MDedge Cardiology

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

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

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

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

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

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

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

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

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

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

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

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

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

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

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

Vascular damage

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

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

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

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

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

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

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

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

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

New guidance for patients

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

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

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

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

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

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

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

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

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

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

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

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

Vascular damage

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

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

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

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

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

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

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

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

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

New guidance for patients

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

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

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

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

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

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

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

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

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

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

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

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

Vascular damage

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

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

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

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

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

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

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

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

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

New guidance for patients

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Is there any way to reduce exposure?

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

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

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

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

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

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

Prospective findings from the SWAN-MPS study

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

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

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

namiroz/iStock/Getty Images

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

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

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

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

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

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

Is there any way to reduce exposure?

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

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

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

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

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

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

Prospective findings from the SWAN-MPS study

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

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

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

namiroz/iStock/Getty Images

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

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

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

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

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

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

Is there any way to reduce exposure?

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

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

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

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

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

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

Prospective findings from the SWAN-MPS study

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

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

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

namiroz/iStock/Getty Images

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Increasing incidence among women

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

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

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

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

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

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

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

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

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

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

Sex differences in drug responses

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Increasing incidence among women

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

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

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

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

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

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

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

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

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

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

Sex differences in drug responses

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Increasing incidence among women

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

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

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

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

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

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

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

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

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

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

Sex differences in drug responses

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

More than 4,000 patients evaluated at 5 years

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

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

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

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

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

SVD linked to doubling of mortality

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

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

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

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

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

Several experts agreed that this is important new information.

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

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

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

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

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

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

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

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

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

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

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

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

More than 4,000 patients evaluated at 5 years

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

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

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

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

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

SVD linked to doubling of mortality

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

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

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

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

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

Several experts agreed that this is important new information.

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

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

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

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

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

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

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

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

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

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

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

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

More than 4,000 patients evaluated at 5 years

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

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

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

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

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

SVD linked to doubling of mortality

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

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

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

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

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

Several experts agreed that this is important new information.

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

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

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

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

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

Sham-controlled evidence

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

Sham-controlled evidence

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

Sham-controlled evidence

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

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

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

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

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

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

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

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

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

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

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

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

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

Though overall COVID-19 case counts continue to drop nationally, that’s not the story in every U.S. state.

About half the states have reported increases in COVID cases fueled by the Omicron subvariant, Axios reported. Alaska, Vermont, and Rhode Island had the highest increases, with more than 20 new cases per 100,000 people.

Nationally, the statistics are encouraging, with the 7-day average of daily cases around 26,000 on April 6, down from around 41,000 on March 6, according to the Centers for Disease Control and Prevention. The number of deaths has dropped to an average of around 600 a day, down 34% from 2 weeks ago.

National health officials have said some spots would have a lot of COVID cases.

“Looking across the country, we see that 95% of counties are reporting low COVID-19 community levels, which represent over 97% of the U.S. population,” CDC Director Rochelle Walensky, MD, said April 5 at a White House news briefing.

“If we look more closely at the local level, we find a handful of counties where we are seeing increases in both cases and markers of more severe disease, like hospitalizations and in-patient bed capacity, which have resulted in an increased COVID-19 community level in some areas.”

Meanwhile, the Commonwealth Fund issued a report April 8 saying the U.S. vaccine program had prevented an estimated 2.2 million deaths and 17 million hospitalizations.

If the vaccine program didn’t exist, the United States would have had another 66 million COVID infections and spent about $900 billion more on health care, the foundation said.

The United States has reported about 982,000 COVID-related deaths so far with about 80 million COVID cases, according to the CDC.

“Our findings highlight the profound and ongoing impact of the vaccination program in reducing infections, hospitalizations, and deaths,” the Commonwealth Fund said.

“Investing in vaccination programs also has produced substantial cost savings – approximately the size of one-fifth of annual national health expenditures – by dramatically reducing the amount spent on COVID-19 hospitalizations.”

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

Though overall COVID-19 case counts continue to drop nationally, that’s not the story in every U.S. state.

About half the states have reported increases in COVID cases fueled by the Omicron subvariant, Axios reported. Alaska, Vermont, and Rhode Island had the highest increases, with more than 20 new cases per 100,000 people.

Nationally, the statistics are encouraging, with the 7-day average of daily cases around 26,000 on April 6, down from around 41,000 on March 6, according to the Centers for Disease Control and Prevention. The number of deaths has dropped to an average of around 600 a day, down 34% from 2 weeks ago.

National health officials have said some spots would have a lot of COVID cases.

“Looking across the country, we see that 95% of counties are reporting low COVID-19 community levels, which represent over 97% of the U.S. population,” CDC Director Rochelle Walensky, MD, said April 5 at a White House news briefing.

“If we look more closely at the local level, we find a handful of counties where we are seeing increases in both cases and markers of more severe disease, like hospitalizations and in-patient bed capacity, which have resulted in an increased COVID-19 community level in some areas.”

Meanwhile, the Commonwealth Fund issued a report April 8 saying the U.S. vaccine program had prevented an estimated 2.2 million deaths and 17 million hospitalizations.

