Cardiology

Officials have previously linked being overweight or obese to a greater risk for more severe COVID-19. A report today from the U.S. Centers for Disease Control and Prevention adds numbers and some nuance to the association.

Data from nearly 150,000 U.S. adults hospitalized with COVID-19 nationwide indicate that risk for more severe disease outcomes increases along with body mass index (BMI). The risk of COVID-19–related hospitalization and death associated with obesity was particularly high among people younger than 65.

“As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity,” the researchers note. They add that their findings suggest “progressively intensive management of COVID-19 might be needed for patients with more severe obesity.”

People with COVID-19 close to the border between a healthy and overweight BMI – from 23.7 kg/m² to 25.9 kg/m² – had the lowest risks for adverse outcomes.

The study was published online today in Morbidity and Mortality Weekly Report.
 

Greater need for critical care

The risk of ICU admission was particularly associated with severe obesity. For example, those with a BMI in the 40-44.9 kg/m² category had a 6% increased risk, which jumped to 16% higher among those with a BMI of 45 or greater.

Compared to people with a healthy BMI, the need for invasive mechanical ventilation was 12% more likely among overweight adults with a BMI of 25-29.2. The risked jumped to 108% greater among the most obese people, those with a BMI of 45 or greater, lead CDC researcher Lyudmyla Kompaniyets, PhD, and colleagues reported.

Moreover, the risks for hospitalization and death increased in a dose-response relationship with obesity.

For example, risks of being hospitalized were 7% greater for adults with a BMI between 30 and 34.9 and climbed to 33% greater for those with a BMI of 45. Risks were calculated as adjusted relative risks compared with people with a healthy BMI between 18.5 and 24.9.

Interestingly, being underweight was associated with elevated risk for COVID-19 hospitalization as well. For example, people with a BMI of less than 18.5 had a 20% greater chance of admission vs. people in the healthy BMI range. Unknown underlying medical conditions or issues related to nutrition or immune function could be contributing factors, the researchers note.
 

Elevated risk of dying

The risk of death in adults with obesity ranged from 8% higher in the 30-34.9 range up to 61% greater for those with a BMI of 45.

Chronic inflammation or impaired lung function from excess weight are possible reasons that higher BMI imparts greater risk, the researchers note.

The CDC researchers evaluated 148,494 adults from 238 hospitals participating in PHD-SR database. Because the study was limited to people hospitalized with COVID-19, the findings may not apply to all adults with COVID-19.

Another potential limitation is that investigators were unable to calculate BMI for all patients in the database because about 28% of participating hospitals did not report height and weight.

The study authors had no relevant financial relationships to disclose. 

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

Officials have previously linked being overweight or obese to a greater risk for more severe COVID-19. A report today from the U.S. Centers for Disease Control and Prevention adds numbers and some nuance to the association.

Data from nearly 150,000 U.S. adults hospitalized with COVID-19 nationwide indicate that risk for more severe disease outcomes increases along with body mass index (BMI). The risk of COVID-19–related hospitalization and death associated with obesity was particularly high among people younger than 65.

“As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity,” the researchers note. They add that their findings suggest “progressively intensive management of COVID-19 might be needed for patients with more severe obesity.”

People with COVID-19 close to the border between a healthy and overweight BMI – from 23.7 kg/m² to 25.9 kg/m² – had the lowest risks for adverse outcomes.

The study was published online today in Morbidity and Mortality Weekly Report.
 

Greater need for critical care

The risk of ICU admission was particularly associated with severe obesity. For example, those with a BMI in the 40-44.9 kg/m² category had a 6% increased risk, which jumped to 16% higher among those with a BMI of 45 or greater.

Compared to people with a healthy BMI, the need for invasive mechanical ventilation was 12% more likely among overweight adults with a BMI of 25-29.2. The risked jumped to 108% greater among the most obese people, those with a BMI of 45 or greater, lead CDC researcher Lyudmyla Kompaniyets, PhD, and colleagues reported.

Moreover, the risks for hospitalization and death increased in a dose-response relationship with obesity.

For example, risks of being hospitalized were 7% greater for adults with a BMI between 30 and 34.9 and climbed to 33% greater for those with a BMI of 45. Risks were calculated as adjusted relative risks compared with people with a healthy BMI between 18.5 and 24.9.

Interestingly, being underweight was associated with elevated risk for COVID-19 hospitalization as well. For example, people with a BMI of less than 18.5 had a 20% greater chance of admission vs. people in the healthy BMI range. Unknown underlying medical conditions or issues related to nutrition or immune function could be contributing factors, the researchers note.
 

Elevated risk of dying

The risk of death in adults with obesity ranged from 8% higher in the 30-34.9 range up to 61% greater for those with a BMI of 45.

Chronic inflammation or impaired lung function from excess weight are possible reasons that higher BMI imparts greater risk, the researchers note.

The CDC researchers evaluated 148,494 adults from 238 hospitals participating in PHD-SR database. Because the study was limited to people hospitalized with COVID-19, the findings may not apply to all adults with COVID-19.

Another potential limitation is that investigators were unable to calculate BMI for all patients in the database because about 28% of participating hospitals did not report height and weight.

The study authors had no relevant financial relationships to disclose. 

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

Officials have previously linked being overweight or obese to a greater risk for more severe COVID-19. A report today from the U.S. Centers for Disease Control and Prevention adds numbers and some nuance to the association.

Data from nearly 150,000 U.S. adults hospitalized with COVID-19 nationwide indicate that risk for more severe disease outcomes increases along with body mass index (BMI). The risk of COVID-19–related hospitalization and death associated with obesity was particularly high among people younger than 65.

“As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity,” the researchers note. They add that their findings suggest “progressively intensive management of COVID-19 might be needed for patients with more severe obesity.”

People with COVID-19 close to the border between a healthy and overweight BMI – from 23.7 kg/m² to 25.9 kg/m² – had the lowest risks for adverse outcomes.

The study was published online today in Morbidity and Mortality Weekly Report.
 

Greater need for critical care

The risk of ICU admission was particularly associated with severe obesity. For example, those with a BMI in the 40-44.9 kg/m² category had a 6% increased risk, which jumped to 16% higher among those with a BMI of 45 or greater.

Compared to people with a healthy BMI, the need for invasive mechanical ventilation was 12% more likely among overweight adults with a BMI of 25-29.2. The risked jumped to 108% greater among the most obese people, those with a BMI of 45 or greater, lead CDC researcher Lyudmyla Kompaniyets, PhD, and colleagues reported.

Moreover, the risks for hospitalization and death increased in a dose-response relationship with obesity.

For example, risks of being hospitalized were 7% greater for adults with a BMI between 30 and 34.9 and climbed to 33% greater for those with a BMI of 45. Risks were calculated as adjusted relative risks compared with people with a healthy BMI between 18.5 and 24.9.

Interestingly, being underweight was associated with elevated risk for COVID-19 hospitalization as well. For example, people with a BMI of less than 18.5 had a 20% greater chance of admission vs. people in the healthy BMI range. Unknown underlying medical conditions or issues related to nutrition or immune function could be contributing factors, the researchers note.
 

Elevated risk of dying

The risk of death in adults with obesity ranged from 8% higher in the 30-34.9 range up to 61% greater for those with a BMI of 45.

Chronic inflammation or impaired lung function from excess weight are possible reasons that higher BMI imparts greater risk, the researchers note.

The CDC researchers evaluated 148,494 adults from 238 hospitals participating in PHD-SR database. Because the study was limited to people hospitalized with COVID-19, the findings may not apply to all adults with COVID-19.

Another potential limitation is that investigators were unable to calculate BMI for all patients in the database because about 28% of participating hospitals did not report height and weight.

The study authors had no relevant financial relationships to disclose. 

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

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

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

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

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

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

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

A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically meaningful 5% loss in weight for roughly two-thirds of patients with both overweight/obesity and type 2 diabetes, researchers report.

