Diabetes

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

An artificial intelligence (AI)–based predictive tool may be able to identify type 1 diabetes in children earlier, before they are diagnosed as a result of potentially fatal diabetic ketoacidosis (DKA), suggests a new U.K. study.

The tool was developed by Julia Townson, PhD, senior trial manager in children and young people at Cardiff University, U.K., and colleagues.

Her team had previously shown that children who develop type 1 diabetes have a different pattern of contact with primary care in the 6 months leading up to their diagnosis.

Symptoms of type 1 diabetes include going to the toilet more and being thirsty, tired, and thin, but GPs can still miss these signs.

So they tested different combinations of factors from GP records – such as urinary tract infections or bedwetting, being prescribed antibiotics or family history of type 1 diabetes – in approximately 1 million children in Wales, more than 2,000 of whom had been diagnosed with type 1 diabetes, to train the predictive tool.

In a separate study of around 1.5 million children in England, they found that the algorithm could identify type 1 diabetes in 75% of affected children 11 days earlier than without the tool, if it was set up as an alert at every one in 10 general practice consultations.

Dr. Townson presented her research at the recent Diabetes UK Professional Conference 2022.
 

One-quarter of kids diagnosed with type 1 diabetes are in DKA

During her presentation, Dr. Townson explained that, in the U.K., approximately 25% of children with type 1 diabetes are diagnosed while they are in DKA, a figure that has remained unchanged for 25 years.

“We know that delayed- and misdiagnosis are the most common reasons for a child presenting in DKA at diagnosis,” she said. “And of course, the reason why it’s so important to prevent presentation in DKA is because of the considerable morbidity and potentially mortality associated with it.”

Indeed, with a simple internet search, Dr. Townson was able to identify four children who lost their lives to DKA in the past 8 years in the U.K.

“It’s encouraging to see that this research could save many families a potentially traumatic trip to the hospital by helping family doctors diagnose type 1 diabetes more rapidly,” Conor McKeever, research communications manager at the type 1 diabetes charity JDRF, told this news organization.

“This approach could go hand-in-hand with population screening, which has the potential to identify people at high risk of developing type 1 diabetes before they experience any symptoms,” he added. The hope is that “far fewer families experience DKA at the start of their type 1 diabetes journey.”

“Finding a way to catch the condition and treat it early could help to avoid emergency hospital treatment and save lives,” agreed Lucy Chambers, PhD, head of research communications at Diabetes UK, which funded the research.
 

How to integrate tool into GP systems

“We are now looking to see how this tool might work with primary care computer systems,” Dr. Townson said. She said in an interview that they are exploring “how it could be ‘bolted’ on to the GP’s software system.”

“It works on many different levels, but one level is frequency of consultations in relation to the frequency of previous consultations, so it needs to be able to ‘look’ through the electronic health records, at the time of the consultation, to come up with a predictive score.”

Dr. Townson said it is not clear how “easy it will be to integrate it into current systems, and I do not know of any other machine learning applications which have been used like this in primary care.”

“But we are hopeful, and we have started to contact companies who are involved in providing these systems.”

The research was funded by Diabetes UK, and the Clinical Trials Unit was funded by Health and Care Research Wales. No relevant financial relationships were declared.

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

An artificial intelligence (AI)–based predictive tool may be able to identify type 1 diabetes in children earlier, before they are diagnosed as a result of potentially fatal diabetic ketoacidosis (DKA), suggests a new U.K. study.

The tool was developed by Julia Townson, PhD, senior trial manager in children and young people at Cardiff University, U.K., and colleagues.

Her team had previously shown that children who develop type 1 diabetes have a different pattern of contact with primary care in the 6 months leading up to their diagnosis.

Symptoms of type 1 diabetes include going to the toilet more and being thirsty, tired, and thin, but GPs can still miss these signs.

So they tested different combinations of factors from GP records – such as urinary tract infections or bedwetting, being prescribed antibiotics or family history of type 1 diabetes – in approximately 1 million children in Wales, more than 2,000 of whom had been diagnosed with type 1 diabetes, to train the predictive tool.

In a separate study of around 1.5 million children in England, they found that the algorithm could identify type 1 diabetes in 75% of affected children 11 days earlier than without the tool, if it was set up as an alert at every one in 10 general practice consultations.

Dr. Townson presented her research at the recent Diabetes UK Professional Conference 2022.
 

One-quarter of kids diagnosed with type 1 diabetes are in DKA

During her presentation, Dr. Townson explained that, in the U.K., approximately 25% of children with type 1 diabetes are diagnosed while they are in DKA, a figure that has remained unchanged for 25 years.

“We know that delayed- and misdiagnosis are the most common reasons for a child presenting in DKA at diagnosis,” she said. “And of course, the reason why it’s so important to prevent presentation in DKA is because of the considerable morbidity and potentially mortality associated with it.”

Indeed, with a simple internet search, Dr. Townson was able to identify four children who lost their lives to DKA in the past 8 years in the U.K.

“It’s encouraging to see that this research could save many families a potentially traumatic trip to the hospital by helping family doctors diagnose type 1 diabetes more rapidly,” Conor McKeever, research communications manager at the type 1 diabetes charity JDRF, told this news organization.