If the vaccine program didn’t exist, the United States would have had another 66 million COVID infections and spent about $900 billion more on health care, the foundation said.

The United States has reported about 982,000 COVID-related deaths so far with about 80 million COVID cases, according to the CDC.

“Our findings highlight the profound and ongoing impact of the vaccination program in reducing infections, hospitalizations, and deaths,” the Commonwealth Fund said.

“Investing in vaccination programs also has produced substantial cost savings – approximately the size of one-fifth of annual national health expenditures – by dramatically reducing the amount spent on COVID-19 hospitalizations.”

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

Though overall COVID-19 case counts continue to drop nationally, that’s not the story in every U.S. state.

About half the states have reported increases in COVID cases fueled by the Omicron subvariant, Axios reported. Alaska, Vermont, and Rhode Island had the highest increases, with more than 20 new cases per 100,000 people.

Nationally, the statistics are encouraging, with the 7-day average of daily cases around 26,000 on April 6, down from around 41,000 on March 6, according to the Centers for Disease Control and Prevention. The number of deaths has dropped to an average of around 600 a day, down 34% from 2 weeks ago.

National health officials have said some spots would have a lot of COVID cases.

“Looking across the country, we see that 95% of counties are reporting low COVID-19 community levels, which represent over 97% of the U.S. population,” CDC Director Rochelle Walensky, MD, said April 5 at a White House news briefing.

“If we look more closely at the local level, we find a handful of counties where we are seeing increases in both cases and markers of more severe disease, like hospitalizations and in-patient bed capacity, which have resulted in an increased COVID-19 community level in some areas.”

Meanwhile, the Commonwealth Fund issued a report April 8 saying the U.S. vaccine program had prevented an estimated 2.2 million deaths and 17 million hospitalizations.

If the vaccine program didn’t exist, the United States would have had another 66 million COVID infections and spent about $900 billion more on health care, the foundation said.

The United States has reported about 982,000 COVID-related deaths so far with about 80 million COVID cases, according to the CDC.

“Our findings highlight the profound and ongoing impact of the vaccination program in reducing infections, hospitalizations, and deaths,” the Commonwealth Fund said.

“Investing in vaccination programs also has produced substantial cost savings – approximately the size of one-fifth of annual national health expenditures – by dramatically reducing the amount spent on COVID-19 hospitalizations.”

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

Physically fit children have a greater ability to concentrate and better health-related quality of life (HRQOL), according to a new study.

The findings of the German study involving more than 6,500 kids emphasize the importance of cardiorespiratory health in childhood, and support physical fitness initiatives in schools, according to lead author Katharina Köble, MSc, of the Technical University of Munich (Germany), and colleagues.

“Recent studies show that only a few children meet the recommendations of physical activity,” the investigators wrote in Journal of Clinical Medicine.

While the health benefits of physical activity are clearly documented, Ms. Köble and colleagues noted that typical measures of activity, such as accelerometers or self-reported questionnaires, are suboptimal research tools.

“Physical fitness is a more objective parameter to quantify when evaluating health promotion,” the investigators wrote. “Furthermore, cardiorespiratory fitness as part of physical fitness is more strongly related to risk factors of cardiovascular disease than physical activity.”

According to the investigators, physical fitness has also been linked with better concentration and HRQOL, but never in the same population of children.

The new study aimed to address this knowledge gap by assessing 6,533 healthy children aged 6-10 years, approximately half boys and half girls. Associations between physical fitness, concentration, and HRQOL were evaluated using multiple linear regression analysis in participants aged 9-10 years.

Physical fitness was measured using a series of challenges, including curl-ups (pull-ups with palms facing body), push-ups, standing long jump, handgrip strength measurement, and Progressive Aerobic Cardiovascular Endurance Run (PACER). Performing the multistage shuttle run, PACER, “requires participants to maintain the pace set by an audio signal, which progressively increases the intensity every minute.” Results of the PACER test were used to estimate VO_2max.

Concentration was measured using the d2-R test, “a paper-pencil cancellation test, where subjects have to cross out all ‘d’ letters with two dashes under a time limit.”

HRQOL was evaluated with the KINDL questionnaire, which covers emotional well-being, physical well-being, everyday functioning (school), friends, family, and self-esteem.

Analysis showed that physical fitness improved with age (P < .001), except for VO_2max in girls (P = .129). Concentration also improved with age (P < .001), while HRQOL did not (P = .179).

Among children aged 9-10 years, VO_2max scores were strongly associated with both HRQOL (P < .001) and concentration (P < .001).

“VO_2max was found to be one of the main factors influencing concentration levels and HRQOL dimensions in primary school children,” the investigators wrote. “Physical fitness, especially cardiorespiratory performance, should therefore be promoted more specifically in school settings to support the promotion of an overall healthy lifestyle in children and adolescents.”
 

Findings are having a real-word impact, according to researcher

In an interview, Ms. Köble noted that the findings are already having a real-world impact.