These findings from the Semaglutide Treatment Effect in People With Obesity 2 (STEP 2) trial, one of four phase 3 trials of this drug, which is currently under regulatory review for weight loss, were published March 2 in The Lancet.

More than 1,000 patients (mean initial weight, 100 kg [220 pounds]) were randomly assigned to receive a lifestyle intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they had lost a mean of 9.6%, 7.0%, and 3.4%, respectively, of their starting weight.

In addition, 69% of patients who had received semaglutide 2.4 mg experienced a clinically meaningful 5% loss of weight, compared with 57% of patients who had received the lower dose and 29% of patients who had received placebo.

The higher dose of semaglutide was associated with a greater improvement in cardiometabolic risk factors. The safety profile was similar to that seen with other drugs in this class.
 

“By far the best results with any weight loss medicine in diabetes”

Importantly, “more than a quarter of participants lost over 15% of their body weight,” senior author Ildiko Lingvay, MD, stressed. This “is by far the best result we had with any weight loss medicine in patients with diabetes,” Dr. Lingvay, of the University of Texas, Dallas, said in a statement from the university.

Sara Freeman/MDedge News

“The drug works by suppressing appetite centers in the brain to reduce caloric intake,” she explained. “The medication continually tells the body that you just ate, you’re full.”

Similarly, lead author Melanie J. Davies, MD, said that the STEP 2 results “are exciting and represent a new era in weight management in people with type 2 diabetes.

Sara Freeman/MDedge News

One of four trials under review

More than 90% of people with type 2 diabetes are overweight or have obesity, and more than 20% of people with obesity have diabetes, wrote Dr. Davies and colleagues.

Semaglutide (Ozempic), administered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is approved by the Food and Drug Administration for the treatment of type 2 diabetes. Dosing studies indicated that it is associated with weight loss.

As previously reported, four trials of the use of semaglutide for weight loss (STEP 1, 2, 3, and 4) have been completed. The combined data were submitted to the FDA on Dec. 4, 2020 (a decision is expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.

The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs. placebo were recently published. The STEP 1 trial involved 1,961 adults with obesity or overweight; the STEP 3 trial, 611 adults with obesity or overweight. In each of the trials, some patients also underwent an intensive lifestyle intervention, and some did not. In both trials, patients with type 2 diabetes were excluded.

Topline results from STEP 2 were reported in June 2020.
 

STEP 2 enrolled patients with type 2 diabetes

STEP 2 involved 1,210 adults in 149 outpatient clinics in 12 countries in Europe, North America, South America, the Middle East, South Africa, and Asia. All participants had type 2 diabetes.

For all patients, the body mass index was ≥27 kg/m², and the A1c concentration was 7%-10%. The mean BMI was 35.7 kg/m², and the mean A1c was 8.1%.

The mean age of the patients was 55 years, and 51% were women; 62% were White, 26% were Asian, 13% were Hispanic, 8% were Black, and 4% were of other ethnicity.

Participants were managed with diet and exercise alone or underwent treatment with a stable dose of up to three oral glucose-lowering agents (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for at least 90 days. They were then randomly assigned in 1:1:1 ratio to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.

The starting dose of semaglutide was 0.25 mg/wk; the dose was escalated every 4 weeks to reach the target dose.

All patients received monthly counseling from a dietitian about calories (the goal was a 500-calorie/day deficit) and activity (the goal was 150 minutes of walking or stair climbing per week).

The mean A1c dropped by 1.6% and 1.5% in the semaglutide groups and by 0.4% in the placebo group.

Adverse events were more frequent among the patients who received semaglutide (88% and 82%) than in the placebo group (77%).

Gastrointestinal events that were mainly mild to moderate in severity were reported by 64% of patients in the 2.4-mg semaglutide group, 58% in the 1.0-mg semaglutide group, and 34% in the placebo group.

Semaglutide (Rybelsus) is approved in the United States as a once-daily oral agent for use in type 2 diabetes in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.

The study was supported by Novo Nordisk. The authors’ relevant financial relationships are listed in the original article.

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

A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically meaningful 5% loss in weight for roughly two-thirds of patients with both overweight/obesity and type 2 diabetes, researchers report.

These findings from the Semaglutide Treatment Effect in People With Obesity 2 (STEP 2) trial, one of four phase 3 trials of this drug, which is currently under regulatory review for weight loss, were published March 2 in The Lancet.

More than 1,000 patients (mean initial weight, 100 kg [220 pounds]) were randomly assigned to receive a lifestyle intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they had lost a mean of 9.6%, 7.0%, and 3.4%, respectively, of their starting weight.

In addition, 69% of patients who had received semaglutide 2.4 mg experienced a clinically meaningful 5% loss of weight, compared with 57% of patients who had received the lower dose and 29% of patients who had received placebo.

The higher dose of semaglutide was associated with a greater improvement in cardiometabolic risk factors. The safety profile was similar to that seen with other drugs in this class.
 

“By far the best results with any weight loss medicine in diabetes”

Importantly, “more than a quarter of participants lost over 15% of their body weight,” senior author Ildiko Lingvay, MD, stressed. This “is by far the best result we had with any weight loss medicine in patients with diabetes,” Dr. Lingvay, of the University of Texas, Dallas, said in a statement from the university.

Sara Freeman/MDedge News

“The drug works by suppressing appetite centers in the brain to reduce caloric intake,” she explained. “The medication continually tells the body that you just ate, you’re full.”

Similarly, lead author Melanie J. Davies, MD, said that the STEP 2 results “are exciting and represent a new era in weight management in people with type 2 diabetes.

Sara Freeman/MDedge News

One of four trials under review

More than 90% of people with type 2 diabetes are overweight or have obesity, and more than 20% of people with obesity have diabetes, wrote Dr. Davies and colleagues.

Semaglutide (Ozempic), administered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is approved by the Food and Drug Administration for the treatment of type 2 diabetes. Dosing studies indicated that it is associated with weight loss.

As previously reported, four trials of the use of semaglutide for weight loss (STEP 1, 2, 3, and 4) have been completed. The combined data were submitted to the FDA on Dec. 4, 2020 (a decision is expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.

The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs. placebo were recently published. The STEP 1 trial involved 1,961 adults with obesity or overweight; the STEP 3 trial, 611 adults with obesity or overweight. In each of the trials, some patients also underwent an intensive lifestyle intervention, and some did not. In both trials, patients with type 2 diabetes were excluded.

Topline results from STEP 2 were reported in June 2020.
 

STEP 2 enrolled patients with type 2 diabetes

STEP 2 involved 1,210 adults in 149 outpatient clinics in 12 countries in Europe, North America, South America, the Middle East, South Africa, and Asia. All participants had type 2 diabetes.

For all patients, the body mass index was ≥27 kg/m², and the A1c concentration was 7%-10%. The mean BMI was 35.7 kg/m², and the mean A1c was 8.1%.

The mean age of the patients was 55 years, and 51% were women; 62% were White, 26% were Asian, 13% were Hispanic, 8% were Black, and 4% were of other ethnicity.

Participants were managed with diet and exercise alone or underwent treatment with a stable dose of up to three oral glucose-lowering agents (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for at least 90 days. They were then randomly assigned in 1:1:1 ratio to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.

The starting dose of semaglutide was 0.25 mg/wk; the dose was escalated every 4 weeks to reach the target dose.

All patients received monthly counseling from a dietitian about calories (the goal was a 500-calorie/day deficit) and activity (the goal was 150 minutes of walking or stair climbing per week).

The mean A1c dropped by 1.6% and 1.5% in the semaglutide groups and by 0.4% in the placebo group.

Adverse events were more frequent among the patients who received semaglutide (88% and 82%) than in the placebo group (77%).

Gastrointestinal events that were mainly mild to moderate in severity were reported by 64% of patients in the 2.4-mg semaglutide group, 58% in the 1.0-mg semaglutide group, and 34% in the placebo group.

Semaglutide (Rybelsus) is approved in the United States as a once-daily oral agent for use in type 2 diabetes in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.

