Cardiology

An estimated 450,000 US deaths are expected this year from conditions attributed to cigarette smoking. Although the percentage of adults who smoke declined from 21% in 2005 to 11% in 2022, the annual death toll has been stable since 2005 and isn’t expected to decline until 2030, owing to an aging population of current and former smokers.

In 2022, based on a national survey, two thirds of the 28.8 million US adult smokers wanted to quit, and more than half tried quitting on their own or with the help of clinicians, but less than 9% succeeded in kicking the habit. The health benefits of quitting, summarized in a patient education handout from the American Cancer Society, include a lower risk for cancer, diabetes, and cardiovascular disease. Furthermore, the handout states, “quitting smoking can add as much as 10 years to your life, compared to if you continued to smoke.”

For my patients older than age 50 who are lifelong smokers, the qualifier “as much as” can be a sticking point. Although most recognize that continuing to smoke exposes them to greater health risks and are willing to undergo lung cancer screening and receive pneumococcal vaccines, a kind of fatalism frequently sets in. I’ve heard more times than I can recall some version of the declaration, “It’s too late for quitting to make much difference for me.” Many smokers think that once they reach middle age, gains in life expectancy will be too small to be worth the intense effort and multiple failed attempts that are typically required to quit permanently. Until recently, there were few data I could call on to persuade them they were wrong.

In February 2024, Dr. Eo Rin Cho and colleagues pooled data from four national cohort studies (United States, United Kingdom, Norway, and Canada) to calculate mortality differences among current, former, and never smokers aged 20-79 years. Compared with never smokers, lifelong smokers died an average of 12-13 years earlier. However, quitting before age 50 nearly eliminated the excess mortality associated with smoking, and in the 50- to 59-year-old age group, cessation eventually reduced excess mortality by 92%-95%. Better yet, more than half of the benefits occurred within the first 3 years after cessation.

At first glance, these estimates may seem too good to be true. A few months later, though, a different research group, using data from a large cancer prevention study and 2018 US population census and mortality rates, largely confirmed their findings. Dr. Thuy Le and colleagues found that quitting at age 35, 45, 55, 65, or 75 years resulted in average life gains of 8, 5.6, 3.5, 1.7, and 0.7 years, respectively, relative to continuing to smoke. Because no patient is average, the analysis also presented some helpful probabilities. For example, a smoker who quits at age 65 has about a 1 in 4 chance of gaining at least 1 full year of life and a 1 in 6 chance of gaining at least 4 years. In other words, from a life expectancy perspective alone, it’s almost never too late to quit smoking.

Dr. Lin is a family physician and Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor. He has disclosed no relevant financial relationships.

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

An estimated 450,000 US deaths are expected this year from conditions attributed to cigarette smoking. Although the percentage of adults who smoke declined from 21% in 2005 to 11% in 2022, the annual death toll has been stable since 2005 and isn’t expected to decline until 2030, owing to an aging population of current and former smokers.

In 2022, based on a national survey, two thirds of the 28.8 million US adult smokers wanted to quit, and more than half tried quitting on their own or with the help of clinicians, but less than 9% succeeded in kicking the habit. The health benefits of quitting, summarized in a patient education handout from the American Cancer Society, include a lower risk for cancer, diabetes, and cardiovascular disease. Furthermore, the handout states, “quitting smoking can add as much as 10 years to your life, compared to if you continued to smoke.”

For my patients older than age 50 who are lifelong smokers, the qualifier “as much as” can be a sticking point. Although most recognize that continuing to smoke exposes them to greater health risks and are willing to undergo lung cancer screening and receive pneumococcal vaccines, a kind of fatalism frequently sets in. I’ve heard more times than I can recall some version of the declaration, “It’s too late for quitting to make much difference for me.” Many smokers think that once they reach middle age, gains in life expectancy will be too small to be worth the intense effort and multiple failed attempts that are typically required to quit permanently. Until recently, there were few data I could call on to persuade them they were wrong.

In February 2024, Dr. Eo Rin Cho and colleagues pooled data from four national cohort studies (United States, United Kingdom, Norway, and Canada) to calculate mortality differences among current, former, and never smokers aged 20-79 years. Compared with never smokers, lifelong smokers died an average of 12-13 years earlier. However, quitting before age 50 nearly eliminated the excess mortality associated with smoking, and in the 50- to 59-year-old age group, cessation eventually reduced excess mortality by 92%-95%. Better yet, more than half of the benefits occurred within the first 3 years after cessation.

At first glance, these estimates may seem too good to be true. A few months later, though, a different research group, using data from a large cancer prevention study and 2018 US population census and mortality rates, largely confirmed their findings. Dr. Thuy Le and colleagues found that quitting at age 35, 45, 55, 65, or 75 years resulted in average life gains of 8, 5.6, 3.5, 1.7, and 0.7 years, respectively, relative to continuing to smoke. Because no patient is average, the analysis also presented some helpful probabilities. For example, a smoker who quits at age 65 has about a 1 in 4 chance of gaining at least 1 full year of life and a 1 in 6 chance of gaining at least 4 years. In other words, from a life expectancy perspective alone, it’s almost never too late to quit smoking.

Dr. Lin is a family physician and Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor. He has disclosed no relevant financial relationships.

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

An estimated 450,000 US deaths are expected this year from conditions attributed to cigarette smoking. Although the percentage of adults who smoke declined from 21% in 2005 to 11% in 2022, the annual death toll has been stable since 2005 and isn’t expected to decline until 2030, owing to an aging population of current and former smokers.

In 2022, based on a national survey, two thirds of the 28.8 million US adult smokers wanted to quit, and more than half tried quitting on their own or with the help of clinicians, but less than 9% succeeded in kicking the habit. The health benefits of quitting, summarized in a patient education handout from the American Cancer Society, include a lower risk for cancer, diabetes, and cardiovascular disease. Furthermore, the handout states, “quitting smoking can add as much as 10 years to your life, compared to if you continued to smoke.”

For my patients older than age 50 who are lifelong smokers, the qualifier “as much as” can be a sticking point. Although most recognize that continuing to smoke exposes them to greater health risks and are willing to undergo lung cancer screening and receive pneumococcal vaccines, a kind of fatalism frequently sets in. I’ve heard more times than I can recall some version of the declaration, “It’s too late for quitting to make much difference for me.” Many smokers think that once they reach middle age, gains in life expectancy will be too small to be worth the intense effort and multiple failed attempts that are typically required to quit permanently. Until recently, there were few data I could call on to persuade them they were wrong.