“We continued data assessment in the long-term and specifically adapted prevention programs in school to the needs of the school children we identified in our study,” she said. “Schools are partially offering specific movement and nutrition classes now.”

In addition, Ms. Köble and colleagues plan on educating teachers about the “urgent need for sufficient physical activity.”

“Academic performance should be considered as an additional health factor in future studies, as well as screen time and eating patterns, as all those variables showed interactions with physical fitness and concentration. In a subanalysis, we showed that children with better physical fitness and concentration values were those who usually went to higher education secondary schools,” they wrote.
 

VO_2max did not correlate with BMI

Gregory Weaver, MD, a pediatrician at Cleveland Clinic Children’s, voiced some concerns about the reliability of the findings. He noted that VO_2max did not correlate with body mass index or other measures of physical fitness, and that using the PACER test to estimate VO_2max may have skewed the association between physical fitness and concentration.

“It is quite conceivable that children who can maintain the focus to perform maximally on this test will also do well on other tests of attention/concentration,” Dr. Weaver said. “Most children I know would have a very difficult time performing a physical fitness test which requires them to match a recorded pace that slowly increases overtime. I’m not an expert in the area, but it is my understanding that usually VO_2max tests involve a treadmill which allows investigators to have complete control over pace.”

Dr. Weaver concluded that more work is needed to determine if physical fitness interventions can have a positive impact on HRQOL and concentration.

“I think the authors of this study attempted to ask an important question about the possible association between physical fitness and concentration among school aged children,” Dr. Weaver said in an interview. “But what is even more vital are studies demonstrating that a change in modifiable health factors like nutrition, physical fitness, or the built environment can improve quality of life. I was hoping the authors would show that an improvement in VO_2max over time resulted in an improvement in concentration. Frustratingly, that is not what this article demonstrates.”

The investigators and Dr. Weaver reported no conflicts of interest.

Physically fit children have a greater ability to concentrate and better health-related quality of life (HRQOL), according to a new study.

The findings of the German study involving more than 6,500 kids emphasize the importance of cardiorespiratory health in childhood, and support physical fitness initiatives in schools, according to lead author Katharina Köble, MSc, of the Technical University of Munich (Germany), and colleagues.

“Recent studies show that only a few children meet the recommendations of physical activity,” the investigators wrote in Journal of Clinical Medicine.

While the health benefits of physical activity are clearly documented, Ms. Köble and colleagues noted that typical measures of activity, such as accelerometers or self-reported questionnaires, are suboptimal research tools.

“Physical fitness is a more objective parameter to quantify when evaluating health promotion,” the investigators wrote. “Furthermore, cardiorespiratory fitness as part of physical fitness is more strongly related to risk factors of cardiovascular disease than physical activity.”

According to the investigators, physical fitness has also been linked with better concentration and HRQOL, but never in the same population of children.

The new study aimed to address this knowledge gap by assessing 6,533 healthy children aged 6-10 years, approximately half boys and half girls. Associations between physical fitness, concentration, and HRQOL were evaluated using multiple linear regression analysis in participants aged 9-10 years.

Physical fitness was measured using a series of challenges, including curl-ups (pull-ups with palms facing body), push-ups, standing long jump, handgrip strength measurement, and Progressive Aerobic Cardiovascular Endurance Run (PACER). Performing the multistage shuttle run, PACER, “requires participants to maintain the pace set by an audio signal, which progressively increases the intensity every minute.” Results of the PACER test were used to estimate VO_2max.

Concentration was measured using the d2-R test, “a paper-pencil cancellation test, where subjects have to cross out all ‘d’ letters with two dashes under a time limit.”

HRQOL was evaluated with the KINDL questionnaire, which covers emotional well-being, physical well-being, everyday functioning (school), friends, family, and self-esteem.

Analysis showed that physical fitness improved with age (P < .001), except for VO_2max in girls (P = .129). Concentration also improved with age (P < .001), while HRQOL did not (P = .179).

Among children aged 9-10 years, VO_2max scores were strongly associated with both HRQOL (P < .001) and concentration (P < .001).

“VO_2max was found to be one of the main factors influencing concentration levels and HRQOL dimensions in primary school children,” the investigators wrote. “Physical fitness, especially cardiorespiratory performance, should therefore be promoted more specifically in school settings to support the promotion of an overall healthy lifestyle in children and adolescents.”
 

Findings are having a real-word impact, according to researcher

In an interview, Ms. Köble noted that the findings are already having a real-world impact.

“We continued data assessment in the long-term and specifically adapted prevention programs in school to the needs of the school children we identified in our study,” she said. “Schools are partially offering specific movement and nutrition classes now.”

In addition, Ms. Köble and colleagues plan on educating teachers about the “urgent need for sufficient physical activity.”

“Academic performance should be considered as an additional health factor in future studies, as well as screen time and eating patterns, as all those variables showed interactions with physical fitness and concentration. In a subanalysis, we showed that children with better physical fitness and concentration values were those who usually went to higher education secondary schools,” they wrote.
 