The study was supported by Novo Nordisk. The authors’ relevant financial relationships are listed in the original article.

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

A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically meaningful 5% loss in weight for roughly two-thirds of patients with both overweight/obesity and type 2 diabetes, researchers report.

These findings from the Semaglutide Treatment Effect in People With Obesity 2 (STEP 2) trial, one of four phase 3 trials of this drug, which is currently under regulatory review for weight loss, were published March 2 in The Lancet.

More than 1,000 patients (mean initial weight, 100 kg [220 pounds]) were randomly assigned to receive a lifestyle intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they had lost a mean of 9.6%, 7.0%, and 3.4%, respectively, of their starting weight.

In addition, 69% of patients who had received semaglutide 2.4 mg experienced a clinically meaningful 5% loss of weight, compared with 57% of patients who had received the lower dose and 29% of patients who had received placebo.

The higher dose of semaglutide was associated with a greater improvement in cardiometabolic risk factors. The safety profile was similar to that seen with other drugs in this class.
 

“By far the best results with any weight loss medicine in diabetes”

Importantly, “more than a quarter of participants lost over 15% of their body weight,” senior author Ildiko Lingvay, MD, stressed. This “is by far the best result we had with any weight loss medicine in patients with diabetes,” Dr. Lingvay, of the University of Texas, Dallas, said in a statement from the university.

Sara Freeman/MDedge News

“The drug works by suppressing appetite centers in the brain to reduce caloric intake,” she explained. “The medication continually tells the body that you just ate, you’re full.”

Similarly, lead author Melanie J. Davies, MD, said that the STEP 2 results “are exciting and represent a new era in weight management in people with type 2 diabetes.

Sara Freeman/MDedge News

One of four trials under review

More than 90% of people with type 2 diabetes are overweight or have obesity, and more than 20% of people with obesity have diabetes, wrote Dr. Davies and colleagues.

Semaglutide (Ozempic), administered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is approved by the Food and Drug Administration for the treatment of type 2 diabetes. Dosing studies indicated that it is associated with weight loss.

As previously reported, four trials of the use of semaglutide for weight loss (STEP 1, 2, 3, and 4) have been completed. The combined data were submitted to the FDA on Dec. 4, 2020 (a decision is expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.

The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs. placebo were recently published. The STEP 1 trial involved 1,961 adults with obesity or overweight; the STEP 3 trial, 611 adults with obesity or overweight. In each of the trials, some patients also underwent an intensive lifestyle intervention, and some did not. In both trials, patients with type 2 diabetes were excluded.

Topline results from STEP 2 were reported in June 2020.
 

STEP 2 enrolled patients with type 2 diabetes

STEP 2 involved 1,210 adults in 149 outpatient clinics in 12 countries in Europe, North America, South America, the Middle East, South Africa, and Asia. All participants had type 2 diabetes.

For all patients, the body mass index was ≥27 kg/m², and the A1c concentration was 7%-10%. The mean BMI was 35.7 kg/m², and the mean A1c was 8.1%.

The mean age of the patients was 55 years, and 51% were women; 62% were White, 26% were Asian, 13% were Hispanic, 8% were Black, and 4% were of other ethnicity.

Participants were managed with diet and exercise alone or underwent treatment with a stable dose of up to three oral glucose-lowering agents (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for at least 90 days. They were then randomly assigned in 1:1:1 ratio to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.

The starting dose of semaglutide was 0.25 mg/wk; the dose was escalated every 4 weeks to reach the target dose.

All patients received monthly counseling from a dietitian about calories (the goal was a 500-calorie/day deficit) and activity (the goal was 150 minutes of walking or stair climbing per week).

The mean A1c dropped by 1.6% and 1.5% in the semaglutide groups and by 0.4% in the placebo group.

Adverse events were more frequent among the patients who received semaglutide (88% and 82%) than in the placebo group (77%).

Gastrointestinal events that were mainly mild to moderate in severity were reported by 64% of patients in the 2.4-mg semaglutide group, 58% in the 1.0-mg semaglutide group, and 34% in the placebo group.

Semaglutide (Rybelsus) is approved in the United States as a once-daily oral agent for use in type 2 diabetes in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.

The study was supported by Novo Nordisk. The authors’ relevant financial relationships are listed in the original article.

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

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

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

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

DOACs discouraged in patients with mechanical or bioprosthetic valves

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

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

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

Registry shows trends in prescribing

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

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

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

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

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

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

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

Expert: One percent is ‘very small number’

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

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

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

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

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

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

DOACs discouraged in patients with mechanical or bioprosthetic valves

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

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

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

Registry shows trends in prescribing

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

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

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

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

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

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

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

Expert: One percent is ‘very small number’

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

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

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

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

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

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

DOACs discouraged in patients with mechanical or bioprosthetic valves

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

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

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

Registry shows trends in prescribing

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

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

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

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

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

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

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

Expert: One percent is ‘very small number’

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

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

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

The discovery of any novel disease or condition means a steep learning curve as physicians must develop protocols for diagnosis, management, and follow-up on the fly in the midst of admitting and treating patients. Medical society task forces and committees often release interim guidance during the learning process, but each institution ultimately has to determine what works for them based on their resources, clinical experience, and patient population.

Geber86/Getty Images

But when the novel condition demands the involvement of multiple different specialties, the challenge of management grows even more complex – as does follow-up after patients are discharged. Such has been the story with multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19 that shares some features with Kawasaki disease.

The similarities to Kawasaki provided physicians a place to start in developing appropriate treatment regimens and involved a similar interdisciplinary team from, at the least, cardiology and rheumatology, plus infectious disease since MIS-C results from COVID-19.

“It literally has it in the name – multisystem essentially hints that there are multiple specialties involved, multiple hands in the pot trying to manage the kids, and so each specialty has their own kind of unique role in the patient’s care even on the outpatient side,” said Samina S. Bhumbra, MD, an infectious disease pediatrician at Riley Hospital for Children and assistant professor of clinical pediatrics at Indiana University in Indianapolis. “This isn’t a disease that falls under one specialty.”

Determining a follow-up regimen

Even before determining how to coordinate appointments, hospitals had to decide what follow-up itself should be.

“How long do we follow these patients and how often do we follow them?” said Melissa S. Oliver, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University.

“We’re seeing that a lot of our patients rapidly respond when they get appropriate therapy, but we don’t know about long-term outcomes yet. We’re all still learning.”

At Children’s Hospital of Philadelphia, infectious disease follows up 4-6 weeks post discharge. The cardiology division came up with a follow-up plan that has evolved over time, said Matthew Elias, MD, an attending cardiologist at CHOP’s Cardiac Center and clinical assistant professor of pediatrics at the University of Pennsylvania, Philadelphia.

The dedicated clinic model

The two challenges Riley needed to address were the lack of a clear consensus on what MIS-C follow-up should look like and the need for continuity of care, Dr. Serrano said.

Regular discussion in departmental meetings at Riley “progressed from how do we take care of them and what treatments do we give them to how do we follow them and manage them in outpatient,” Dr. Oliver said. In the inpatient setting, they had an interdisciplinary team, but how could they maintain that for outpatients without overwhelming the families?

“I think the main challenge is for the families to identify who is leading the care for them,” said Martha M. Rodriguez, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University. That sometimes led to families picking which follow-up appointments they would attend and which they would skip if they could not make them all – and sometimes they skipped the more important ones. “They would go to the appointment with me and then miss the cardiology appointments and the echocardiogram, which was more important to follow any abnormalities in the heart,” Dr. Rodriguez said.

After trying to coordinate separate follow-up appointments for months, Riley ultimately decided to form a dedicated clinic for MIS-C follow-up – a “one-stop shop” single appointment at each follow-up, Dr. Bhumbra said, that covers labs, EKG, echocardiogram, and any other necessary tests.