In February 2024, Dr. Eo Rin Cho and colleagues pooled data from four national cohort studies (United States, United Kingdom, Norway, and Canada) to calculate mortality differences among current, former, and never smokers aged 20-79 years. Compared with never smokers, lifelong smokers died an average of 12-13 years earlier. However, quitting before age 50 nearly eliminated the excess mortality associated with smoking, and in the 50- to 59-year-old age group, cessation eventually reduced excess mortality by 92%-95%. Better yet, more than half of the benefits occurred within the first 3 years after cessation.

At first glance, these estimates may seem too good to be true. A few months later, though, a different research group, using data from a large cancer prevention study and 2018 US population census and mortality rates, largely confirmed their findings. Dr. Thuy Le and colleagues found that quitting at age 35, 45, 55, 65, or 75 years resulted in average life gains of 8, 5.6, 3.5, 1.7, and 0.7 years, respectively, relative to continuing to smoke. Because no patient is average, the analysis also presented some helpful probabilities. For example, a smoker who quits at age 65 has about a 1 in 4 chance of gaining at least 1 full year of life and a 1 in 6 chance of gaining at least 4 years. In other words, from a life expectancy perspective alone, it’s almost never too late to quit smoking.

Dr. Lin is a family physician and Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor. He has disclosed no relevant financial relationships.

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

In 2016, medical device giant Abbott issued a recall for its MitraClip cardiac device — “a Class I recall, the most serious type,” the FDA said.

“Use of this device may cause serious injuries or death,” an FDA notice about the recall said.

But neither the manufacturer nor the FDA actually recalled the device or suspended its use. They allowed doctors to continue implanting the clips in leaky heart valves in what has become a common procedure.

In a notice, the manufacturer explained, “Abbott is not removing product from commercial distribution.” Rather, Abbott revised instructions for use and required doctors who implant the clips to undergo training.

When it comes to medical devices, recalls can include not only “removals,” in which the device is removed from where it is used or sold, but also “corrections,” which address the problem in the field — for instance, by repairing, adjusting, relabeling, or inspecting a device.

“It’s very oxymoronic,” said Rita Redberg, a cardiologist at the University of California-San Francisco and former editor-in-chief of the journal JAMA Internal Medicine. “A recall makes it sound like it’s recalled. But that is not actually what it means.”

Though the FDA and federal regulations call these actions recalls, they might be described more aptly as “non-recalls.” And they have happened repeatedly in recent years. For instance, in addition to other Abbott devices, products made by Medtronic, Abiomed, and Getinge have had recalls that left them in use.
 

Safeguarding the Public

Recalls that leave what the FDA identifies as potentially dangerous products in the marketplace can raise the question: Do they do enough to protect the public?

There are other ways to handle recalls. In announcements about products as varied as crib bumpers, pool drain covers, bicycle helmets, and coffee mugs, the Consumer Product Safety Commission routinely alerts consumers to stop using recalled products and contact the manufacturers for refunds, repairs, or replacements. The National Highway Traffic Safety Administration regularly advises consumers to bring recalled cars back to the dealer to have them fixed. When the U.S. Department of Agriculture and the FDA announce food recalls, they routinely tell consumers to return or discard the food.

In some cases, a medical device that is the subject of a recall can be kept on the market safely because there is a simple fix, said Sanket Dhruva, a cardiologist and an associate professor at UCSF who has studied FDA oversight of devices. In other cases, recalls that don’t remove devices from the market can provide unwarranted reassurance and leave the public at risk, Dhruva said.

From 2019 through 2023, there were 338 Class I medical device recalls, 164 of which were corrections and 174 of which were removals, FDA spokesperson Amanda Hils said.

Some products undergo recall after recall while they remain on the market. Products in the MitraClip line have been the subject of three rounds of recalls, none of which removed devices from use.

“When deciding whether a recall warrants device removal from the field, the FDA considers the frequency and severity of adverse events, effectiveness of the corrective actions that have been executed, and the benefits and risks of preserving patient access to the device,” FDA spokesperson Audra Harrison said.

Where recalled devices have already been implanted, “removal” doesn’t necessarily mean removing them from patients’ bodies. “When an implanted device has the potential to fail unexpectedly, companies often tell doctors to contact their patients to discuss the risk of removing the device compared to the risk of leaving it in place,” the FDA website says.

The FDA allowed the recalled MitraClip devices to remain in use “because the agency believed that the overall benefits of the device continued to outweigh the risks and the firm’s recall strategy was appropriate and adequate,” Harrison said.

The FDA reviews the recall strategies that manufacturers propose and often provides input to ensure the public will be protected, Hils said. The agency also monitors the effectiveness of recalls and, before terminating them, makes sure the strategy was carried out, Hils said.

Abbott, the maker of MitraClip, said the device has been proven safe and effective “based on more than 20 years of clinical evidence and has profoundly improved the lives of people living with mitral regurgitation,” a condition in which blood flows backward through the heart’s mitral valve. The condition can lead to heart failure and death.

“With MitraClip, we’re addressing the needs of people with MR who often have no other options,” company spokesperson Brent Tippen said.

Speaking of the MitraClip recalls, Redberg said, “So hard to imagine these are effective actions in protecting patients.”

In 2021, for Medtronic’s StealthStation S7 cranial software, the company and the FDA sent a different message.

StealthStation is an elaborate system of screens and other equipment that guides neurosurgeons using instruments in the brain — for instance, to biopsy or cut out tumors. Drawing from CT scans, MRIs, and other imaging, it’s meant to show the location of the surgical instruments.

In connection with a Class I November 2021 recall, the FDA website said potential inaccuracies in a biopsy depth gauge could result in “life-threatening injury (such as hemorrhage, unintended tissue damage, or permanent neurological injury), which could lead to death.”

The FDA website explained what Medtronic was doing about it.

“The recalling firm will provide a warning and instructional placard to be applied to impacted systems,” the website said. “Until a software update is available, ensure you are following the instructions below to prevent the issue from occurring,” it advised doctors.

In a statement to KFF Health News, Medtronic spokesperson Erika Winkels said the safety and well-being of patients is the company’s primary concern, and certain issues “can be safely and effectively remedied with a correction on site.”

Richard Everson, a neurosurgeon and an assistant professor at UCLA, noted that the 2021 recall allowed doctors to continue using unaffected StealthStation features, a benefit for patients and facilities depending on them.

“But, I mean, then you could ask, ‘Well, why don’t they just disable the view [of the brain] that’s bugged?’” Everson said. “Why would they give you the option of looking at an inaccurate one?”