VO_2max did not correlate with BMI

Gregory Weaver, MD, a pediatrician at Cleveland Clinic Children’s, voiced some concerns about the reliability of the findings. He noted that VO_2max did not correlate with body mass index or other measures of physical fitness, and that using the PACER test to estimate VO_2max may have skewed the association between physical fitness and concentration.

“It is quite conceivable that children who can maintain the focus to perform maximally on this test will also do well on other tests of attention/concentration,” Dr. Weaver said. “Most children I know would have a very difficult time performing a physical fitness test which requires them to match a recorded pace that slowly increases overtime. I’m not an expert in the area, but it is my understanding that usually VO_2max tests involve a treadmill which allows investigators to have complete control over pace.”

Dr. Weaver concluded that more work is needed to determine if physical fitness interventions can have a positive impact on HRQOL and concentration.

“I think the authors of this study attempted to ask an important question about the possible association between physical fitness and concentration among school aged children,” Dr. Weaver said in an interview. “But what is even more vital are studies demonstrating that a change in modifiable health factors like nutrition, physical fitness, or the built environment can improve quality of life. I was hoping the authors would show that an improvement in VO_2max over time resulted in an improvement in concentration. Frustratingly, that is not what this article demonstrates.”

The investigators and Dr. Weaver reported no conflicts of interest.

Physically fit children have a greater ability to concentrate and better health-related quality of life (HRQOL), according to a new study.

The findings of the German study involving more than 6,500 kids emphasize the importance of cardiorespiratory health in childhood, and support physical fitness initiatives in schools, according to lead author Katharina Köble, MSc, of the Technical University of Munich (Germany), and colleagues.

“Recent studies show that only a few children meet the recommendations of physical activity,” the investigators wrote in Journal of Clinical Medicine.

While the health benefits of physical activity are clearly documented, Ms. Köble and colleagues noted that typical measures of activity, such as accelerometers or self-reported questionnaires, are suboptimal research tools.

“Physical fitness is a more objective parameter to quantify when evaluating health promotion,” the investigators wrote. “Furthermore, cardiorespiratory fitness as part of physical fitness is more strongly related to risk factors of cardiovascular disease than physical activity.”

According to the investigators, physical fitness has also been linked with better concentration and HRQOL, but never in the same population of children.

The new study aimed to address this knowledge gap by assessing 6,533 healthy children aged 6-10 years, approximately half boys and half girls. Associations between physical fitness, concentration, and HRQOL were evaluated using multiple linear regression analysis in participants aged 9-10 years.

Physical fitness was measured using a series of challenges, including curl-ups (pull-ups with palms facing body), push-ups, standing long jump, handgrip strength measurement, and Progressive Aerobic Cardiovascular Endurance Run (PACER). Performing the multistage shuttle run, PACER, “requires participants to maintain the pace set by an audio signal, which progressively increases the intensity every minute.” Results of the PACER test were used to estimate VO_2max.

Concentration was measured using the d2-R test, “a paper-pencil cancellation test, where subjects have to cross out all ‘d’ letters with two dashes under a time limit.”

HRQOL was evaluated with the KINDL questionnaire, which covers emotional well-being, physical well-being, everyday functioning (school), friends, family, and self-esteem.

Analysis showed that physical fitness improved with age (P < .001), except for VO_2max in girls (P = .129). Concentration also improved with age (P < .001), while HRQOL did not (P = .179).

Among children aged 9-10 years, VO_2max scores were strongly associated with both HRQOL (P < .001) and concentration (P < .001).

“VO_2max was found to be one of the main factors influencing concentration levels and HRQOL dimensions in primary school children,” the investigators wrote. “Physical fitness, especially cardiorespiratory performance, should therefore be promoted more specifically in school settings to support the promotion of an overall healthy lifestyle in children and adolescents.”
 

Findings are having a real-word impact, according to researcher

In an interview, Ms. Köble noted that the findings are already having a real-world impact.

“We continued data assessment in the long-term and specifically adapted prevention programs in school to the needs of the school children we identified in our study,” she said. “Schools are partially offering specific movement and nutrition classes now.”

In addition, Ms. Köble and colleagues plan on educating teachers about the “urgent need for sufficient physical activity.”

“Academic performance should be considered as an additional health factor in future studies, as well as screen time and eating patterns, as all those variables showed interactions with physical fitness and concentration. In a subanalysis, we showed that children with better physical fitness and concentration values were those who usually went to higher education secondary schools,” they wrote.
 

VO_2max did not correlate with BMI

Gregory Weaver, MD, a pediatrician at Cleveland Clinic Children’s, voiced some concerns about the reliability of the findings. He noted that VO_2max did not correlate with body mass index or other measures of physical fitness, and that using the PACER test to estimate VO_2max may have skewed the association between physical fitness and concentration.

“It is quite conceivable that children who can maintain the focus to perform maximally on this test will also do well on other tests of attention/concentration,” Dr. Weaver said. “Most children I know would have a very difficult time performing a physical fitness test which requires them to match a recorded pace that slowly increases overtime. I’m not an expert in the area, but it is my understanding that usually VO_2max tests involve a treadmill which allows investigators to have complete control over pace.”