“Our goal with the clinic is to make life easier for the families and to be able to coordinate the appointments,” Dr. Rodriguez said. “They will be able to see the three of us, and it would be easier for us to communicate with each other about their plan.”

The clinic began Feb. 11 and occurs twice a month. Though it’s just begun, Dr. Oliver said the first clinic went well, and it’s helping them figure out the role each specialty needs to play in follow-up care.

“For us with rheumatology, after lab values have returned to normal and they’re off steroids, sometimes we think there isn’t much more we can contribute to,” she said. And then there are the patients who didn’t see any rheumatologists while inpatients.

“That’s what we’re trying to figure out as well,” Dr. Oliver said. “Should we be seeing every single kid regardless of whether we were involved in their inpatient [stay] or only seeing the ones we’ve seen?” She expects the coming months will help them work that out.

Texas Children’s Hospital in Houston also uses a dedicated clinic, but they set it up before the first MIS-C patient came through the doors, said Sara Kristen Sexson Tejtel, MD, a pediatric cardiologist at Texas Children’s. The hospital already has other types of multidisciplinary clinics, and they anticipated the challenge of getting families to come to too many appointments in a short period of time.

Separate but coordinated appointments

A dedicated clinic isn’t the answer for all institutions, however. At Children’s Hospital of Philadelphia, the size of the networks and all its satellites made a one-stop shop impractical.

“We talked about a consolidated clinic early on, when MIS-C was first emerging and all our groups were collaborating and coming up with our inpatient and outpatient care pathways,” said Sanjeev K. Swami, MD, an infectious disease pediatrician at CHOP and associate professor of clinical pediatrics at the University of Pennsylvania. But timing varies on when each specialist wants to see the families return, and existing clinic schedules and locations varied too much.

Looking ahead

The biggest question that still looms is what happens to these children, if anything, down the line.

“What was unique about this was this was a new disease we were all learning about together with no baseline,” Dr. Swami said. “None of us had ever seen this condition before.”

So far, the prognosis for the vast majority of children is good. “Most of these kids survive, most of them are doing well, and they almost all recover,” Dr. Serrano said. Labs tend to normalize by 6 weeks post discharge, if not much earlier, and not much cardiac involvement is showing up at later follow-ups. But not even a year has passed, so there’s plenty to learn. “We don’t know if there’s long-term risk. I would not be surprised if 20 years down the road we’re finding out things about this that we had no idea” about, Dr. Serrano said. “Everybody wants answers, and nobody has any, and the answers we have may end up being wrong. That’s how it goes when you’re dealing with something you’ve never seen.”

Research underway will ideally begin providing those answers soon. CHOP is a participating site in an NIH-NHLBI–sponsored study, called COVID MUSIC, that is tracking long-term outcomes for MIS-C at 30 centers across the United States and Canada for 5 years.

“That will really definitely be helpful in answering some of the questions about long-term outcomes,” Dr. Elias said. “We hope this is going to be a transient issue and that patients won’t have any long-term manifestations, but we don’t know that yet.”

Meanwhile, one benefit that has come out of the pandemic is strong collaboration, Dr. Bhumbra said.

“The biggest thing we’re all eagerly waiting and hoping for is standard guidelines on how best to follow-up on these kids, but I know that’s a ways away,” Dr. Bhumbra said. So for now, each institution is doing what it can to develop protocols that they feel best serve the patients’ needs, such as Riley’s new dedicated MIS-C clinic. “It takes a village to take care of these kids, and MIS-C has proven that having a clinic with all three specialties at one clinic is going to be great for the families.”

Dr. Fox serves on a committee for Pfizer unrelated to MIS-C. No other doctors interviewed for this story had relevant conflicts of interest to disclose.

The discovery of any novel disease or condition means a steep learning curve as physicians must develop protocols for diagnosis, management, and follow-up on the fly in the midst of admitting and treating patients. Medical society task forces and committees often release interim guidance during the learning process, but each institution ultimately has to determine what works for them based on their resources, clinical experience, and patient population.

Geber86/Getty Images

But when the novel condition demands the involvement of multiple different specialties, the challenge of management grows even more complex – as does follow-up after patients are discharged. Such has been the story with multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19 that shares some features with Kawasaki disease.

The similarities to Kawasaki provided physicians a place to start in developing appropriate treatment regimens and involved a similar interdisciplinary team from, at the least, cardiology and rheumatology, plus infectious disease since MIS-C results from COVID-19.

“It literally has it in the name – multisystem essentially hints that there are multiple specialties involved, multiple hands in the pot trying to manage the kids, and so each specialty has their own kind of unique role in the patient’s care even on the outpatient side,” said Samina S. Bhumbra, MD, an infectious disease pediatrician at Riley Hospital for Children and assistant professor of clinical pediatrics at Indiana University in Indianapolis. “This isn’t a disease that falls under one specialty.”

Determining a follow-up regimen

Even before determining how to coordinate appointments, hospitals had to decide what follow-up itself should be.

“How long do we follow these patients and how often do we follow them?” said Melissa S. Oliver, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University.

“We’re seeing that a lot of our patients rapidly respond when they get appropriate therapy, but we don’t know about long-term outcomes yet. We’re all still learning.”

At Children’s Hospital of Philadelphia, infectious disease follows up 4-6 weeks post discharge. The cardiology division came up with a follow-up plan that has evolved over time, said Matthew Elias, MD, an attending cardiologist at CHOP’s Cardiac Center and clinical assistant professor of pediatrics at the University of Pennsylvania, Philadelphia.

The dedicated clinic model

The two challenges Riley needed to address were the lack of a clear consensus on what MIS-C follow-up should look like and the need for continuity of care, Dr. Serrano said.

Regular discussion in departmental meetings at Riley “progressed from how do we take care of them and what treatments do we give them to how do we follow them and manage them in outpatient,” Dr. Oliver said. In the inpatient setting, they had an interdisciplinary team, but how could they maintain that for outpatients without overwhelming the families?

“I think the main challenge is for the families to identify who is leading the care for them,” said Martha M. Rodriguez, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University. That sometimes led to families picking which follow-up appointments they would attend and which they would skip if they could not make them all – and sometimes they skipped the more important ones. “They would go to the appointment with me and then miss the cardiology appointments and the echocardiogram, which was more important to follow any abnormalities in the heart,” Dr. Rodriguez said.

After trying to coordinate separate follow-up appointments for months, Riley ultimately decided to form a dedicated clinic for MIS-C follow-up – a “one-stop shop” single appointment at each follow-up, Dr. Bhumbra said, that covers labs, EKG, echocardiogram, and any other necessary tests.

“Our goal with the clinic is to make life easier for the families and to be able to coordinate the appointments,” Dr. Rodriguez said. “They will be able to see the three of us, and it would be easier for us to communicate with each other about their plan.”

The clinic began Feb. 11 and occurs twice a month. Though it’s just begun, Dr. Oliver said the first clinic went well, and it’s helping them figure out the role each specialty needs to play in follow-up care.

“For us with rheumatology, after lab values have returned to normal and they’re off steroids, sometimes we think there isn’t much more we can contribute to,” she said. And then there are the patients who didn’t see any rheumatologists while inpatients.

“That’s what we’re trying to figure out as well,” Dr. Oliver said. “Should we be seeing every single kid regardless of whether we were involved in their inpatient [stay] or only seeing the ones we’ve seen?” She expects the coming months will help them work that out.

Texas Children’s Hospital in Houston also uses a dedicated clinic, but they set it up before the first MIS-C patient came through the doors, said Sara Kristen Sexson Tejtel, MD, a pediatric cardiologist at Texas Children’s. The hospital already has other types of multidisciplinary clinics, and they anticipated the challenge of getting families to come to too many appointments in a short period of time.

Separate but coordinated appointments

A dedicated clinic isn’t the answer for all institutions, however. At Children’s Hospital of Philadelphia, the size of the networks and all its satellites made a one-stop shop impractical.