“That’s kind of a strange solution,” he said.

The FDA lists the 2021 recall as still open, explaining “not all products have been corrected or removed.”

That recall was not the last word on problems with StealthStation. Since then, the manufacturer has submitted adverse event reports to the FDA describing trouble in cases involving various versions of StealthStation.

In a September 2022 case, guidance provided by a StealthStation device was allegedly off the mark, a procedure was aborted, and, when the patient awoke, they “had almost no speech for two days,” according to a Medtronic report. In the report, Medtronic said there was “insufficient information to determine the relationship of the software to the reported issue.”

In a February 2024 case, after brain surgery, an MRI found that the operation “missed the tumor” and that other tissue was removed instead, according to a report Medtronic submitted to the FDA. In the report, Medtronic said that when a company representative tested the system, it performed as intended.

In March 2024, Medtronic recalled versions of StealthStation S8 without removing them from hospitals. The company said at the time that it would provide a software update.

“Software updates are available to correct the anomalies identified in the 2021 S7 and 2024 S8 recalls and are actively being deployed,” Medtronic’s Winkels told KFF Health News in a July email. “While the software updates for the 2021 S7 recall are complete in the US, they remain ongoing in some international regions.”

In June 2023, Abiomed issued an urgent medical device correction for its Impella 2.5 intravascular micro axial blood pump, which supports the heart. In patients with a certain type of replacement heart valve, there was a risk of “destruction of the impeller blades,” which could cause “low flow” and “embolization of the fractured impeller material,” an entry on the FDA website said.

“Clinicians are cautioned to position the Impella system carefully in patients,” the FDA website said, among other instructions.

The updated instructions “provide technical guidance to mitigate the risk of rare complications,” Abiomed spokesperson Ryan Carbain said. There were no product removals and no reports of adverse events “related to product design or manufacturing,” Carbain said.

Another set of medical devices, Cardiosave Hybrid and Rescue Intra-Aortic Balloon Pumps made by Getinge of Sweden, have failed persistently, according to FDA records.

The devices — which are placed in the aorta, a major artery, to assist the heart — were the subject of eight Class I recalls from December 2022 to July 2023. All were corrections rather than removals, a KFF Health News analysis found.

In a May 2024 letter to health care providers, the FDA said that, in the previous 12 months, it had received almost 3,000 adverse event reports related to the balloon pumps. It was referring to reports of malfunctions and cases in which the products might have caused or contributed to a death or injury. Of those, 15 reportedly involved serious injury or death, the FDA said.

During the summer of 2023, the FDA noted that “alternative treatments are limited” and said the devices could continue to be used.

But, in May, the FDA changed its stance. The agency advised health care facilities to “transition away from these devices and seek alternatives, if possible.”

“These recommendations are based on our continued concerns” that the manufacturer “has not sufficiently addressed the problems and risks with these recalled devices.”

Getinge sent KFF Health News written answers from Elin Frostehav, the company’s president of Acute Care Therapies.

“There is no question that we would have liked to have solved these issues in full much earlier,” she said.

As a result of the FDA’s May action, the company “immediately paused proactive marketing” of the balloon pumps in the United States, and it is selling them only to customers who have no alternatives, Frostehav said.

“We are working with the agency to finalize remediation and product update solutions,” Frostehav said.
 

‘Known Possible Complications’

Abbott’s MitraClip system includes tiny clips implanted in the heart’s mitral valve and the equipment used to implant them. The apparatus features a steering mechanism with hand controls and a catheter that is threaded through a major vein, typically from an incision in the groin, to place one or more clips in the heart.

Worldwide, more than 200,000 people have been treated with MitraClip, according to an Abbott website.

The 2016 MitraClip recall described cases in which “the user was unable to separate the implantable Clip from the delivery system.”

In a news release at the time, Abbott said it had “received a small number of reports” in which that happened.

Those cases “resulted in surgical interventions to remove the delivery system or replace the mitral valve, and it is expected that any future similar incidents would also require surgery to correct the problem,” the FDA said in a 2016 notice. “There was one patient death in these cases as a result of severe comorbidities following surgery.”

Years later, something similar happened.

In February 2021, a clip was implanted in an 81-year-old patient but the doctor couldn’t separate the clip from the delivery system, according to a report Abbott filed with the FDA. The patient was transferred to surgery, where the delivery system “had to be cut down in order to detach the clip.”

The patient then underwent an operation to replace the mitral valve, and, hours later, the patient was brought back to surgery to address bleeding, the report said.

The patient “coded” the next day and died from an aortic bleed, the report said.

In the report to the FDA, the manufacturer blamed “case-specific circumstances.”

“Cardiac arrest, hemorrhage and death are listed” in the device instructions “as known possible complications associated with mitraclip procedures,” the company said. “There is no indication of a product issue with respect to manufacture, design or labeling.”

The third MitraClip recall, initiated in September 2022, cited an “increase in clip locking malfunctions.”

Most of the reported malfunctions were not associated with adverse outcomes, the FDA said then. Treatment with MitraClip “remains within the anticipated risk levels,” the company told customers.

As with the two earlier recalls, the third advised doctors to follow the device’s instructions. But the 2022 recall identified a contributing factor: the way the device was made.

“Abbott has identified a contributing cause … as a change in the material properties of one of the Clip locking components,” the company said in a 2022 letter to customers.

“Abbott is working on producing new lots with updated manufacturing processing and raw material,” the company wrote. In the same letter, Abbott told doctors that, in the meantime, they could use the devices they had in stock.

Six days later, a clip opened while locked and a patient died, according to a report the manufacturer submitted to the FDA.

“There is no evidence that death was related to the device but it was likely related to the procedure,” Abbott wrote.

Now, almost two years later, the 2022 recall remains open, according to the FDA website, and “not all products have been corrected or removed.”

KFF Health News data editor Holly K. Hacker contributed to this report.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

In 2016, medical device giant Abbott issued a recall for its MitraClip cardiac device — “a Class I recall, the most serious type,” the FDA said.

“Use of this device may cause serious injuries or death,” an FDA notice about the recall said.

But neither the manufacturer nor the FDA actually recalled the device or suspended its use. They allowed doctors to continue implanting the clips in leaky heart valves in what has become a common procedure.

In a notice, the manufacturer explained, “Abbott is not removing product from commercial distribution.” Rather, Abbott revised instructions for use and required doctors who implant the clips to undergo training.