Dr. Weaver concluded that more work is needed to determine if physical fitness interventions can have a positive impact on HRQOL and concentration.

“I think the authors of this study attempted to ask an important question about the possible association between physical fitness and concentration among school aged children,” Dr. Weaver said in an interview. “But what is even more vital are studies demonstrating that a change in modifiable health factors like nutrition, physical fitness, or the built environment can improve quality of life. I was hoping the authors would show that an improvement in VO_2max over time resulted in an improvement in concentration. Frustratingly, that is not what this article demonstrates.”

The investigators and Dr. Weaver reported no conflicts of interest.

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

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

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

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

In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.

Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.

“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”

The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.

“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”

Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”

“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”

For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.

Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”

The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”

Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.

Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”

The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.

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

Several of the core medications for patients with heart failure with reduced ejection fraction (HFrEF) come with a well-known risk of causing hyperkalemia, to which many clinicians respond by pulling back on dosing or withdrawing the culprit drug.

But accompanying renin-angiotensin system–inhibiting agents with the potassium-sequestrant patiromer (Veltassa, Vifor Pharma) appears to shield patients against hyperkalemia enough that they can take more RASI medications at higher doses, suggests a randomized, a controlled study.

Catherine Hackett/MDedge News

The DIAMOND trial’s HFrEF patients, who had current or a history of RASI-related hyperkalemia, added either patiromer or placebo to their guideline-directed medical therapy (GDMT), which includes, even emphasizes, the culprit medication. They include ACE inhibitors, angiotensin-receptor blockers (ARBs), angiotensin-receptor/neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs).

Those taking patiromer tolerated more intense RASI therapy – including MRAs, which are especially prone to causing hyperkalemia – than the patients assigned to placebo. They also maintained lower potassium concentrations and experienced fewer clinically important hyperkalemia episodes, reported Javed Butler, MD, MPH, MBA, Baylor Scott and White Research Institute, Dallas, at the annual scientific sessions of the American College of Cardiology.

The apparent benefit from patiromer came in part from an advantage for a composite hyperkalemia-event endpoint that included mortality, Dr. Butler noted. That advantage seemed to hold regardless of age, sex, body mass index, HFrEF symptom severity, or initial natriuretic peptide levels.

Patients who took patiromer, compared with those who took placebo, showed a 37% reduction in risk for hyperkalemia (P = .006), defined as potassium levels exceeding 5.5 mEq/L, over a median follow-up of 27 weeks. They were 38% less likely to have their MRA dosage reduced to below target level (P = .006).

More patients in the patiromer group than in the control group attained at least 50% of target dosage for MRAs and ACE inhibitors, ARBs, or ARNIs (92% vs. 87%; P = .015).

Patients with HFrEF are unlikely to achieve best possible outcomes without GDMT optimization, but failure to optimize is often attributed to hyperkalemia concerns. DIAMOND, Dr. Butler said, suggests that, by adding the potassium sequestrant to GDMT, “you can simultaneously control potassium and optimize RASI therapy.” Many clinicians seem to believe they can achieve only one or the other.

DIAMOND was too underpowered to show whether preventing hyperkalemia with patiromer could improve clinical outcomes. But failure to optimize RASI medication in HFrEF can worsen risk for heart failure events and death. So “it stands to reason that optimization of RASI therapy without a concomitant risk of hyperkalemia may, in the long run, lead to better outcomes for these patients,” Dr. Butler said in an interview.

Given the drug’s ability to keep potassium levels in check during RASI therapy, Dr. Butler said, “hypokalemia should not be a reason for suboptimal therapy.”

Patiromer and other potassium sequestrants have been available in the United States and Europe for 4-6 years, but their value as adjuncts to RASI medication in HFrEF or other heart failure has been unclear.

Courtesy Massachusetts General Hospital

“There’s a good opportunity to expand the use of the drug. The question is, in whom and when?” James L. Januzzi, MD, Massachusetts General Hospital, Boston, said in an interview.

Some HFrEF patients on GDMT “should be treated with patiromer. The bigger question is, should we give someone who has a history of hyperkalemia another chance at GDMT before we treat them with patiromer? Because they may not necessarily develop hyperkalemia a second time,” said Dr. Januzzi, who was on the DIAMOND endpoint-adjudication committee.

Among the most notable findings of the trial, he said, is that the number of people who developed hyperkalemia on RASI medication, although significantly elevated, “wasn’t as high as they expected it would be,” he said. “The data from DIAMOND argue that if a really significant majority does not become hyperkalemic on rechallenge, jumping straight to a potassium-binding drug may be premature.”

Physicians across specialties can differ in how they interpret potassium-level elevation and can use various cut points to flag when to stop RASI medication or at least hold back on up-titration, Dr. Butler observed. “Cardiologists have a different threshold of potassium that they tolerate than say, for instance, a nephrologist.”