“We talked about a consolidated clinic early on, when MIS-C was first emerging and all our groups were collaborating and coming up with our inpatient and outpatient care pathways,” said Sanjeev K. Swami, MD, an infectious disease pediatrician at CHOP and associate professor of clinical pediatrics at the University of Pennsylvania. But timing varies on when each specialist wants to see the families return, and existing clinic schedules and locations varied too much.

Looking ahead

The biggest question that still looms is what happens to these children, if anything, down the line.

“What was unique about this was this was a new disease we were all learning about together with no baseline,” Dr. Swami said. “None of us had ever seen this condition before.”

So far, the prognosis for the vast majority of children is good. “Most of these kids survive, most of them are doing well, and they almost all recover,” Dr. Serrano said. Labs tend to normalize by 6 weeks post discharge, if not much earlier, and not much cardiac involvement is showing up at later follow-ups. But not even a year has passed, so there’s plenty to learn. “We don’t know if there’s long-term risk. I would not be surprised if 20 years down the road we’re finding out things about this that we had no idea” about, Dr. Serrano said. “Everybody wants answers, and nobody has any, and the answers we have may end up being wrong. That’s how it goes when you’re dealing with something you’ve never seen.”

Research underway will ideally begin providing those answers soon. CHOP is a participating site in an NIH-NHLBI–sponsored study, called COVID MUSIC, that is tracking long-term outcomes for MIS-C at 30 centers across the United States and Canada for 5 years.

“That will really definitely be helpful in answering some of the questions about long-term outcomes,” Dr. Elias said. “We hope this is going to be a transient issue and that patients won’t have any long-term manifestations, but we don’t know that yet.”

Meanwhile, one benefit that has come out of the pandemic is strong collaboration, Dr. Bhumbra said.

“The biggest thing we’re all eagerly waiting and hoping for is standard guidelines on how best to follow-up on these kids, but I know that’s a ways away,” Dr. Bhumbra said. So for now, each institution is doing what it can to develop protocols that they feel best serve the patients’ needs, such as Riley’s new dedicated MIS-C clinic. “It takes a village to take care of these kids, and MIS-C has proven that having a clinic with all three specialties at one clinic is going to be great for the families.”

Dr. Fox serves on a committee for Pfizer unrelated to MIS-C. No other doctors interviewed for this story had relevant conflicts of interest to disclose.

The discovery of any novel disease or condition means a steep learning curve as physicians must develop protocols for diagnosis, management, and follow-up on the fly in the midst of admitting and treating patients. Medical society task forces and committees often release interim guidance during the learning process, but each institution ultimately has to determine what works for them based on their resources, clinical experience, and patient population.

Geber86/Getty Images

But when the novel condition demands the involvement of multiple different specialties, the challenge of management grows even more complex – as does follow-up after patients are discharged. Such has been the story with multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19 that shares some features with Kawasaki disease.

The similarities to Kawasaki provided physicians a place to start in developing appropriate treatment regimens and involved a similar interdisciplinary team from, at the least, cardiology and rheumatology, plus infectious disease since MIS-C results from COVID-19.

“It literally has it in the name – multisystem essentially hints that there are multiple specialties involved, multiple hands in the pot trying to manage the kids, and so each specialty has their own kind of unique role in the patient’s care even on the outpatient side,” said Samina S. Bhumbra, MD, an infectious disease pediatrician at Riley Hospital for Children and assistant professor of clinical pediatrics at Indiana University in Indianapolis. “This isn’t a disease that falls under one specialty.”

Determining a follow-up regimen

Even before determining how to coordinate appointments, hospitals had to decide what follow-up itself should be.

“How long do we follow these patients and how often do we follow them?” said Melissa S. Oliver, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University.

“We’re seeing that a lot of our patients rapidly respond when they get appropriate therapy, but we don’t know about long-term outcomes yet. We’re all still learning.”

At Children’s Hospital of Philadelphia, infectious disease follows up 4-6 weeks post discharge. The cardiology division came up with a follow-up plan that has evolved over time, said Matthew Elias, MD, an attending cardiologist at CHOP’s Cardiac Center and clinical assistant professor of pediatrics at the University of Pennsylvania, Philadelphia.

The dedicated clinic model

The two challenges Riley needed to address were the lack of a clear consensus on what MIS-C follow-up should look like and the need for continuity of care, Dr. Serrano said.

Regular discussion in departmental meetings at Riley “progressed from how do we take care of them and what treatments do we give them to how do we follow them and manage them in outpatient,” Dr. Oliver said. In the inpatient setting, they had an interdisciplinary team, but how could they maintain that for outpatients without overwhelming the families?

“I think the main challenge is for the families to identify who is leading the care for them,” said Martha M. Rodriguez, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University. That sometimes led to families picking which follow-up appointments they would attend and which they would skip if they could not make them all – and sometimes they skipped the more important ones. “They would go to the appointment with me and then miss the cardiology appointments and the echocardiogram, which was more important to follow any abnormalities in the heart,” Dr. Rodriguez said.

After trying to coordinate separate follow-up appointments for months, Riley ultimately decided to form a dedicated clinic for MIS-C follow-up – a “one-stop shop” single appointment at each follow-up, Dr. Bhumbra said, that covers labs, EKG, echocardiogram, and any other necessary tests.

“Our goal with the clinic is to make life easier for the families and to be able to coordinate the appointments,” Dr. Rodriguez said. “They will be able to see the three of us, and it would be easier for us to communicate with each other about their plan.”

The clinic began Feb. 11 and occurs twice a month. Though it’s just begun, Dr. Oliver said the first clinic went well, and it’s helping them figure out the role each specialty needs to play in follow-up care.

“For us with rheumatology, after lab values have returned to normal and they’re off steroids, sometimes we think there isn’t much more we can contribute to,” she said. And then there are the patients who didn’t see any rheumatologists while inpatients.

“That’s what we’re trying to figure out as well,” Dr. Oliver said. “Should we be seeing every single kid regardless of whether we were involved in their inpatient [stay] or only seeing the ones we’ve seen?” She expects the coming months will help them work that out.

Texas Children’s Hospital in Houston also uses a dedicated clinic, but they set it up before the first MIS-C patient came through the doors, said Sara Kristen Sexson Tejtel, MD, a pediatric cardiologist at Texas Children’s. The hospital already has other types of multidisciplinary clinics, and they anticipated the challenge of getting families to come to too many appointments in a short period of time.

Separate but coordinated appointments

A dedicated clinic isn’t the answer for all institutions, however. At Children’s Hospital of Philadelphia, the size of the networks and all its satellites made a one-stop shop impractical.

“We talked about a consolidated clinic early on, when MIS-C was first emerging and all our groups were collaborating and coming up with our inpatient and outpatient care pathways,” said Sanjeev K. Swami, MD, an infectious disease pediatrician at CHOP and associate professor of clinical pediatrics at the University of Pennsylvania. But timing varies on when each specialist wants to see the families return, and existing clinic schedules and locations varied too much.

Looking ahead

The biggest question that still looms is what happens to these children, if anything, down the line.

“What was unique about this was this was a new disease we were all learning about together with no baseline,” Dr. Swami said. “None of us had ever seen this condition before.”

So far, the prognosis for the vast majority of children is good. “Most of these kids survive, most of them are doing well, and they almost all recover,” Dr. Serrano said. Labs tend to normalize by 6 weeks post discharge, if not much earlier, and not much cardiac involvement is showing up at later follow-ups. But not even a year has passed, so there’s plenty to learn. “We don’t know if there’s long-term risk. I would not be surprised if 20 years down the road we’re finding out things about this that we had no idea” about, Dr. Serrano said. “Everybody wants answers, and nobody has any, and the answers we have may end up being wrong. That’s how it goes when you’re dealing with something you’ve never seen.”

Research underway will ideally begin providing those answers soon. CHOP is a participating site in an NIH-NHLBI–sponsored study, called COVID MUSIC, that is tracking long-term outcomes for MIS-C at 30 centers across the United States and Canada for 5 years.