When it comes to medical devices, recalls can include not only “removals,” in which the device is removed from where it is used or sold, but also “corrections,” which address the problem in the field — for instance, by repairing, adjusting, relabeling, or inspecting a device.

“It’s very oxymoronic,” said Rita Redberg, a cardiologist at the University of California-San Francisco and former editor-in-chief of the journal JAMA Internal Medicine. “A recall makes it sound like it’s recalled. But that is not actually what it means.”

Though the FDA and federal regulations call these actions recalls, they might be described more aptly as “non-recalls.” And they have happened repeatedly in recent years. For instance, in addition to other Abbott devices, products made by Medtronic, Abiomed, and Getinge have had recalls that left them in use.
 

Safeguarding the Public

Recalls that leave what the FDA identifies as potentially dangerous products in the marketplace can raise the question: Do they do enough to protect the public?

There are other ways to handle recalls. In announcements about products as varied as crib bumpers, pool drain covers, bicycle helmets, and coffee mugs, the Consumer Product Safety Commission routinely alerts consumers to stop using recalled products and contact the manufacturers for refunds, repairs, or replacements. The National Highway Traffic Safety Administration regularly advises consumers to bring recalled cars back to the dealer to have them fixed. When the U.S. Department of Agriculture and the FDA announce food recalls, they routinely tell consumers to return or discard the food.

In some cases, a medical device that is the subject of a recall can be kept on the market safely because there is a simple fix, said Sanket Dhruva, a cardiologist and an associate professor at UCSF who has studied FDA oversight of devices. In other cases, recalls that don’t remove devices from the market can provide unwarranted reassurance and leave the public at risk, Dhruva said.

From 2019 through 2023, there were 338 Class I medical device recalls, 164 of which were corrections and 174 of which were removals, FDA spokesperson Amanda Hils said.

Some products undergo recall after recall while they remain on the market. Products in the MitraClip line have been the subject of three rounds of recalls, none of which removed devices from use.

“When deciding whether a recall warrants device removal from the field, the FDA considers the frequency and severity of adverse events, effectiveness of the corrective actions that have been executed, and the benefits and risks of preserving patient access to the device,” FDA spokesperson Audra Harrison said.

Where recalled devices have already been implanted, “removal” doesn’t necessarily mean removing them from patients’ bodies. “When an implanted device has the potential to fail unexpectedly, companies often tell doctors to contact their patients to discuss the risk of removing the device compared to the risk of leaving it in place,” the FDA website says.

The FDA allowed the recalled MitraClip devices to remain in use “because the agency believed that the overall benefits of the device continued to outweigh the risks and the firm’s recall strategy was appropriate and adequate,” Harrison said.

The FDA reviews the recall strategies that manufacturers propose and often provides input to ensure the public will be protected, Hils said. The agency also monitors the effectiveness of recalls and, before terminating them, makes sure the strategy was carried out, Hils said.

Abbott, the maker of MitraClip, said the device has been proven safe and effective “based on more than 20 years of clinical evidence and has profoundly improved the lives of people living with mitral regurgitation,” a condition in which blood flows backward through the heart’s mitral valve. The condition can lead to heart failure and death.

“With MitraClip, we’re addressing the needs of people with MR who often have no other options,” company spokesperson Brent Tippen said.

Speaking of the MitraClip recalls, Redberg said, “So hard to imagine these are effective actions in protecting patients.”

In 2021, for Medtronic’s StealthStation S7 cranial software, the company and the FDA sent a different message.

StealthStation is an elaborate system of screens and other equipment that guides neurosurgeons using instruments in the brain — for instance, to biopsy or cut out tumors. Drawing from CT scans, MRIs, and other imaging, it’s meant to show the location of the surgical instruments.

In connection with a Class I November 2021 recall, the FDA website said potential inaccuracies in a biopsy depth gauge could result in “life-threatening injury (such as hemorrhage, unintended tissue damage, or permanent neurological injury), which could lead to death.”

The FDA website explained what Medtronic was doing about it.

“The recalling firm will provide a warning and instructional placard to be applied to impacted systems,” the website said. “Until a software update is available, ensure you are following the instructions below to prevent the issue from occurring,” it advised doctors.

In a statement to KFF Health News, Medtronic spokesperson Erika Winkels said the safety and well-being of patients is the company’s primary concern, and certain issues “can be safely and effectively remedied with a correction on site.”

Richard Everson, a neurosurgeon and an assistant professor at UCLA, noted that the 2021 recall allowed doctors to continue using unaffected StealthStation features, a benefit for patients and facilities depending on them.

“But, I mean, then you could ask, ‘Well, why don’t they just disable the view [of the brain] that’s bugged?’” Everson said. “Why would they give you the option of looking at an inaccurate one?”

“That’s kind of a strange solution,” he said.

The FDA lists the 2021 recall as still open, explaining “not all products have been corrected or removed.”

That recall was not the last word on problems with StealthStation. Since then, the manufacturer has submitted adverse event reports to the FDA describing trouble in cases involving various versions of StealthStation.

In a September 2022 case, guidance provided by a StealthStation device was allegedly off the mark, a procedure was aborted, and, when the patient awoke, they “had almost no speech for two days,” according to a Medtronic report. In the report, Medtronic said there was “insufficient information to determine the relationship of the software to the reported issue.”

In a February 2024 case, after brain surgery, an MRI found that the operation “missed the tumor” and that other tissue was removed instead, according to a report Medtronic submitted to the FDA. In the report, Medtronic said that when a company representative tested the system, it performed as intended.

In March 2024, Medtronic recalled versions of StealthStation S8 without removing them from hospitals. The company said at the time that it would provide a software update.

“Software updates are available to correct the anomalies identified in the 2021 S7 and 2024 S8 recalls and are actively being deployed,” Medtronic’s Winkels told KFF Health News in a July email. “While the software updates for the 2021 S7 recall are complete in the US, they remain ongoing in some international regions.”

In June 2023, Abiomed issued an urgent medical device correction for its Impella 2.5 intravascular micro axial blood pump, which supports the heart. In patients with a certain type of replacement heart valve, there was a risk of “destruction of the impeller blades,” which could cause “low flow” and “embolization of the fractured impeller material,” an entry on the FDA website said.

“Clinicians are cautioned to position the Impella system carefully in patients,” the FDA website said, among other instructions.

The updated instructions “provide technical guidance to mitigate the risk of rare complications,” Abiomed spokesperson Ryan Carbain said. There were no product removals and no reports of adverse events “related to product design or manufacturing,” Carbain said.