Useful, then, might be a way to tell which patients are most likely to develop hyperkalemia with RASI up-titration and so might benefit from a potassium-binding agent right away. But DIAMOND, Dr. Butler said, “does not necessarily define any patient phenotype or any potassium level where we would say that you should use a potassium binder.”

The trial entered 1,642 patients with HFrEF and current or past RASI-related hyperkalemia to a 12-week run-in phase for optimization of GDMT with patiromer. The trial was conducted at nearly 400 centers in 21 countries.

RASI medication could be optimized in 85% of the cohort, from which 878 patients were randomly assigned either to continue optimized GDMT with patiromer or to have the potassium-sequestrant replaced with a placebo.

The patients on patiromer showed a 0.03-mEq/L mean rise in serum potassium levels from randomization to the end of the study, the primary endpoint, compared with a 0.13 mEq/L mean increase for those in the control group (P < .001), Dr. Butler reported.

The win ratio for a RASI-use score hierarchically featuring cardiovascular death and CV hospitalization for hyperkalemia at several levels of severity was 1.25 (95% confidence interval, 1.003-1.564; P = .048), favoring the patiromer group. The win ratio solely for hyperkalemia-related events also favored patients on patiromer, at 1.53 (95% CI, 1.23-1.91; P < .001).

Patiromer also seemed well tolerated, Dr. Butler said.

Hyperkalemia is “one of the most common excuses” from clinicians for failing to up-titrate RASI medicine in patients with heart failure, Dr. Januzzi said. DIAMOND was less about patiromer itself than about ways “to facilitate better GDMT, where we’re really falling short of the mark. During the run-in phase they were able to get the vast majority of individuals to target, which to me is a critically important point, and emblematic of the need for things that facilitate this kind of excellent care.”

DIAMOND was funded by Vifor Pharma. Dr. Butler disclosed receiving consulting fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana Medical, and Vifor Pharma. Dr. Januzzi disclosed receiving consultant fees or honoraria from Abbott Laboratories, Imbria, Jana Care, Novartis, Prevencio, and Roche Diagnostics; serving on a data safety monitoring board for AbbVie, Amgen, Bayer Healthcare Pharmaceuticals, Beyer, CVRx, and Takeda Pharmaceuticals North America; and receiving research grants from Abbott Laboratories, Janssen, and Vifor Pharma.

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

Several of the core medications for patients with heart failure with reduced ejection fraction (HFrEF) come with a well-known risk of causing hyperkalemia, to which many clinicians respond by pulling back on dosing or withdrawing the culprit drug.

But accompanying renin-angiotensin system–inhibiting agents with the potassium-sequestrant patiromer (Veltassa, Vifor Pharma) appears to shield patients against hyperkalemia enough that they can take more RASI medications at higher doses, suggests a randomized, a controlled study.

Catherine Hackett/MDedge News

The DIAMOND trial’s HFrEF patients, who had current or a history of RASI-related hyperkalemia, added either patiromer or placebo to their guideline-directed medical therapy (GDMT), which includes, even emphasizes, the culprit medication. They include ACE inhibitors, angiotensin-receptor blockers (ARBs), angiotensin-receptor/neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs).

Those taking patiromer tolerated more intense RASI therapy – including MRAs, which are especially prone to causing hyperkalemia – than the patients assigned to placebo. They also maintained lower potassium concentrations and experienced fewer clinically important hyperkalemia episodes, reported Javed Butler, MD, MPH, MBA, Baylor Scott and White Research Institute, Dallas, at the annual scientific sessions of the American College of Cardiology.

The apparent benefit from patiromer came in part from an advantage for a composite hyperkalemia-event endpoint that included mortality, Dr. Butler noted. That advantage seemed to hold regardless of age, sex, body mass index, HFrEF symptom severity, or initial natriuretic peptide levels.

Patients who took patiromer, compared with those who took placebo, showed a 37% reduction in risk for hyperkalemia (P = .006), defined as potassium levels exceeding 5.5 mEq/L, over a median follow-up of 27 weeks. They were 38% less likely to have their MRA dosage reduced to below target level (P = .006).

More patients in the patiromer group than in the control group attained at least 50% of target dosage for MRAs and ACE inhibitors, ARBs, or ARNIs (92% vs. 87%; P = .015).

Patients with HFrEF are unlikely to achieve best possible outcomes without GDMT optimization, but failure to optimize is often attributed to hyperkalemia concerns. DIAMOND, Dr. Butler said, suggests that, by adding the potassium sequestrant to GDMT, “you can simultaneously control potassium and optimize RASI therapy.” Many clinicians seem to believe they can achieve only one or the other.

DIAMOND was too underpowered to show whether preventing hyperkalemia with patiromer could improve clinical outcomes. But failure to optimize RASI medication in HFrEF can worsen risk for heart failure events and death. So “it stands to reason that optimization of RASI therapy without a concomitant risk of hyperkalemia may, in the long run, lead to better outcomes for these patients,” Dr. Butler said in an interview.

Given the drug’s ability to keep potassium levels in check during RASI therapy, Dr. Butler said, “hypokalemia should not be a reason for suboptimal therapy.”