“This approach could go hand-in-hand with population screening, which has the potential to identify people at high risk of developing type 1 diabetes before they experience any symptoms,” he added. The hope is that “far fewer families experience DKA at the start of their type 1 diabetes journey.”

“Finding a way to catch the condition and treat it early could help to avoid emergency hospital treatment and save lives,” agreed Lucy Chambers, PhD, head of research communications at Diabetes UK, which funded the research.
 

How to integrate tool into GP systems

“We are now looking to see how this tool might work with primary care computer systems,” Dr. Townson said. She said in an interview that they are exploring “how it could be ‘bolted’ on to the GP’s software system.”

“It works on many different levels, but one level is frequency of consultations in relation to the frequency of previous consultations, so it needs to be able to ‘look’ through the electronic health records, at the time of the consultation, to come up with a predictive score.”

Dr. Townson said it is not clear how “easy it will be to integrate it into current systems, and I do not know of any other machine learning applications which have been used like this in primary care.”

“But we are hopeful, and we have started to contact companies who are involved in providing these systems.”

The research was funded by Diabetes UK, and the Clinical Trials Unit was funded by Health and Care Research Wales. No relevant financial relationships were declared.

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

An artificial intelligence (AI)–based predictive tool may be able to identify type 1 diabetes in children earlier, before they are diagnosed as a result of potentially fatal diabetic ketoacidosis (DKA), suggests a new U.K. study.

The tool was developed by Julia Townson, PhD, senior trial manager in children and young people at Cardiff University, U.K., and colleagues.

Her team had previously shown that children who develop type 1 diabetes have a different pattern of contact with primary care in the 6 months leading up to their diagnosis.

Symptoms of type 1 diabetes include going to the toilet more and being thirsty, tired, and thin, but GPs can still miss these signs.

So they tested different combinations of factors from GP records – such as urinary tract infections or bedwetting, being prescribed antibiotics or family history of type 1 diabetes – in approximately 1 million children in Wales, more than 2,000 of whom had been diagnosed with type 1 diabetes, to train the predictive tool.

In a separate study of around 1.5 million children in England, they found that the algorithm could identify type 1 diabetes in 75% of affected children 11 days earlier than without the tool, if it was set up as an alert at every one in 10 general practice consultations.

Dr. Townson presented her research at the recent Diabetes UK Professional Conference 2022.
 

One-quarter of kids diagnosed with type 1 diabetes are in DKA

During her presentation, Dr. Townson explained that, in the U.K., approximately 25% of children with type 1 diabetes are diagnosed while they are in DKA, a figure that has remained unchanged for 25 years.

“We know that delayed- and misdiagnosis are the most common reasons for a child presenting in DKA at diagnosis,” she said. “And of course, the reason why it’s so important to prevent presentation in DKA is because of the considerable morbidity and potentially mortality associated with it.”

Indeed, with a simple internet search, Dr. Townson was able to identify four children who lost their lives to DKA in the past 8 years in the U.K.

“It’s encouraging to see that this research could save many families a potentially traumatic trip to the hospital by helping family doctors diagnose type 1 diabetes more rapidly,” Conor McKeever, research communications manager at the type 1 diabetes charity JDRF, told this news organization.

“This approach could go hand-in-hand with population screening, which has the potential to identify people at high risk of developing type 1 diabetes before they experience any symptoms,” he added. The hope is that “far fewer families experience DKA at the start of their type 1 diabetes journey.”

“Finding a way to catch the condition and treat it early could help to avoid emergency hospital treatment and save lives,” agreed Lucy Chambers, PhD, head of research communications at Diabetes UK, which funded the research.
 

How to integrate tool into GP systems

“We are now looking to see how this tool might work with primary care computer systems,” Dr. Townson said. She said in an interview that they are exploring “how it could be ‘bolted’ on to the GP’s software system.”

“It works on many different levels, but one level is frequency of consultations in relation to the frequency of previous consultations, so it needs to be able to ‘look’ through the electronic health records, at the time of the consultation, to come up with a predictive score.”

Dr. Townson said it is not clear how “easy it will be to integrate it into current systems, and I do not know of any other machine learning applications which have been used like this in primary care.”

“But we are hopeful, and we have started to contact companies who are involved in providing these systems.”

The research was funded by Diabetes UK, and the Clinical Trials Unit was funded by Health and Care Research Wales. No relevant financial relationships were declared.

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

A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.

The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).

Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter

“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”

The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.

Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”

The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.

Peggy Peterson Photograph

Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.

However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.

Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.


 

A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.

The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).

Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter

“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”

The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.

Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”

The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.

Peggy Peterson Photograph

Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.

However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.

Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.


 

A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.

The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).

Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter

“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”

The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.

Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”

The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.

Peggy Peterson Photograph

Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.

However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.

Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.


 

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

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

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

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

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

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

WASHINGTON – Results from new analyses further fleshed out the potent effect by the investigational SGLT1&2 inhibitor sotagliflozin on major cardiovascular adverse events in patients with type 2 diabetes, chronic kidney disease, and at high risk for cardiovascular disease in the SCORED trial that randomized more than 10,000 patients.

