Medtronic.

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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