Patiromer and other potassium sequestrants have been available in the United States and Europe for 4-6 years, but their value as adjuncts to RASI medication in HFrEF or other heart failure has been unclear.

Courtesy Massachusetts General Hospital

“There’s a good opportunity to expand the use of the drug. The question is, in whom and when?” James L. Januzzi, MD, Massachusetts General Hospital, Boston, said in an interview.

Some HFrEF patients on GDMT “should be treated with patiromer. The bigger question is, should we give someone who has a history of hyperkalemia another chance at GDMT before we treat them with patiromer? Because they may not necessarily develop hyperkalemia a second time,” said Dr. Januzzi, who was on the DIAMOND endpoint-adjudication committee.

Among the most notable findings of the trial, he said, is that the number of people who developed hyperkalemia on RASI medication, although significantly elevated, “wasn’t as high as they expected it would be,” he said. “The data from DIAMOND argue that if a really significant majority does not become hyperkalemic on rechallenge, jumping straight to a potassium-binding drug may be premature.”

Physicians across specialties can differ in how they interpret potassium-level elevation and can use various cut points to flag when to stop RASI medication or at least hold back on up-titration, Dr. Butler observed. “Cardiologists have a different threshold of potassium that they tolerate than say, for instance, a nephrologist.”

Useful, then, might be a way to tell which patients are most likely to develop hyperkalemia with RASI up-titration and so might benefit from a potassium-binding agent right away. But DIAMOND, Dr. Butler said, “does not necessarily define any patient phenotype or any potassium level where we would say that you should use a potassium binder.”

The trial entered 1,642 patients with HFrEF and current or past RASI-related hyperkalemia to a 12-week run-in phase for optimization of GDMT with patiromer. The trial was conducted at nearly 400 centers in 21 countries.

RASI medication could be optimized in 85% of the cohort, from which 878 patients were randomly assigned either to continue optimized GDMT with patiromer or to have the potassium-sequestrant replaced with a placebo.

The patients on patiromer showed a 0.03-mEq/L mean rise in serum potassium levels from randomization to the end of the study, the primary endpoint, compared with a 0.13 mEq/L mean increase for those in the control group (P < .001), Dr. Butler reported.

The win ratio for a RASI-use score hierarchically featuring cardiovascular death and CV hospitalization for hyperkalemia at several levels of severity was 1.25 (95% confidence interval, 1.003-1.564; P = .048), favoring the patiromer group. The win ratio solely for hyperkalemia-related events also favored patients on patiromer, at 1.53 (95% CI, 1.23-1.91; P < .001).

Patiromer also seemed well tolerated, Dr. Butler said.

Hyperkalemia is “one of the most common excuses” from clinicians for failing to up-titrate RASI medicine in patients with heart failure, Dr. Januzzi said. DIAMOND was less about patiromer itself than about ways “to facilitate better GDMT, where we’re really falling short of the mark. During the run-in phase they were able to get the vast majority of individuals to target, which to me is a critically important point, and emblematic of the need for things that facilitate this kind of excellent care.”

DIAMOND was funded by Vifor Pharma. Dr. Butler disclosed receiving consulting fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana Medical, and Vifor Pharma. Dr. Januzzi disclosed receiving consultant fees or honoraria from Abbott Laboratories, Imbria, Jana Care, Novartis, Prevencio, and Roche Diagnostics; serving on a data safety monitoring board for AbbVie, Amgen, Bayer Healthcare Pharmaceuticals, Beyer, CVRx, and Takeda Pharmaceuticals North America; and receiving research grants from Abbott Laboratories, Janssen, and Vifor Pharma.

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

Several of the core medications for patients with heart failure with reduced ejection fraction (HFrEF) come with a well-known risk of causing hyperkalemia, to which many clinicians respond by pulling back on dosing or withdrawing the culprit drug.

But accompanying renin-angiotensin system–inhibiting agents with the potassium-sequestrant patiromer (Veltassa, Vifor Pharma) appears to shield patients against hyperkalemia enough that they can take more RASI medications at higher doses, suggests a randomized, a controlled study.

Catherine Hackett/MDedge News

The DIAMOND trial’s HFrEF patients, who had current or a history of RASI-related hyperkalemia, added either patiromer or placebo to their guideline-directed medical therapy (GDMT), which includes, even emphasizes, the culprit medication. They include ACE inhibitors, angiotensin-receptor blockers (ARBs), angiotensin-receptor/neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs).

Those taking patiromer tolerated more intense RASI therapy – including MRAs, which are especially prone to causing hyperkalemia – than the patients assigned to placebo. They also maintained lower potassium concentrations and experienced fewer clinically important hyperkalemia episodes, reported Javed Butler, MD, MPH, MBA, Baylor Scott and White Research Institute, Dallas, at the annual scientific sessions of the American College of Cardiology.

The apparent benefit from patiromer came in part from an advantage for a composite hyperkalemia-event endpoint that included mortality, Dr. Butler noted. That advantage seemed to hold regardless of age, sex, body mass index, HFrEF symptom severity, or initial natriuretic peptide levels.