In prespecified, secondary analyses of the SCORED results, treatment with sotagliflozin during a median of 16 months was linked to a significant 21% risk reduction relative to placebo for the combined incidence of total major adverse cardiovascular events (MACE), which included cardiovascular death, first and recurrent episodes of nonfatal MI, and nonfatal stroke among the 5,144 randomized patients who entered the trial with a history of cardiovascular disease (CVD), Deepak L. Bhatt, MD, said at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

Among the 5,440 patients in the study who did not have a history of CVD (although they did have at least one major risk factor or at least two minor risk factors), treatment with sotagliflozin was linked to a significant 26% relative risk reduction in total MACE events.

Part of these overall MACE benefits resulted from similar improvements from sotagliflozin treatment on the individual outcomes of total nonfatal MI and total nonfatal strokes. Treatment with sotagliflozin cut these MIs by a significant 31% in patients with a history of CVD relative to patients who received placebo, and by a relative 34% in those without a CVD event in their history, a difference compared with placebo that fell short of significance, said Dr. Bhatt, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Health, both in Boston.

Treatment with sotagliflozin also cut total nonfatal strokes by 31% relative to placebo in patients with a history of CVD, and by a relative 38% in those without a CVD history. Both differences fell short of significance.
 

An early MACE benefit and a stroke benefit

“This stroke benefit has not been clearly seen” with any agent from the closely related sodium-glucose cotransport-2 (SGLT2) inhibitor class, and “the MACE benefit appeared very early,” within 3 months from the start of sotagliflozin treatment, “which may be because of the SGLT1 inhibition,” Dr. Bhatt said during his report.

The SGLT1 receptor is the primary mechanism cells in the gut use to absorb glucose and galactose in the human gastrointestinal tract, Dr. Bhatt explained, while the SGLT2 receptor appears on kidney cells and is the major player in the reabsorption of filtered glucose. The SGLT2 inhibitor class includes the agents canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), while sotagliflozin inhibits both SGLT1 and SGLT2.

Main results from SCORED appeared in a report first released in late 2020, and showed that for the study’s primary endpoint treatment with sotagliflozin linked with a significant 26% relative risk reduction for the composite of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure (N Engl J Med. 2021 Jan 14;384[2]:129-39). Patient follow-up in SCORED was not as long as originally planned when the study stopped early due to a loss of funding from a sponsor that was triggered by the COVID-19 pandemic.

MACE results ‘heterogeneous’ from SGLT2 inhibitors

Sotagliflozin and agents from the SGLT2 inhibitor class “have been consistent” in their benefits for reducing cardiovascular death and hospitalization for heart failure, but for MACE, the results from the SGLT2 inhibitors “have been more heterogeneous,” and the effect of sotagliflozin on MACE “were different in SCORED,” commented Michelle L. O’Donoghue, MD, MPH, a cardiologist at Brigham and Women’s Hospital in Boston who was not involved with this work.

Mitchel L. Zoler/MDedge News

“The results suggest a benefit [from sotagliflozin] on atherosclerotic events, which could be a potential advantage” compared with the SGLT2 inhibitors, “but the heterogeneity of this effect” among these agents means that more confirmatory data are needed for sotagliflozin, Dr. O’Donoghue said in an interview.

“There is a lot of enthusiasm for the concept” of combined inhibition of the SGLT1 and 2 receptors, and if more evidence for unique benefits of this effect accumulate “it may lead to increased enthusiasm for sotagliflozin,” she said. “A lot will also depend on pricing decisions” for sotagliflozin, if it receives U.S. marketing approval from the Food and Drug Administration. Decisions about which agent from the SGLT2 inhibitor class to prescribe “are often being made based on price right now,” Dr. O’Donoghue said.

Lexicon Pharmaceuticals, the company developing sotagliflozin, has announced plans to resubmit its new drug application for sotagliflozin to the FDA later in 2022, with the agency’s approval decision likely occurring late in 2022 or sometime during 2023. In February, the company withdrew its December 2021 application to correct a “technical issue” it had found.

An additional analysis reported by Dr. Bhatt used combined data from SCORED as well as several additional randomized trials of sotagliflozin involving a total of more than 20,000 patients that showed a significant 21% reduction in the incidence of MACE compared with placebo.

During his talk, Dr. Bhatt said that sotagliflozin was potentially superior to the agents that inhibit only SGLT2. In an interview, he based this tentative assessment on at least four attributes of sotagliflozin that have emerged from trial results:

• The drug’s ability to significantly reduce MACE and to have this effect apparent within a few months of treatment onset;
• The significantly reduced rate of stroke with sotagliflozin (when patients are not subdivided into those with or without a history of CVD) that has not yet been seen with any SGLT2 inhibitor;
• The ability of sotagliflozin to reduce hemoglobin A1c levels in patients with type 2 diabetes even when their estimated glomerular filtration rate is less than 30 mL/min per 1.73 m², an effect not seen with SGLT2 inhibitors and possibly explained by sotagliflozin having an effect on gut absorption of glucose in addition to its SGLT2 inhibitory effect in the kidney;
• And the proven ability of sotagliflozin to be safe and effective when initiated in patients hospitalized for heart failure, a property that so far has only also been shown for the SGLT2 inhibitor empagliflozin in the EMPULSE trial (Nature Med. 2022 Mar;28: 568-74).