Another set of medical devices, Cardiosave Hybrid and Rescue Intra-Aortic Balloon Pumps made by Getinge of Sweden, have failed persistently, according to FDA records.

The devices — which are placed in the aorta, a major artery, to assist the heart — were the subject of eight Class I recalls from December 2022 to July 2023. All were corrections rather than removals, a KFF Health News analysis found.

In a May 2024 letter to health care providers, the FDA said that, in the previous 12 months, it had received almost 3,000 adverse event reports related to the balloon pumps. It was referring to reports of malfunctions and cases in which the products might have caused or contributed to a death or injury. Of those, 15 reportedly involved serious injury or death, the FDA said.

During the summer of 2023, the FDA noted that “alternative treatments are limited” and said the devices could continue to be used.

But, in May, the FDA changed its stance. The agency advised health care facilities to “transition away from these devices and seek alternatives, if possible.”

“These recommendations are based on our continued concerns” that the manufacturer “has not sufficiently addressed the problems and risks with these recalled devices.”

Getinge sent KFF Health News written answers from Elin Frostehav, the company’s president of Acute Care Therapies.

“There is no question that we would have liked to have solved these issues in full much earlier,” she said.

As a result of the FDA’s May action, the company “immediately paused proactive marketing” of the balloon pumps in the United States, and it is selling them only to customers who have no alternatives, Frostehav said.

“We are working with the agency to finalize remediation and product update solutions,” Frostehav said.
 

‘Known Possible Complications’

Abbott’s MitraClip system includes tiny clips implanted in the heart’s mitral valve and the equipment used to implant them. The apparatus features a steering mechanism with hand controls and a catheter that is threaded through a major vein, typically from an incision in the groin, to place one or more clips in the heart.

Worldwide, more than 200,000 people have been treated with MitraClip, according to an Abbott website.

The 2016 MitraClip recall described cases in which “the user was unable to separate the implantable Clip from the delivery system.”

In a news release at the time, Abbott said it had “received a small number of reports” in which that happened.

Those cases “resulted in surgical interventions to remove the delivery system or replace the mitral valve, and it is expected that any future similar incidents would also require surgery to correct the problem,” the FDA said in a 2016 notice. “There was one patient death in these cases as a result of severe comorbidities following surgery.”

Years later, something similar happened.

In February 2021, a clip was implanted in an 81-year-old patient but the doctor couldn’t separate the clip from the delivery system, according to a report Abbott filed with the FDA. The patient was transferred to surgery, where the delivery system “had to be cut down in order to detach the clip.”

The patient then underwent an operation to replace the mitral valve, and, hours later, the patient was brought back to surgery to address bleeding, the report said.

The patient “coded” the next day and died from an aortic bleed, the report said.

In the report to the FDA, the manufacturer blamed “case-specific circumstances.”

“Cardiac arrest, hemorrhage and death are listed” in the device instructions “as known possible complications associated with mitraclip procedures,” the company said. “There is no indication of a product issue with respect to manufacture, design or labeling.”

The third MitraClip recall, initiated in September 2022, cited an “increase in clip locking malfunctions.”

Most of the reported malfunctions were not associated with adverse outcomes, the FDA said then. Treatment with MitraClip “remains within the anticipated risk levels,” the company told customers.

As with the two earlier recalls, the third advised doctors to follow the device’s instructions. But the 2022 recall identified a contributing factor: the way the device was made.

“Abbott has identified a contributing cause … as a change in the material properties of one of the Clip locking components,” the company said in a 2022 letter to customers.

“Abbott is working on producing new lots with updated manufacturing processing and raw material,” the company wrote. In the same letter, Abbott told doctors that, in the meantime, they could use the devices they had in stock.

Six days later, a clip opened while locked and a patient died, according to a report the manufacturer submitted to the FDA.

“There is no evidence that death was related to the device but it was likely related to the procedure,” Abbott wrote.

Now, almost two years later, the 2022 recall remains open, according to the FDA website, and “not all products have been corrected or removed.”

KFF Health News data editor Holly K. Hacker contributed to this report.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

In 2016, medical device giant Abbott issued a recall for its MitraClip cardiac device — “a Class I recall, the most serious type,” the FDA said.

“Use of this device may cause serious injuries or death,” an FDA notice about the recall said.

But neither the manufacturer nor the FDA actually recalled the device or suspended its use. They allowed doctors to continue implanting the clips in leaky heart valves in what has become a common procedure.

In a notice, the manufacturer explained, “Abbott is not removing product from commercial distribution.” Rather, Abbott revised instructions for use and required doctors who implant the clips to undergo training.

When it comes to medical devices, recalls can include not only “removals,” in which the device is removed from where it is used or sold, but also “corrections,” which address the problem in the field — for instance, by repairing, adjusting, relabeling, or inspecting a device.

“It’s very oxymoronic,” said Rita Redberg, a cardiologist at the University of California-San Francisco and former editor-in-chief of the journal JAMA Internal Medicine. “A recall makes it sound like it’s recalled. But that is not actually what it means.”

Though the FDA and federal regulations call these actions recalls, they might be described more aptly as “non-recalls.” And they have happened repeatedly in recent years. For instance, in addition to other Abbott devices, products made by Medtronic, Abiomed, and Getinge have had recalls that left them in use.
 

Safeguarding the Public

Recalls that leave what the FDA identifies as potentially dangerous products in the marketplace can raise the question: Do they do enough to protect the public?

There are other ways to handle recalls. In announcements about products as varied as crib bumpers, pool drain covers, bicycle helmets, and coffee mugs, the Consumer Product Safety Commission routinely alerts consumers to stop using recalled products and contact the manufacturers for refunds, repairs, or replacements. The National Highway Traffic Safety Administration regularly advises consumers to bring recalled cars back to the dealer to have them fixed. When the U.S. Department of Agriculture and the FDA announce food recalls, they routinely tell consumers to return or discard the food.

In some cases, a medical device that is the subject of a recall can be kept on the market safely because there is a simple fix, said Sanket Dhruva, a cardiologist and an associate professor at UCSF who has studied FDA oversight of devices. In other cases, recalls that don’t remove devices from the market can provide unwarranted reassurance and leave the public at risk, Dhruva said.

From 2019 through 2023, there were 338 Class I medical device recalls, 164 of which were corrections and 174 of which were removals, FDA spokesperson Amanda Hils said.

Some products undergo recall after recall while they remain on the market. Products in the MitraClip line have been the subject of three rounds of recalls, none of which removed devices from use.