Patients who took patiromer, compared with those who took placebo, showed a 37% reduction in risk for hyperkalemia (P = .006), defined as potassium levels exceeding 5.5 mEq/L, over a median follow-up of 27 weeks. They were 38% less likely to have their MRA dosage reduced to below target level (P = .006).

More patients in the patiromer group than in the control group attained at least 50% of target dosage for MRAs and ACE inhibitors, ARBs, or ARNIs (92% vs. 87%; P = .015).

Patients with HFrEF are unlikely to achieve best possible outcomes without GDMT optimization, but failure to optimize is often attributed to hyperkalemia concerns. DIAMOND, Dr. Butler said, suggests that, by adding the potassium sequestrant to GDMT, “you can simultaneously control potassium and optimize RASI therapy.” Many clinicians seem to believe they can achieve only one or the other.

DIAMOND was too underpowered to show whether preventing hyperkalemia with patiromer could improve clinical outcomes. But failure to optimize RASI medication in HFrEF can worsen risk for heart failure events and death. So “it stands to reason that optimization of RASI therapy without a concomitant risk of hyperkalemia may, in the long run, lead to better outcomes for these patients,” Dr. Butler said in an interview.

Given the drug’s ability to keep potassium levels in check during RASI therapy, Dr. Butler said, “hypokalemia should not be a reason for suboptimal therapy.”

Patiromer and other potassium sequestrants have been available in the United States and Europe for 4-6 years, but their value as adjuncts to RASI medication in HFrEF or other heart failure has been unclear.

Courtesy Massachusetts General Hospital

“There’s a good opportunity to expand the use of the drug. The question is, in whom and when?” James L. Januzzi, MD, Massachusetts General Hospital, Boston, said in an interview.

Some HFrEF patients on GDMT “should be treated with patiromer. The bigger question is, should we give someone who has a history of hyperkalemia another chance at GDMT before we treat them with patiromer? Because they may not necessarily develop hyperkalemia a second time,” said Dr. Januzzi, who was on the DIAMOND endpoint-adjudication committee.

Among the most notable findings of the trial, he said, is that the number of people who developed hyperkalemia on RASI medication, although significantly elevated, “wasn’t as high as they expected it would be,” he said. “The data from DIAMOND argue that if a really significant majority does not become hyperkalemic on rechallenge, jumping straight to a potassium-binding drug may be premature.”

Physicians across specialties can differ in how they interpret potassium-level elevation and can use various cut points to flag when to stop RASI medication or at least hold back on up-titration, Dr. Butler observed. “Cardiologists have a different threshold of potassium that they tolerate than say, for instance, a nephrologist.”

Useful, then, might be a way to tell which patients are most likely to develop hyperkalemia with RASI up-titration and so might benefit from a potassium-binding agent right away. But DIAMOND, Dr. Butler said, “does not necessarily define any patient phenotype or any potassium level where we would say that you should use a potassium binder.”

The trial entered 1,642 patients with HFrEF and current or past RASI-related hyperkalemia to a 12-week run-in phase for optimization of GDMT with patiromer. The trial was conducted at nearly 400 centers in 21 countries.

RASI medication could be optimized in 85% of the cohort, from which 878 patients were randomly assigned either to continue optimized GDMT with patiromer or to have the potassium-sequestrant replaced with a placebo.

The patients on patiromer showed a 0.03-mEq/L mean rise in serum potassium levels from randomization to the end of the study, the primary endpoint, compared with a 0.13 mEq/L mean increase for those in the control group (P < .001), Dr. Butler reported.

The win ratio for a RASI-use score hierarchically featuring cardiovascular death and CV hospitalization for hyperkalemia at several levels of severity was 1.25 (95% confidence interval, 1.003-1.564; P = .048), favoring the patiromer group. The win ratio solely for hyperkalemia-related events also favored patients on patiromer, at 1.53 (95% CI, 1.23-1.91; P < .001).

Patiromer also seemed well tolerated, Dr. Butler said.

Hyperkalemia is “one of the most common excuses” from clinicians for failing to up-titrate RASI medicine in patients with heart failure, Dr. Januzzi said. DIAMOND was less about patiromer itself than about ways “to facilitate better GDMT, where we’re really falling short of the mark. During the run-in phase they were able to get the vast majority of individuals to target, which to me is a critically important point, and emblematic of the need for things that facilitate this kind of excellent care.”

DIAMOND was funded by Vifor Pharma. Dr. Butler disclosed receiving consulting fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana Medical, and Vifor Pharma. Dr. Januzzi disclosed receiving consultant fees or honoraria from Abbott Laboratories, Imbria, Jana Care, Novartis, Prevencio, and Roche Diagnostics; serving on a data safety monitoring board for AbbVie, Amgen, Bayer Healthcare Pharmaceuticals, Beyer, CVRx, and Takeda Pharmaceuticals North America; and receiving research grants from Abbott Laboratories, Janssen, and Vifor Pharma.

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