SCORED was sponsored by Sanofi and Lexicon Pharmaceuticals, the companies originally developing sotagliflozin, although with the withdrawal of Sanofi’s support, further development is now sponsored entirely by Lexicon. Dr. Bhatt received research funding from Sanofi and Lexicon that was paid to Brigham and Women’s Health, and he has been an advisor to numerous companies. Dr. O’Donoghue has been a consultant to Amgen, Janssen, and Novartis, and has received research funding from Amgen, AZ MedImmune, Intarcia, Janssen, Merck, and Novartis.
 

WASHINGTON – Results from new analyses further fleshed out the potent effect by the investigational SGLT1&2 inhibitor sotagliflozin on major cardiovascular adverse events in patients with type 2 diabetes, chronic kidney disease, and at high risk for cardiovascular disease in the SCORED trial that randomized more than 10,000 patients.

In prespecified, secondary analyses of the SCORED results, treatment with sotagliflozin during a median of 16 months was linked to a significant 21% risk reduction relative to placebo for the combined incidence of total major adverse cardiovascular events (MACE), which included cardiovascular death, first and recurrent episodes of nonfatal MI, and nonfatal stroke among the 5,144 randomized patients who entered the trial with a history of cardiovascular disease (CVD), Deepak L. Bhatt, MD, said at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

Among the 5,440 patients in the study who did not have a history of CVD (although they did have at least one major risk factor or at least two minor risk factors), treatment with sotagliflozin was linked to a significant 26% relative risk reduction in total MACE events.

Part of these overall MACE benefits resulted from similar improvements from sotagliflozin treatment on the individual outcomes of total nonfatal MI and total nonfatal strokes. Treatment with sotagliflozin cut these MIs by a significant 31% in patients with a history of CVD relative to patients who received placebo, and by a relative 34% in those without a CVD event in their history, a difference compared with placebo that fell short of significance, said Dr. Bhatt, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Health, both in Boston.

Treatment with sotagliflozin also cut total nonfatal strokes by 31% relative to placebo in patients with a history of CVD, and by a relative 38% in those without a CVD history. Both differences fell short of significance.
 

An early MACE benefit and a stroke benefit

“This stroke benefit has not been clearly seen” with any agent from the closely related sodium-glucose cotransport-2 (SGLT2) inhibitor class, and “the MACE benefit appeared very early,” within 3 months from the start of sotagliflozin treatment, “which may be because of the SGLT1 inhibition,” Dr. Bhatt said during his report.

The SGLT1 receptor is the primary mechanism cells in the gut use to absorb glucose and galactose in the human gastrointestinal tract, Dr. Bhatt explained, while the SGLT2 receptor appears on kidney cells and is the major player in the reabsorption of filtered glucose. The SGLT2 inhibitor class includes the agents canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), while sotagliflozin inhibits both SGLT1 and SGLT2.

Main results from SCORED appeared in a report first released in late 2020, and showed that for the study’s primary endpoint treatment with sotagliflozin linked with a significant 26% relative risk reduction for the composite of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure (N Engl J Med. 2021 Jan 14;384[2]:129-39). Patient follow-up in SCORED was not as long as originally planned when the study stopped early due to a loss of funding from a sponsor that was triggered by the COVID-19 pandemic.

MACE results ‘heterogeneous’ from SGLT2 inhibitors

Sotagliflozin and agents from the SGLT2 inhibitor class “have been consistent” in their benefits for reducing cardiovascular death and hospitalization for heart failure, but for MACE, the results from the SGLT2 inhibitors “have been more heterogeneous,” and the effect of sotagliflozin on MACE “were different in SCORED,” commented Michelle L. O’Donoghue, MD, MPH, a cardiologist at Brigham and Women’s Hospital in Boston who was not involved with this work.

Mitchel L. Zoler/MDedge News

“The results suggest a benefit [from sotagliflozin] on atherosclerotic events, which could be a potential advantage” compared with the SGLT2 inhibitors, “but the heterogeneity of this effect” among these agents means that more confirmatory data are needed for sotagliflozin, Dr. O’Donoghue said in an interview.

“There is a lot of enthusiasm for the concept” of combined inhibition of the SGLT1 and 2 receptors, and if more evidence for unique benefits of this effect accumulate “it may lead to increased enthusiasm for sotagliflozin,” she said. “A lot will also depend on pricing decisions” for sotagliflozin, if it receives U.S. marketing approval from the Food and Drug Administration. Decisions about which agent from the SGLT2 inhibitor class to prescribe “are often being made based on price right now,” Dr. O’Donoghue said.

Lexicon Pharmaceuticals, the company developing sotagliflozin, has announced plans to resubmit its new drug application for sotagliflozin to the FDA later in 2022, with the agency’s approval decision likely occurring late in 2022 or sometime during 2023. In February, the company withdrew its December 2021 application to correct a “technical issue” it had found.