“When deciding whether a recall warrants device removal from the field, the FDA considers the frequency and severity of adverse events, effectiveness of the corrective actions that have been executed, and the benefits and risks of preserving patient access to the device,” FDA spokesperson Audra Harrison said.

Where recalled devices have already been implanted, “removal” doesn’t necessarily mean removing them from patients’ bodies. “When an implanted device has the potential to fail unexpectedly, companies often tell doctors to contact their patients to discuss the risk of removing the device compared to the risk of leaving it in place,” the FDA website says.

The FDA allowed the recalled MitraClip devices to remain in use “because the agency believed that the overall benefits of the device continued to outweigh the risks and the firm’s recall strategy was appropriate and adequate,” Harrison said.

The FDA reviews the recall strategies that manufacturers propose and often provides input to ensure the public will be protected, Hils said. The agency also monitors the effectiveness of recalls and, before terminating them, makes sure the strategy was carried out, Hils said.

Abbott, the maker of MitraClip, said the device has been proven safe and effective “based on more than 20 years of clinical evidence and has profoundly improved the lives of people living with mitral regurgitation,” a condition in which blood flows backward through the heart’s mitral valve. The condition can lead to heart failure and death.

“With MitraClip, we’re addressing the needs of people with MR who often have no other options,” company spokesperson Brent Tippen said.

Speaking of the MitraClip recalls, Redberg said, “So hard to imagine these are effective actions in protecting patients.”

In 2021, for Medtronic’s StealthStation S7 cranial software, the company and the FDA sent a different message.

StealthStation is an elaborate system of screens and other equipment that guides neurosurgeons using instruments in the brain — for instance, to biopsy or cut out tumors. Drawing from CT scans, MRIs, and other imaging, it’s meant to show the location of the surgical instruments.

In connection with a Class I November 2021 recall, the FDA website said potential inaccuracies in a biopsy depth gauge could result in “life-threatening injury (such as hemorrhage, unintended tissue damage, or permanent neurological injury), which could lead to death.”

The FDA website explained what Medtronic was doing about it.

“The recalling firm will provide a warning and instructional placard to be applied to impacted systems,” the website said. “Until a software update is available, ensure you are following the instructions below to prevent the issue from occurring,” it advised doctors.

In a statement to KFF Health News, Medtronic spokesperson Erika Winkels said the safety and well-being of patients is the company’s primary concern, and certain issues “can be safely and effectively remedied with a correction on site.”

Richard Everson, a neurosurgeon and an assistant professor at UCLA, noted that the 2021 recall allowed doctors to continue using unaffected StealthStation features, a benefit for patients and facilities depending on them.

“But, I mean, then you could ask, ‘Well, why don’t they just disable the view [of the brain] that’s bugged?’” Everson said. “Why would they give you the option of looking at an inaccurate one?”

“That’s kind of a strange solution,” he said.

The FDA lists the 2021 recall as still open, explaining “not all products have been corrected or removed.”

That recall was not the last word on problems with StealthStation. Since then, the manufacturer has submitted adverse event reports to the FDA describing trouble in cases involving various versions of StealthStation.

In a September 2022 case, guidance provided by a StealthStation device was allegedly off the mark, a procedure was aborted, and, when the patient awoke, they “had almost no speech for two days,” according to a Medtronic report. In the report, Medtronic said there was “insufficient information to determine the relationship of the software to the reported issue.”

In a February 2024 case, after brain surgery, an MRI found that the operation “missed the tumor” and that other tissue was removed instead, according to a report Medtronic submitted to the FDA. In the report, Medtronic said that when a company representative tested the system, it performed as intended.

In March 2024, Medtronic recalled versions of StealthStation S8 without removing them from hospitals. The company said at the time that it would provide a software update.

“Software updates are available to correct the anomalies identified in the 2021 S7 and 2024 S8 recalls and are actively being deployed,” Medtronic’s Winkels told KFF Health News in a July email. “While the software updates for the 2021 S7 recall are complete in the US, they remain ongoing in some international regions.”

In June 2023, Abiomed issued an urgent medical device correction for its Impella 2.5 intravascular micro axial blood pump, which supports the heart. In patients with a certain type of replacement heart valve, there was a risk of “destruction of the impeller blades,” which could cause “low flow” and “embolization of the fractured impeller material,” an entry on the FDA website said.

“Clinicians are cautioned to position the Impella system carefully in patients,” the FDA website said, among other instructions.

The updated instructions “provide technical guidance to mitigate the risk of rare complications,” Abiomed spokesperson Ryan Carbain said. There were no product removals and no reports of adverse events “related to product design or manufacturing,” Carbain said.

Another set of medical devices, Cardiosave Hybrid and Rescue Intra-Aortic Balloon Pumps made by Getinge of Sweden, have failed persistently, according to FDA records.

The devices — which are placed in the aorta, a major artery, to assist the heart — were the subject of eight Class I recalls from December 2022 to July 2023. All were corrections rather than removals, a KFF Health News analysis found.

In a May 2024 letter to health care providers, the FDA said that, in the previous 12 months, it had received almost 3,000 adverse event reports related to the balloon pumps. It was referring to reports of malfunctions and cases in which the products might have caused or contributed to a death or injury. Of those, 15 reportedly involved serious injury or death, the FDA said.

During the summer of 2023, the FDA noted that “alternative treatments are limited” and said the devices could continue to be used.

But, in May, the FDA changed its stance. The agency advised health care facilities to “transition away from these devices and seek alternatives, if possible.”

“These recommendations are based on our continued concerns” that the manufacturer “has not sufficiently addressed the problems and risks with these recalled devices.”

Getinge sent KFF Health News written answers from Elin Frostehav, the company’s president of Acute Care Therapies.

“There is no question that we would have liked to have solved these issues in full much earlier,” she said.

As a result of the FDA’s May action, the company “immediately paused proactive marketing” of the balloon pumps in the United States, and it is selling them only to customers who have no alternatives, Frostehav said.

“We are working with the agency to finalize remediation and product update solutions,” Frostehav said.
 

‘Known Possible Complications’

Abbott’s MitraClip system includes tiny clips implanted in the heart’s mitral valve and the equipment used to implant them. The apparatus features a steering mechanism with hand controls and a catheter that is threaded through a major vein, typically from an incision in the groin, to place one or more clips in the heart.

Worldwide, more than 200,000 people have been treated with MitraClip, according to an Abbott website.

The 2016 MitraClip recall described cases in which “the user was unable to separate the implantable Clip from the delivery system.”