“That will really definitely be helpful in answering some of the questions about long-term outcomes,” Dr. Elias said. “We hope this is going to be a transient issue and that patients won’t have any long-term manifestations, but we don’t know that yet.”

Meanwhile, one benefit that has come out of the pandemic is strong collaboration, Dr. Bhumbra said.

“The biggest thing we’re all eagerly waiting and hoping for is standard guidelines on how best to follow-up on these kids, but I know that’s a ways away,” Dr. Bhumbra said. So for now, each institution is doing what it can to develop protocols that they feel best serve the patients’ needs, such as Riley’s new dedicated MIS-C clinic. “It takes a village to take care of these kids, and MIS-C has proven that having a clinic with all three specialties at one clinic is going to be great for the families.”

Dr. Fox serves on a committee for Pfizer unrelated to MIS-C. No other doctors interviewed for this story had relevant conflicts of interest to disclose.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

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

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

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

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

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

A 49-year-old woman with a history of end-stage renal disease, uncontrolled type 2 diabetes, and congestive heart failure visited the hospital for an acute heart failure exacerbation secondary to missed dialysis appointments. On admission, her provider noted that she had tender, pruritic lesions on the extensor surface of her arms. She said they had appeared 2 to 3 months after she started dialysis. She had attempted to control the pain and pruritus with over-the-counter topical hydrocortisone and oral diphenhydramine but nothing provided relief. She was recommended for follow-up at the hospital for further examination and biopsy of one of her lesions.

At this follow-up visit, the patient noted that the lesions had spread to her left knee. Multiple firm discrete papules and nodules, with central hyperkeratotic plugs, were noted along the extensor surfaces of her forearms, left extensor knee, and around her ankles (FIGURES 1A and 1B). Some of the lesions were tender. Examination of the rest of her skin was normal. A punch biopsy was obtained.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Kyrle disease

The patient’s end-stage renal disease and type 2 diabetes—along with findings from the physical examination—led us to suspect Kyrle disease. The punch biopsy, as well as the characteristic keratotic plugs (FIGURE 2) within epidermal invagination that was bordered by hyperkeratotic epidermis, confirmed the diagnosis.

The acquired form of Kyrle disease is associated with diabetes and renal failure, but there is a lack of data on its pathogenesis.

Kyrle disease (also known as hyperkeratosis follicularis et follicularis in cutem penetrans) is a rare skin condition. It is 1 of 4 skin conditions that are classified as perforating skin disorders; the other 3 are elastosis perforans serpiginosa, reactive perforating collagenosis, and perforating folliculitis (TABLE^1,2).³ Perforating skin disorders share the common characteristic of transepidermal elimination of material from the upper dermis.⁴ These disorders are typically classified based on the nature of the eliminated material and the type of epidermal disruption.⁵

There are 2 forms of Kyrle disease: an inherited form often seen in childhood that is not associated with systemic disease and an acquired form that occurs in adulthood, most commonly among women ages 35 to 70 years who have systemic disease.^3,4,6 The acquired form of Kyrle disease is associated with diabetes and renal failure, but there is a lack of data on its pathogenesis.^7,8

Characteristic findings include discrete pruritic, dry papules and nodules with central keratotic plugs that are occasionally tender. These can manifest over the extensor surface of the extremities, trunk, face, and scalp.^4,7,9 Lesions most commonly manifest on the extensor surfaces of the lower extremities.

Other conditions that feature pruritic lesions

In addition to the other perforating skin disorders described in the TABLE,^1,2 the differential for Kyrle disease includes the following:

Prurigo nodularis (PN) is a skin disorder in which the manifestation of extremely pruritic nodules leads to vigorous scratching and secondary infections. These lesions typically have a grouped and symmetrically distributed appearance. They often appear on extensor surfaces of upper and lower extremities.¹⁰ PN has no known etiology, but like Kyrle disease, is associated with renal failure. Biopsy can help to distinguish PN from Kyrle disease.

Continue to: Hypertrophic lichen planus

Hypertrophic lichen planus is a pruritic skin disorder characterized by the “6 Ps”: planar, purple, polygonal, pruritic, papules, and plaques. These lesions can mimic the early stages of Kyrle disease.¹¹ However, in the later stages of Kyrle disease, discrete papules with hyperkeratotic plugs develop, whereas large plaques will be seen with lichen planus.

Keratosis pilaris (KP) is an extremely common, yet benign, disorder in which hair follicles become keratinized.¹² KP can feature rough papules that are often described as “goosebumps” or having a sandpaper–like appearance. These papules often affect the upper arms. KP usually manifests in adolescents or young adults and tends to improve with age.¹² The lesions are typically smaller than those seen in Kyrle disease and are asymptomatic. In addition, KP is not associated with systemic disease.

Target symptoms and any underlying conditions

In patients who have an acquired form of the disease, symptoms may improve by treating the underlying condition. For instance, better control of type 2 diabetes may improve symptoms. In patients with end-stage renal disease, a renal transplant can bring complete resolution.¹³

For patients whose Kyrle disease is inherited or whose underlying condition is not easily treated, there are a number of treatment options to consider. First-line treatment includes topical keratolytics (salicylic acid and urea), topical retinoids, and ultraviolet light therapy.^5,7 Systemic retinoids, topical steroids, cryotherapy, electrosurgery, CO₂ laser surgery, and surgical excision have also been used with some success.^7,14 Oral histamines and emollients also may help to relieve the pruritus. Lesions often recur upon discontinuation of therapy.

Our patient was referred to Dermatology for ultraviolet light therapy. She was also treated with topical 12% ammonium lactate twice daily. Within a few months, she reported improvement of her symptoms.

A 49-year-old woman with a history of end-stage renal disease, uncontrolled type 2 diabetes, and congestive heart failure visited the hospital for an acute heart failure exacerbation secondary to missed dialysis appointments. On admission, her provider noted that she had tender, pruritic lesions on the extensor surface of her arms. She said they had appeared 2 to 3 months after she started dialysis. She had attempted to control the pain and pruritus with over-the-counter topical hydrocortisone and oral diphenhydramine but nothing provided relief. She was recommended for follow-up at the hospital for further examination and biopsy of one of her lesions.

At this follow-up visit, the patient noted that the lesions had spread to her left knee. Multiple firm discrete papules and nodules, with central hyperkeratotic plugs, were noted along the extensor surfaces of her forearms, left extensor knee, and around her ankles (FIGURES 1A and 1B). Some of the lesions were tender. Examination of the rest of her skin was normal. A punch biopsy was obtained.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Kyrle disease

The patient’s end-stage renal disease and type 2 diabetes—along with findings from the physical examination—led us to suspect Kyrle disease. The punch biopsy, as well as the characteristic keratotic plugs (FIGURE 2) within epidermal invagination that was bordered by hyperkeratotic epidermis, confirmed the diagnosis.

The acquired form of Kyrle disease is associated with diabetes and renal failure, but there is a lack of data on its pathogenesis.

Kyrle disease (also known as hyperkeratosis follicularis et follicularis in cutem penetrans) is a rare skin condition. It is 1 of 4 skin conditions that are classified as perforating skin disorders; the other 3 are elastosis perforans serpiginosa, reactive perforating collagenosis, and perforating folliculitis (TABLE^1,2).³ Perforating skin disorders share the common characteristic of transepidermal elimination of material from the upper dermis.⁴ These disorders are typically classified based on the nature of the eliminated material and the type of epidermal disruption.⁵

There are 2 forms of Kyrle disease: an inherited form often seen in childhood that is not associated with systemic disease and an acquired form that occurs in adulthood, most commonly among women ages 35 to 70 years who have systemic disease.^3,4,6 The acquired form of Kyrle disease is associated with diabetes and renal failure, but there is a lack of data on its pathogenesis.^7,8

Characteristic findings include discrete pruritic, dry papules and nodules with central keratotic plugs that are occasionally tender. These can manifest over the extensor surface of the extremities, trunk, face, and scalp.^4,7,9 Lesions most commonly manifest on the extensor surfaces of the lower extremities.