An additional analysis reported by Dr. Bhatt used combined data from SCORED as well as several additional randomized trials of sotagliflozin involving a total of more than 20,000 patients that showed a significant 21% reduction in the incidence of MACE compared with placebo.

During his talk, Dr. Bhatt said that sotagliflozin was potentially superior to the agents that inhibit only SGLT2. In an interview, he based this tentative assessment on at least four attributes of sotagliflozin that have emerged from trial results:

• The drug’s ability to significantly reduce MACE and to have this effect apparent within a few months of treatment onset;
• The significantly reduced rate of stroke with sotagliflozin (when patients are not subdivided into those with or without a history of CVD) that has not yet been seen with any SGLT2 inhibitor;
• The ability of sotagliflozin to reduce hemoglobin A1c levels in patients with type 2 diabetes even when their estimated glomerular filtration rate is less than 30 mL/min per 1.73 m², an effect not seen with SGLT2 inhibitors and possibly explained by sotagliflozin having an effect on gut absorption of glucose in addition to its SGLT2 inhibitory effect in the kidney;
• And the proven ability of sotagliflozin to be safe and effective when initiated in patients hospitalized for heart failure, a property that so far has only also been shown for the SGLT2 inhibitor empagliflozin in the EMPULSE trial (Nature Med. 2022 Mar;28: 568-74).

SCORED was sponsored by Sanofi and Lexicon Pharmaceuticals, the companies originally developing sotagliflozin, although with the withdrawal of Sanofi’s support, further development is now sponsored entirely by Lexicon. Dr. Bhatt received research funding from Sanofi and Lexicon that was paid to Brigham and Women’s Health, and he has been an advisor to numerous companies. Dr. O’Donoghue has been a consultant to Amgen, Janssen, and Novartis, and has received research funding from Amgen, AZ MedImmune, Intarcia, Janssen, Merck, and Novartis.
 

WASHINGTON – Results from new analyses further fleshed out the potent effect by the investigational SGLT1&2 inhibitor sotagliflozin on major cardiovascular adverse events in patients with type 2 diabetes, chronic kidney disease, and at high risk for cardiovascular disease in the SCORED trial that randomized more than 10,000 patients.

In prespecified, secondary analyses of the SCORED results, treatment with sotagliflozin during a median of 16 months was linked to a significant 21% risk reduction relative to placebo for the combined incidence of total major adverse cardiovascular events (MACE), which included cardiovascular death, first and recurrent episodes of nonfatal MI, and nonfatal stroke among the 5,144 randomized patients who entered the trial with a history of cardiovascular disease (CVD), Deepak L. Bhatt, MD, said at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

Among the 5,440 patients in the study who did not have a history of CVD (although they did have at least one major risk factor or at least two minor risk factors), treatment with sotagliflozin was linked to a significant 26% relative risk reduction in total MACE events.

Part of these overall MACE benefits resulted from similar improvements from sotagliflozin treatment on the individual outcomes of total nonfatal MI and total nonfatal strokes. Treatment with sotagliflozin cut these MIs by a significant 31% in patients with a history of CVD relative to patients who received placebo, and by a relative 34% in those without a CVD event in their history, a difference compared with placebo that fell short of significance, said Dr. Bhatt, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Health, both in Boston.

Treatment with sotagliflozin also cut total nonfatal strokes by 31% relative to placebo in patients with a history of CVD, and by a relative 38% in those without a CVD history. Both differences fell short of significance.
 

An early MACE benefit and a stroke benefit

“This stroke benefit has not been clearly seen” with any agent from the closely related sodium-glucose cotransport-2 (SGLT2) inhibitor class, and “the MACE benefit appeared very early,” within 3 months from the start of sotagliflozin treatment, “which may be because of the SGLT1 inhibition,” Dr. Bhatt said during his report.

The SGLT1 receptor is the primary mechanism cells in the gut use to absorb glucose and galactose in the human gastrointestinal tract, Dr. Bhatt explained, while the SGLT2 receptor appears on kidney cells and is the major player in the reabsorption of filtered glucose. The SGLT2 inhibitor class includes the agents canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), while sotagliflozin inhibits both SGLT1 and SGLT2.

Main results from SCORED appeared in a report first released in late 2020, and showed that for the study’s primary endpoint treatment with sotagliflozin linked with a significant 26% relative risk reduction for the composite of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure (N Engl J Med. 2021 Jan 14;384[2]:129-39). Patient follow-up in SCORED was not as long as originally planned when the study stopped early due to a loss of funding from a sponsor that was triggered by the COVID-19 pandemic.

MACE results ‘heterogeneous’ from SGLT2 inhibitors

Sotagliflozin and agents from the SGLT2 inhibitor class “have been consistent” in their benefits for reducing cardiovascular death and hospitalization for heart failure, but for MACE, the results from the SGLT2 inhibitors “have been more heterogeneous,” and the effect of sotagliflozin on MACE “were different in SCORED,” commented Michelle L. O’Donoghue, MD, MPH, a cardiologist at Brigham and Women’s Hospital in Boston who was not involved with this work.