In a news release at the time, Abbott said it had “received a small number of reports” in which that happened.

Those cases “resulted in surgical interventions to remove the delivery system or replace the mitral valve, and it is expected that any future similar incidents would also require surgery to correct the problem,” the FDA said in a 2016 notice. “There was one patient death in these cases as a result of severe comorbidities following surgery.”

Years later, something similar happened.

In February 2021, a clip was implanted in an 81-year-old patient but the doctor couldn’t separate the clip from the delivery system, according to a report Abbott filed with the FDA. The patient was transferred to surgery, where the delivery system “had to be cut down in order to detach the clip.”

The patient then underwent an operation to replace the mitral valve, and, hours later, the patient was brought back to surgery to address bleeding, the report said.

The patient “coded” the next day and died from an aortic bleed, the report said.

In the report to the FDA, the manufacturer blamed “case-specific circumstances.”

“Cardiac arrest, hemorrhage and death are listed” in the device instructions “as known possible complications associated with mitraclip procedures,” the company said. “There is no indication of a product issue with respect to manufacture, design or labeling.”

The third MitraClip recall, initiated in September 2022, cited an “increase in clip locking malfunctions.”

Most of the reported malfunctions were not associated with adverse outcomes, the FDA said then. Treatment with MitraClip “remains within the anticipated risk levels,” the company told customers.

As with the two earlier recalls, the third advised doctors to follow the device’s instructions. But the 2022 recall identified a contributing factor: the way the device was made.

“Abbott has identified a contributing cause … as a change in the material properties of one of the Clip locking components,” the company said in a 2022 letter to customers.

“Abbott is working on producing new lots with updated manufacturing processing and raw material,” the company wrote. In the same letter, Abbott told doctors that, in the meantime, they could use the devices they had in stock.

Six days later, a clip opened while locked and a patient died, according to a report the manufacturer submitted to the FDA.

“There is no evidence that death was related to the device but it was likely related to the procedure,” Abbott wrote.

Now, almost two years later, the 2022 recall remains open, according to the FDA website, and “not all products have been corrected or removed.”

KFF Health News data editor Holly K. Hacker contributed to this report.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

At least 25% of unresponsive patients with a disorder of consciousness show signs of brain activity, an estimate that is higher than previous studies suggest.

“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.

“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”

The findings were published online in The New England Journal of Medicine.
 

Clinical Implications? 

Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”

Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.

Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.

In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.

Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.

Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
 

Response to Commands

Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.

To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.

About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.

Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.

Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.

Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.

The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.

Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.

The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear. 

The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
 

Higher Rate of Awareness Than in Previous Research

The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said. 

The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).

Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).

Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.

Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.

Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.

Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”

These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”

All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.

Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.

“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote. 

Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
 

Challenging Research

Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.

“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.” 

Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.

“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.

Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources. 

“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.” 

Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal. 

The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
 

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

At least 25% of unresponsive patients with a disorder of consciousness show signs of brain activity, an estimate that is higher than previous studies suggest.

“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.

“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”

The findings were published online in The New England Journal of Medicine.
 

Clinical Implications? 

Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”

Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.

Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.

In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.

Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.

Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
 

Response to Commands

Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.

To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.

About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.

Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.

Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.

Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.

The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.

Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.

The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear. 

The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
 

Higher Rate of Awareness Than in Previous Research

The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said. 

The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).

Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).

Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.

Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.

Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.

Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”

These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”

All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.

Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.

“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote. 

Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
 

Challenging Research

Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.

“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.” 

Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.

“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.

Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources. 

“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.” 

Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal. 

The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
 

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

At least 25% of unresponsive patients with a disorder of consciousness show signs of brain activity, an estimate that is higher than previous studies suggest.

“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.

“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”

The findings were published online in The New England Journal of Medicine.
 

Clinical Implications? 

Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”

Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.

Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.

In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.

Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.

Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
 

Response to Commands

Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.

To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.

About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.

Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.

Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.

Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.

The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.

Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.

The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear. 

The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
 

Higher Rate of Awareness Than in Previous Research

The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said. 

The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).

Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).

Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.

Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.

Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.

Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”

These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”

All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.

Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.

“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote. 

Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
 

Challenging Research

Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.

“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.” 

Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.

“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.

Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources. 

“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.” 

Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal. 

The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
 

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

• VA Overview
• Dermatology
• Depression and PTSD
• Diabetes
• Cardiology
• Arthritis
• Traumatic Brain Injury (TBI)
• Women's Health
• Substance Use Disorder
• Transgender and Gender-Diverse Care
• Respiratory Health
• Age-Related Macular Degeneration (AMD)
• Parkinson Disease
• Amyotrophic Lateral Sclerosis (ALS)

• VA Overview
• Dermatology
• Depression and PTSD
• Diabetes
• Cardiology
• Arthritis
• Traumatic Brain Injury (TBI)
• Women's Health
• Substance Use Disorder
• Transgender and Gender-Diverse Care
• Respiratory Health
• Age-Related Macular Degeneration (AMD)
• Parkinson Disease
• Amyotrophic Lateral Sclerosis (ALS)

• VA Overview
• Dermatology
• Depression and PTSD
• Diabetes
• Cardiology
• Arthritis
• Traumatic Brain Injury (TBI)
• Women's Health
• Substance Use Disorder
• Transgender and Gender-Diverse Care
• Respiratory Health
• Age-Related Macular Degeneration (AMD)
• Parkinson Disease
• Amyotrophic Lateral Sclerosis (ALS)

Click to view more from Federal Health Care Data Trends 2024.

Click to view more from Federal Health Care Data Trends 2024.

Click to view more from Federal Health Care Data Trends 2024.

TOPLINE:

A higher resting heart rate, even within the normal range, is linked to an increased risk for mortality and cardiovascular events in patients with non–dialysis-dependent chronic kidney disease (CKD).

METHODOLOGY:

• An elevated resting heart rate is an independent risk factor for all-cause mortality and cardiovascular events in the general population; however, the correlation between heart rate and mortality in patients with CKD is unclear.
• Researchers analyzed the longitudinal data of patients with non–dialysis-dependent CKD enrolled in the Fukushima CKD Cohort Study to investigate the association between resting heart rate and adverse clinical outcomes.
• The patient cohort was stratified into four groups on the basis of resting heart rates: < 70, 70-79, 80-89, and ≥ 90 beats/min.
• The primary and secondary outcomes were all-cause mortality and cardiovascular events, respectively, the latter category including myocardial infarction, angina pectoris, and heart failure.