Other conditions that feature pruritic lesions

In addition to the other perforating skin disorders described in the TABLE,^1,2 the differential for Kyrle disease includes the following:

Prurigo nodularis (PN) is a skin disorder in which the manifestation of extremely pruritic nodules leads to vigorous scratching and secondary infections. These lesions typically have a grouped and symmetrically distributed appearance. They often appear on extensor surfaces of upper and lower extremities.¹⁰ PN has no known etiology, but like Kyrle disease, is associated with renal failure. Biopsy can help to distinguish PN from Kyrle disease.

Continue to: Hypertrophic lichen planus

Hypertrophic lichen planus is a pruritic skin disorder characterized by the “6 Ps”: planar, purple, polygonal, pruritic, papules, and plaques. These lesions can mimic the early stages of Kyrle disease.¹¹ However, in the later stages of Kyrle disease, discrete papules with hyperkeratotic plugs develop, whereas large plaques will be seen with lichen planus.

Keratosis pilaris (KP) is an extremely common, yet benign, disorder in which hair follicles become keratinized.¹² KP can feature rough papules that are often described as “goosebumps” or having a sandpaper–like appearance. These papules often affect the upper arms. KP usually manifests in adolescents or young adults and tends to improve with age.¹² The lesions are typically smaller than those seen in Kyrle disease and are asymptomatic. In addition, KP is not associated with systemic disease.

Target symptoms and any underlying conditions

In patients who have an acquired form of the disease, symptoms may improve by treating the underlying condition. For instance, better control of type 2 diabetes may improve symptoms. In patients with end-stage renal disease, a renal transplant can bring complete resolution.¹³

For patients whose Kyrle disease is inherited or whose underlying condition is not easily treated, there are a number of treatment options to consider. First-line treatment includes topical keratolytics (salicylic acid and urea), topical retinoids, and ultraviolet light therapy.^5,7 Systemic retinoids, topical steroids, cryotherapy, electrosurgery, CO₂ laser surgery, and surgical excision have also been used with some success.^7,14 Oral histamines and emollients also may help to relieve the pruritus. Lesions often recur upon discontinuation of therapy.

Our patient was referred to Dermatology for ultraviolet light therapy. She was also treated with topical 12% ammonium lactate twice daily. Within a few months, she reported improvement of her symptoms.

A 49-year-old woman with a history of end-stage renal disease, uncontrolled type 2 diabetes, and congestive heart failure visited the hospital for an acute heart failure exacerbation secondary to missed dialysis appointments. On admission, her provider noted that she had tender, pruritic lesions on the extensor surface of her arms. She said they had appeared 2 to 3 months after she started dialysis. She had attempted to control the pain and pruritus with over-the-counter topical hydrocortisone and oral diphenhydramine but nothing provided relief. She was recommended for follow-up at the hospital for further examination and biopsy of one of her lesions.

At this follow-up visit, the patient noted that the lesions had spread to her left knee. Multiple firm discrete papules and nodules, with central hyperkeratotic plugs, were noted along the extensor surfaces of her forearms, left extensor knee, and around her ankles (FIGURES 1A and 1B). Some of the lesions were tender. Examination of the rest of her skin was normal. A punch biopsy was obtained.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Kyrle disease

The patient’s end-stage renal disease and type 2 diabetes—along with findings from the physical examination—led us to suspect Kyrle disease. The punch biopsy, as well as the characteristic keratotic plugs (FIGURE 2) within epidermal invagination that was bordered by hyperkeratotic epidermis, confirmed the diagnosis.

The acquired form of Kyrle disease is associated with diabetes and renal failure, but there is a lack of data on its pathogenesis.

Kyrle disease (also known as hyperkeratosis follicularis et follicularis in cutem penetrans) is a rare skin condition. It is 1 of 4 skin conditions that are classified as perforating skin disorders; the other 3 are elastosis perforans serpiginosa, reactive perforating collagenosis, and perforating folliculitis (TABLE^1,2).³ Perforating skin disorders share the common characteristic of transepidermal elimination of material from the upper dermis.⁴ These disorders are typically classified based on the nature of the eliminated material and the type of epidermal disruption.⁵

There are 2 forms of Kyrle disease: an inherited form often seen in childhood that is not associated with systemic disease and an acquired form that occurs in adulthood, most commonly among women ages 35 to 70 years who have systemic disease.^3,4,6 The acquired form of Kyrle disease is associated with diabetes and renal failure, but there is a lack of data on its pathogenesis.^7,8

Characteristic findings include discrete pruritic, dry papules and nodules with central keratotic plugs that are occasionally tender. These can manifest over the extensor surface of the extremities, trunk, face, and scalp.^4,7,9 Lesions most commonly manifest on the extensor surfaces of the lower extremities.

Other conditions that feature pruritic lesions

In addition to the other perforating skin disorders described in the TABLE,^1,2 the differential for Kyrle disease includes the following:

Prurigo nodularis (PN) is a skin disorder in which the manifestation of extremely pruritic nodules leads to vigorous scratching and secondary infections. These lesions typically have a grouped and symmetrically distributed appearance. They often appear on extensor surfaces of upper and lower extremities.¹⁰ PN has no known etiology, but like Kyrle disease, is associated with renal failure. Biopsy can help to distinguish PN from Kyrle disease.

Continue to: Hypertrophic lichen planus

Hypertrophic lichen planus is a pruritic skin disorder characterized by the “6 Ps”: planar, purple, polygonal, pruritic, papules, and plaques. These lesions can mimic the early stages of Kyrle disease.¹¹ However, in the later stages of Kyrle disease, discrete papules with hyperkeratotic plugs develop, whereas large plaques will be seen with lichen planus.

Keratosis pilaris (KP) is an extremely common, yet benign, disorder in which hair follicles become keratinized.¹² KP can feature rough papules that are often described as “goosebumps” or having a sandpaper–like appearance. These papules often affect the upper arms. KP usually manifests in adolescents or young adults and tends to improve with age.¹² The lesions are typically smaller than those seen in Kyrle disease and are asymptomatic. In addition, KP is not associated with systemic disease.

Target symptoms and any underlying conditions

In patients who have an acquired form of the disease, symptoms may improve by treating the underlying condition. For instance, better control of type 2 diabetes may improve symptoms. In patients with end-stage renal disease, a renal transplant can bring complete resolution.¹³

For patients whose Kyrle disease is inherited or whose underlying condition is not easily treated, there are a number of treatment options to consider. First-line treatment includes topical keratolytics (salicylic acid and urea), topical retinoids, and ultraviolet light therapy.^5,7 Systemic retinoids, topical steroids, cryotherapy, electrosurgery, CO₂ laser surgery, and surgical excision have also been used with some success.^7,14 Oral histamines and emollients also may help to relieve the pruritus. Lesions often recur upon discontinuation of therapy.

Our patient was referred to Dermatology for ultraviolet light therapy. She was also treated with topical 12% ammonium lactate twice daily. Within a few months, she reported improvement of her symptoms.

Palpitations, the sensory perception of one’s heartbeat, are reported in 16% of primary care patients, from causes that are both cardiac (ie, arrhythmias) and noncardiac.¹ Palpitations are usually benign; overall mortality is approximately 1% annually. In fact, a retrospective study found no difference in mortality and morbidity between patients with palpitations and control patients without palpitations.² However, palpitations can reflect a life-threatening cardiac condition, as we discuss in this article, making careful assessment and targeted, sometimes urgent, intervention important.³

Here, we review the clinical work-up of palpitations, recommended diagnostic testing, and the range of interventions for cardiac arrhythmias—ectopic beats, ventricular tachycardia (VT), and atrial fibrillation (AF).