Mitchel L. Zoler/MDedge News

“The results suggest a benefit [from sotagliflozin] on atherosclerotic events, which could be a potential advantage” compared with the SGLT2 inhibitors, “but the heterogeneity of this effect” among these agents means that more confirmatory data are needed for sotagliflozin, Dr. O’Donoghue said in an interview.

“There is a lot of enthusiasm for the concept” of combined inhibition of the SGLT1 and 2 receptors, and if more evidence for unique benefits of this effect accumulate “it may lead to increased enthusiasm for sotagliflozin,” she said. “A lot will also depend on pricing decisions” for sotagliflozin, if it receives U.S. marketing approval from the Food and Drug Administration. Decisions about which agent from the SGLT2 inhibitor class to prescribe “are often being made based on price right now,” Dr. O’Donoghue said.

Lexicon Pharmaceuticals, the company developing sotagliflozin, has announced plans to resubmit its new drug application for sotagliflozin to the FDA later in 2022, with the agency’s approval decision likely occurring late in 2022 or sometime during 2023. In February, the company withdrew its December 2021 application to correct a “technical issue” it had found.

An additional analysis reported by Dr. Bhatt used combined data from SCORED as well as several additional randomized trials of sotagliflozin involving a total of more than 20,000 patients that showed a significant 21% reduction in the incidence of MACE compared with placebo.

During his talk, Dr. Bhatt said that sotagliflozin was potentially superior to the agents that inhibit only SGLT2. In an interview, he based this tentative assessment on at least four attributes of sotagliflozin that have emerged from trial results:

• The drug’s ability to significantly reduce MACE and to have this effect apparent within a few months of treatment onset;
• The significantly reduced rate of stroke with sotagliflozin (when patients are not subdivided into those with or without a history of CVD) that has not yet been seen with any SGLT2 inhibitor;
• The ability of sotagliflozin to reduce hemoglobin A1c levels in patients with type 2 diabetes even when their estimated glomerular filtration rate is less than 30 mL/min per 1.73 m², an effect not seen with SGLT2 inhibitors and possibly explained by sotagliflozin having an effect on gut absorption of glucose in addition to its SGLT2 inhibitory effect in the kidney;
• And the proven ability of sotagliflozin to be safe and effective when initiated in patients hospitalized for heart failure, a property that so far has only also been shown for the SGLT2 inhibitor empagliflozin in the EMPULSE trial (Nature Med. 2022 Mar;28: 568-74).

SCORED was sponsored by Sanofi and Lexicon Pharmaceuticals, the companies originally developing sotagliflozin, although with the withdrawal of Sanofi’s support, further development is now sponsored entirely by Lexicon. Dr. Bhatt received research funding from Sanofi and Lexicon that was paid to Brigham and Women’s Health, and he has been an advisor to numerous companies. Dr. O’Donoghue has been a consultant to Amgen, Janssen, and Novartis, and has received research funding from Amgen, AZ MedImmune, Intarcia, Janssen, Merck, and Novartis.
 

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

Among patients with diabetes, women are just as likely as men to suffer from sexual dysfunction, but their issues are overlooked, with the narrative focusing mainly on the impact of this issue on men, say experts.

Women with diabetes can experience reduced sexual desire, painful sex, reduced lubrication, and sexual distress, increasing the risk of depression, and such issues often go unnoticed despite treatments being available, said Kirsty Winkley, PhD, diabetes nurse and health psychologist, King’s College London.

There is also the “embarrassment factor” on the side of both the health care professional and the patient, she said in a session she chaired at the Diabetes UK Professional Conference 2022. Many women with diabetes “wouldn’t necessarily know” that their sexual dysfunction “is related to their diabetes,” she told this news organization.

For women, sexual health conversations are “often about contraception and pregnancy,” as well as menstrual disorders, genital infections, and hormone replacement therapy. “As health care professionals, you’re trained to focus on those things, and you’re not really considering there might be sexual dysfunction. If women aren’t aware that it’s related to diabetes, you’ve got the perfect situation where it goes under the radar.”

However, cochair Debbie Cooke, PhD, health psychologist at the University of Surrey in Guildford, explained that having psychotherapy embedded within the diabetes team and “integrated throughout the whole service” means that the problem can be identified and treatment offered.

The issue is that such integration is “very uncommon” and access needs to be improved, Dr. Cooke said in an interview.
 

Sexual dysfunction major predictor of depression in women

Jacqueline Fosbury, psychotherapy lead at Diabetes Care for You, Sussex Community NHS Foundation Trust, said that “intimate activity is clearly beneficial for emotional and physical health,” as it is associated with increased oxytocin release, the burning of calories, better immunity, and improved sleep.

Sexual dysfunction is common in people with diabetes, she noted. Poor glycemic control can “damage” blood vessels and nerves, causing reduced blood flow and loss of sensation in sexual organs.

A recent study led by Belgian researchers found that among more than 750 adults with diabetes, 36% of men and 33% of women reported sexual dysfunction.

Sexual dysfunction was more common in women with type 1 diabetes, at 36%, compared with 26% for those with type 2 diabetes. The most commonly reported issues were decreased sexual desire, lubrication problems, orgasmic dysfunction, and pain. Body image problems and fear of hypoglycemia also affect sexuality and intimacy, leading to “sexual distress.”