TAKEAWAY:

• Researchers enrolled 1353 patients with non–dialysis-dependent CKD (median age, 65 years; 56.7% men; median estimated glomerular filtration rate, 52.2 mL/min/1.73 m²) who had a median heart rate of 76 beats/min.
• During the median observation period of 4.9 years, 123 patients died and 163 developed cardiovascular events.
• Compared with patients with a resting heart rate < 70 beats/min, those with a resting heart rate of 80-89 and ≥ 90 beats/min had an adjusted hazard ratio of 1.74 and 2.61 for all-cause mortality, respectively.
• Similarly, the risk for cardiovascular events was higher in patients with a heart rate of 80-89 beats/min than in those with a heart rate < 70 beats/min (adjusted hazard ratio, 1.70).

IN PRACTICE:

“The present study supported the idea that reducing heart rate might be effective for CKD patients with a heart rate ≥ 70/min, since the lowest risk of mortality was seen in patients with heart rate < 70/min,” the authors concluded. 

SOURCE:

This study was led by Hirotaka Saito, Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima City, Japan. It was published online in Scientific Reports.

LIMITATIONS:

Heart rate was measured using a standard sphygmomanometer or an automated device, rather than an electrocardiograph, which may have introduced measurement variability. The observational nature of the study precluded the establishment of cause-and-effect relationships between heart rate and clinical outcomes. Additionally, variables such as lifestyle factors, underlying health conditions, and socioeconomic factors were not measured, which could have affected the results. 

DISCLOSURES:

Some authors received research funding from Chugai Pharmaceutical, Kowa Pharmaceutical, Ono Pharmaceutical, and other sources. They declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A higher resting heart rate, even within the normal range, is linked to an increased risk for mortality and cardiovascular events in patients with non–dialysis-dependent chronic kidney disease (CKD).

METHODOLOGY:

• An elevated resting heart rate is an independent risk factor for all-cause mortality and cardiovascular events in the general population; however, the correlation between heart rate and mortality in patients with CKD is unclear.
• Researchers analyzed the longitudinal data of patients with non–dialysis-dependent CKD enrolled in the Fukushima CKD Cohort Study to investigate the association between resting heart rate and adverse clinical outcomes.
• The patient cohort was stratified into four groups on the basis of resting heart rates: < 70, 70-79, 80-89, and ≥ 90 beats/min.
• The primary and secondary outcomes were all-cause mortality and cardiovascular events, respectively, the latter category including myocardial infarction, angina pectoris, and heart failure.

TAKEAWAY:

• Researchers enrolled 1353 patients with non–dialysis-dependent CKD (median age, 65 years; 56.7% men; median estimated glomerular filtration rate, 52.2 mL/min/1.73 m²) who had a median heart rate of 76 beats/min.
• During the median observation period of 4.9 years, 123 patients died and 163 developed cardiovascular events.
• Compared with patients with a resting heart rate < 70 beats/min, those with a resting heart rate of 80-89 and ≥ 90 beats/min had an adjusted hazard ratio of 1.74 and 2.61 for all-cause mortality, respectively.
• Similarly, the risk for cardiovascular events was higher in patients with a heart rate of 80-89 beats/min than in those with a heart rate < 70 beats/min (adjusted hazard ratio, 1.70).

IN PRACTICE:

“The present study supported the idea that reducing heart rate might be effective for CKD patients with a heart rate ≥ 70/min, since the lowest risk of mortality was seen in patients with heart rate < 70/min,” the authors concluded. 

SOURCE:

This study was led by Hirotaka Saito, Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima City, Japan. It was published online in Scientific Reports.

LIMITATIONS:

Heart rate was measured using a standard sphygmomanometer or an automated device, rather than an electrocardiograph, which may have introduced measurement variability. The observational nature of the study precluded the establishment of cause-and-effect relationships between heart rate and clinical outcomes. Additionally, variables such as lifestyle factors, underlying health conditions, and socioeconomic factors were not measured, which could have affected the results. 

DISCLOSURES:

Some authors received research funding from Chugai Pharmaceutical, Kowa Pharmaceutical, Ono Pharmaceutical, and other sources. They declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A higher resting heart rate, even within the normal range, is linked to an increased risk for mortality and cardiovascular events in patients with non–dialysis-dependent chronic kidney disease (CKD).

METHODOLOGY:

• An elevated resting heart rate is an independent risk factor for all-cause mortality and cardiovascular events in the general population; however, the correlation between heart rate and mortality in patients with CKD is unclear.
• Researchers analyzed the longitudinal data of patients with non–dialysis-dependent CKD enrolled in the Fukushima CKD Cohort Study to investigate the association between resting heart rate and adverse clinical outcomes.
• The patient cohort was stratified into four groups on the basis of resting heart rates: < 70, 70-79, 80-89, and ≥ 90 beats/min.
• The primary and secondary outcomes were all-cause mortality and cardiovascular events, respectively, the latter category including myocardial infarction, angina pectoris, and heart failure.

TAKEAWAY:

• Researchers enrolled 1353 patients with non–dialysis-dependent CKD (median age, 65 years; 56.7% men; median estimated glomerular filtration rate, 52.2 mL/min/1.73 m²) who had a median heart rate of 76 beats/min.
• During the median observation period of 4.9 years, 123 patients died and 163 developed cardiovascular events.
• Compared with patients with a resting heart rate < 70 beats/min, those with a resting heart rate of 80-89 and ≥ 90 beats/min had an adjusted hazard ratio of 1.74 and 2.61 for all-cause mortality, respectively.
• Similarly, the risk for cardiovascular events was higher in patients with a heart rate of 80-89 beats/min than in those with a heart rate < 70 beats/min (adjusted hazard ratio, 1.70).

IN PRACTICE:

“The present study supported the idea that reducing heart rate might be effective for CKD patients with a heart rate ≥ 70/min, since the lowest risk of mortality was seen in patients with heart rate < 70/min,” the authors concluded. 

SOURCE:

This study was led by Hirotaka Saito, Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima City, Japan. It was published online in Scientific Reports.

LIMITATIONS:

Heart rate was measured using a standard sphygmomanometer or an automated device, rather than an electrocardiograph, which may have introduced measurement variability. The observational nature of the study precluded the establishment of cause-and-effect relationships between heart rate and clinical outcomes. Additionally, variables such as lifestyle factors, underlying health conditions, and socioeconomic factors were not measured, which could have affected the results. 

DISCLOSURES:

Some authors received research funding from Chugai Pharmaceutical, Kowa Pharmaceutical, Ono Pharmaceutical, and other sources. They declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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