Moreover, Ms. Fosbury said female sexual dysfunction has been identified as a “major predictor” of depression, which in turn reduces libido.

Treatments for women can include lubricants, local estrogen, and medications that are prescribed off-label, such as sildenafil. The same is true of testosterone therapy, which can be used to boost libido.
 

Couples therapy?

Next, Trudy Hannington, a psychosexual therapist with Leger Clinic, Doncaster, U.K., talked about how to use an integrated approach to address sexuality overall in people with diabetes.

She said this should be seen in a biopsychosocial context, with emphasis on the couple, on sensation and communication, and sexual growth, as well as changes in daily routines.

There should be a move away from “penetrative sex,” Ms. Hannington said, with the goal being “enjoyment, not orgasm.” Pleasure should be facilitated and the opportunities for “performance pressure and/or anxiety” reduced.

She discussed the case of Marie, a 27-year-old woman with type 1 diabetes who had been referred with painful sex and vaginal dryness. Marie had “never experienced orgasm,” despite being in a same-sex relationship with Emily.

Marie’s treatment involved a sexual growth program, to which Emily was invited, as well as recommendations to use lubricants, vibrators, and to try sildenafil.
 

Prioritize women

Ms. Fosbury reiterated that, in men, sexual dysfunction is “readily identified as a complication of diabetes” and is described as “traumatic” and “crucial to well-being.” It is also seen as “easy to treat” with medication, such as that for erectile dysfunction.

It is therefore crucial to talk to women with diabetes about possible sexual dysfunction, and the scene must be set before the appointment to explain that the subject will be broached. In addition, handouts and leaflets should be available for patients in the clinic so they can read about female sexual health and to lower the stigma around discussing it.

“Cultural stereotypes diminish the importance of female sexuality and prevent us from providing equal consideration to the sexual difficulties of our patients,” she concluded.

No funding declared. No relevant financial relationships declared.

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

Among patients with diabetes, women are just as likely as men to suffer from sexual dysfunction, but their issues are overlooked, with the narrative focusing mainly on the impact of this issue on men, say experts.

Women with diabetes can experience reduced sexual desire, painful sex, reduced lubrication, and sexual distress, increasing the risk of depression, and such issues often go unnoticed despite treatments being available, said Kirsty Winkley, PhD, diabetes nurse and health psychologist, King’s College London.

There is also the “embarrassment factor” on the side of both the health care professional and the patient, she said in a session she chaired at the Diabetes UK Professional Conference 2022. Many women with diabetes “wouldn’t necessarily know” that their sexual dysfunction “is related to their diabetes,” she told this news organization.

For women, sexual health conversations are “often about contraception and pregnancy,” as well as menstrual disorders, genital infections, and hormone replacement therapy. “As health care professionals, you’re trained to focus on those things, and you’re not really considering there might be sexual dysfunction. If women aren’t aware that it’s related to diabetes, you’ve got the perfect situation where it goes under the radar.”

However, cochair Debbie Cooke, PhD, health psychologist at the University of Surrey in Guildford, explained that having psychotherapy embedded within the diabetes team and “integrated throughout the whole service” means that the problem can be identified and treatment offered.

The issue is that such integration is “very uncommon” and access needs to be improved, Dr. Cooke said in an interview.
 

Sexual dysfunction major predictor of depression in women

Jacqueline Fosbury, psychotherapy lead at Diabetes Care for You, Sussex Community NHS Foundation Trust, said that “intimate activity is clearly beneficial for emotional and physical health,” as it is associated with increased oxytocin release, the burning of calories, better immunity, and improved sleep.

Sexual dysfunction is common in people with diabetes, she noted. Poor glycemic control can “damage” blood vessels and nerves, causing reduced blood flow and loss of sensation in sexual organs.

A recent study led by Belgian researchers found that among more than 750 adults with diabetes, 36% of men and 33% of women reported sexual dysfunction.

Sexual dysfunction was more common in women with type 1 diabetes, at 36%, compared with 26% for those with type 2 diabetes. The most commonly reported issues were decreased sexual desire, lubrication problems, orgasmic dysfunction, and pain. Body image problems and fear of hypoglycemia also affect sexuality and intimacy, leading to “sexual distress.”

Moreover, Ms. Fosbury said female sexual dysfunction has been identified as a “major predictor” of depression, which in turn reduces libido.

Treatments for women can include lubricants, local estrogen, and medications that are prescribed off-label, such as sildenafil. The same is true of testosterone therapy, which can be used to boost libido.
 

Couples therapy?

Next, Trudy Hannington, a psychosexual therapist with Leger Clinic, Doncaster, U.K., talked about how to use an integrated approach to address sexuality overall in people with diabetes.

She said this should be seen in a biopsychosocial context, with emphasis on the couple, on sensation and communication, and sexual growth, as well as changes in daily routines.

There should be a move away from “penetrative sex,” Ms. Hannington said, with the goal being “enjoyment, not orgasm.” Pleasure should be facilitated and the opportunities for “performance pressure and/or anxiety” reduced.

She discussed the case of Marie, a 27-year-old woman with type 1 diabetes who had been referred with painful sex and vaginal dryness. Marie had “never experienced orgasm,” despite being in a same-sex relationship with Emily.

Marie’s treatment involved a sexual growth program, to which Emily was invited, as well as recommendations to use lubricants, vibrators, and to try sildenafil.
 

Prioritize women

Ms. Fosbury reiterated that, in men, sexual dysfunction is “readily identified as a complication of diabetes” and is described as “traumatic” and “crucial to well-being.” It is also seen as “easy to treat” with medication, such as that for erectile dysfunction.

It is therefore crucial to talk to women with diabetes about possible sexual dysfunction, and the scene must be set before the appointment to explain that the subject will be broached. In addition, handouts and leaflets should be available for patients in the clinic so they can read about female sexual health and to lower the stigma around discussing it.

“Cultural stereotypes diminish the importance of female sexuality and prevent us from providing equal consideration to the sexual difficulties of our patients,” she concluded.

No funding declared. No relevant financial relationships declared.

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

Among patients with diabetes, women are just as likely as men to suffer from sexual dysfunction, but their issues are overlooked, with the narrative focusing mainly on the impact of this issue on men, say experts.

Women with diabetes can experience reduced sexual desire, painful sex, reduced lubrication, and sexual distress, increasing the risk of depression, and such issues often go unnoticed despite treatments being available, said Kirsty Winkley, PhD, diabetes nurse and health psychologist, King’s College London.

There is also the “embarrassment factor” on the side of both the health care professional and the patient, she said in a session she chaired at the Diabetes UK Professional Conference 2022. Many women with diabetes “wouldn’t necessarily know” that their sexual dysfunction “is related to their diabetes,” she told this news organization.

For women, sexual health conversations are “often about contraception and pregnancy,” as well as menstrual disorders, genital infections, and hormone replacement therapy. “As health care professionals, you’re trained to focus on those things, and you’re not really considering there might be sexual dysfunction. If women aren’t aware that it’s related to diabetes, you’ve got the perfect situation where it goes under the radar.”

However, cochair Debbie Cooke, PhD, health psychologist at the University of Surrey in Guildford, explained that having psychotherapy embedded within the diabetes team and “integrated throughout the whole service” means that the problem can be identified and treatment offered.

The issue is that such integration is “very uncommon” and access needs to be improved, Dr. Cooke said in an interview.
 

Sexual dysfunction major predictor of depression in women

Jacqueline Fosbury, psychotherapy lead at Diabetes Care for You, Sussex Community NHS Foundation Trust, said that “intimate activity is clearly beneficial for emotional and physical health,” as it is associated with increased oxytocin release, the burning of calories, better immunity, and improved sleep.

Sexual dysfunction is common in people with diabetes, she noted. Poor glycemic control can “damage” blood vessels and nerves, causing reduced blood flow and loss of sensation in sexual organs.

A recent study led by Belgian researchers found that among more than 750 adults with diabetes, 36% of men and 33% of women reported sexual dysfunction.

Sexual dysfunction was more common in women with type 1 diabetes, at 36%, compared with 26% for those with type 2 diabetes. The most commonly reported issues were decreased sexual desire, lubrication problems, orgasmic dysfunction, and pain. Body image problems and fear of hypoglycemia also affect sexuality and intimacy, leading to “sexual distress.”

Moreover, Ms. Fosbury said female sexual dysfunction has been identified as a “major predictor” of depression, which in turn reduces libido.

Treatments for women can include lubricants, local estrogen, and medications that are prescribed off-label, such as sildenafil. The same is true of testosterone therapy, which can be used to boost libido.
 

Couples therapy?

Next, Trudy Hannington, a psychosexual therapist with Leger Clinic, Doncaster, U.K., talked about how to use an integrated approach to address sexuality overall in people with diabetes.

She said this should be seen in a biopsychosocial context, with emphasis on the couple, on sensation and communication, and sexual growth, as well as changes in daily routines.

There should be a move away from “penetrative sex,” Ms. Hannington said, with the goal being “enjoyment, not orgasm.” Pleasure should be facilitated and the opportunities for “performance pressure and/or anxiety” reduced.

She discussed the case of Marie, a 27-year-old woman with type 1 diabetes who had been referred with painful sex and vaginal dryness. Marie had “never experienced orgasm,” despite being in a same-sex relationship with Emily.

Marie’s treatment involved a sexual growth program, to which Emily was invited, as well as recommendations to use lubricants, vibrators, and to try sildenafil.
 

Prioritize women

Ms. Fosbury reiterated that, in men, sexual dysfunction is “readily identified as a complication of diabetes” and is described as “traumatic” and “crucial to well-being.” It is also seen as “easy to treat” with medication, such as that for erectile dysfunction.

It is therefore crucial to talk to women with diabetes about possible sexual dysfunction, and the scene must be set before the appointment to explain that the subject will be broached. In addition, handouts and leaflets should be available for patients in the clinic so they can read about female sexual health and to lower the stigma around discussing it.

“Cultural stereotypes diminish the importance of female sexuality and prevent us from providing equal consideration to the sexual difficulties of our patients,” she concluded.

No funding declared. No relevant financial relationships declared.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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