Cardiac and noncardiac causes of palpitations

In a prospective cohort study of 190 consecutive patients presenting with palpitations, the cause was cardiac in 43%, psychiatric in 31%, and of a miscellaneous nature (including medication, thyrotoxicosis, caffeine, cocaine, anemia, amphetamine, and mastocytosis) in 10%; in 16%, the cause was undetermined.² In this study, 77% of patients experienced a recurrence of palpitations after their first episode.²

Cardiac arrhythmias, a common cause of palpitations, are differentiated by site of origin—supraventricular and ventricular. Noncardiac causes of palpitations, which we do not discuss here, include metabolic and psychiatric conditions, medications, and substance use. (For a summary of the causes of palpitations, see TABLE 1.^2-4)

Common complaint: ectopic beats. Premature atrial contractions (PACs; also known as premature atrial beats, atrial premature complexes, and atrial premature beats) and premature ventricular contractions (PVCs; also known as ventricular premature complexes and ventricular premature beats, and also of a variety of possible causes) result in a feeling of a skipped heartbeat or a flipping sensation in the chest.

Palpitations are usually benign. But they can reflect a life-threatening cardiac condition, making careful assessment and targeted, sometimes urgent, intervention important.

The burden of PACs is independently associated with mortality, cardiovascular hospitalization, new-onset AF, and pacemaker implantation. In a multivariate analysis, a PAC burden > 76 beats/d was an independent predictor of mortality (hazard ratio [HR] = 1.4; 95% CI, 1.2-16); cardiovascular hospitalization (HR = 1.3; 95% CI, 1.1-1.5); new-onset AF (HR = 1.8; 95% CI, 1.4-2.2); and pacemaker implantation (HR = 2.8; 95% CI, 1.9-4.2). Frequent PACs can lead to cardiac remodeling, so more intense follow-up of patients with a high PAC burden might allow for early detection of AF or subclinical cardiac disease.^5,6

A burden of PVCs > 24% is associated with an increased risk of PVC-induced cardiomyopathy and heart failure. Polymorphic PVCs are more concerning than monomorphic PVCs because the former suggests the presence of more diffuse, rather than localized, myocardial injury. The presence of frequent (> 1000 beats/d) PVCs warrants evaluation and treatment for underlying structural heart disease and ischemic heart disease. Therapy directed toward underlying heart disease can reduce the frequency of PVCs.^7-9

Continue to: The diagnostic work-up

The most important goal of the evaluation of palpitations is to determine the presence, or risk, of structural heart or coronary artery disease (CAD) by means of the history, physical examination, and electrocardiography (EKG). Patients who have an increased risk of structural heart disease need further evaluation with echocardiography; those at increased risk of CAD should have stress testing.

Hemodynamically unstable patients need admission; patients who have a history of syncope with palpitations usually should be admitted for cardiac monitoring. Patients who have had a single episode of palpitations and have normal baseline results of laboratory testing and a normal EKG, and no risk factors for structural heart disease or known CAD, can usually be observed.^3,4,10 Patients with an abnormal baseline EKG, recurrent palpitations (especially tachyarrhythmia), or significant symptoms during palpitations (syncope, presyncope, dyspnea) need further evaluation with ambulatory monitoring^3,4,10 (Figure).

Take a thorough history; ask these questions

Have the patient describe the palpitations. The history should include the patient’s detailed characterization of the palpitations (sudden or gradual onset, rhythm, duration, frequency). Certain descriptions provide possible diagnostic clues:

• Palpitations lasting < 5 minutes are less likely to be of cardiac origin (likelihood ratio [LR] = 0.38; 95% CI, 0.2-0.6).⁴
• A patient who has a regular, rapid-pounding sensation in the neck has an increased probability of atrioventricular (AV) nodal reentrant tachycardia (AVNRT) (LR = 177; 95% CI, 25-1251); absence of this sensation decreases the likelihood of AVNRT (LR = 0.07; 95% CI, 0.03-0.2).⁴
• PACs and PVCs cause a sensation of a skipped heartbeat or a flipping sensation in the chest; they are not reported as a sustained rapid heartbeat.
• Patients with a supraventricular arrhythmia often report sudden onset and cessation of palpitations.
• Patients with palpitations since childhood are more likely to have supraventricular tachycardia (SVT).⁴

Elicit apparent precipitating and alleviating factors. The history should include notation of situations that appear to the patient to lead to palpitations (eg, context, positional variation). Palpitations that affect sleep (LR = 2.3; 95% CI, 1.3-3.9) and palpitations that occur at work (LR = 2.2; 95% CI, 1.3-5) increase the likelihood of a cardiac cause.⁴ Palpitations associated with sudden change in position, such as bending forward or squatting, are more likely due to AVNRT.¹¹

Patients with an abnormal baseline EKG, recurrent palpitations, or significant symptoms during palpitations need evaluation with ambulatory monitoring.

Ask about aggravating factors (eg, exercise) and relieving factors (eg, rest, performing a Valsalva maneuver). Patients with SVT are often able to have palpitations terminated with a Valsalva maneuver, such as carotid sinus massage. Palpitations and syncope during exertion can be associated with hypertrophic cardiomyopathy, congenital coronary anomalies, and ion channelopathies, and can cause sudden cardiac death in athletes (estimated incidence, 1-3/100,000 person–years¹²).

Endeavor to identify underlying cardiac disease. A comprehensive history should also evaluate for risk factors and symptoms (chest pain, dyspnea, diaphoresis, lightheadedness, syncope) of cardiac disease, such as CAD, valvular disease, cardiomyopathy, and congenital heart disease, which increase the likelihood that the presenting complaint is a cardiac arrhythmia (LR = 2; 95% CI, 1.3-3.1).⁴ A history of syncope in a patient with palpitations should prompt evaluation for structural heart disease, such as aortic stenosis or hypertrophic cardiomyopathy, in which outflow-tract obstruction impairs cardiac output and, subsequently, cerebral blood flow.

Obtain additional key information. Determine the following in taking the history:

• Is there a family history of inherited cardiac disorders or sudden cardiac death?
• What prescription and over-the-counter medications is the patient taking? How does the patient characterize his or her use/intake of recreational drugs, nicotine, caffeine, and alcohol?
• Does the patient have a history of panic disorder, which lessens concern about a cardiac cause (LR = 0.2; 95% CI, 0.07-1.01)?⁴ (Of note: A nonpsychiatric cause can coexist in such patients, and should be considered.)

Continue to: Physical examination clues, and the utility of vagal maneuvers

Physical examination clues, and the utility of vagal maneuvers

Although most patients in whom palpitations are the presenting complaint are, in fact, asymptomatic during clinical assessment, cardiovascular examination can assist in diagnosing the arrhythmia or structural heart disease:

• Resting bradycardia increases the likelihood of a clinically significant arrhythmia (LR = 3; 95% CI, 1.27-7.0).¹¹
• A murmur, such as a midsystolic click or holosystolic murmur, detected during the cardiac exam can indicate mitral valve prolapse; a holosystolic murmur, exacerbated upon performing a Valsalva maneuver, suggests hypertrophic cardiomyopathy.
• Visible neck pulsations detected during assessment of the jugular venous pressure, known as cannon atrial (cannon A) waves, reflect abnormal contraction of the right atrium against a closed tricuspid valve during AV dissociation. Cannon A waves have an LR of 2.68 (95% CI, 1.25-5.78) for predicting AVNRT.⁴

Vagal nerve stimulation. In the rare circumstance that a patient complaining of palpitations is symptomatic during assessment, several tachycardias can be detected with the use of vagal maneuvers. Interruption of the tachycardia during carotid massage suggests a tachycardia involving the AV junction (AVNRT), whereas only a temporary pause or reduction in frequency is more common in atrial flutter, AF, and atrial tachycardias. Carotid massage has no effect on the presentation of ventricular arrhythmias.¹⁰

Diagnostic testing and the role of ambulatory monitoring

Electrocardiography. All patients with palpitations should have a 12-lead EKG, which may provide diagnostic clues (TABLE 2¹⁰).

Ambulatory monitoring. When the EKG is nondiagnostic, ambulatory cardiac monitoring has an established role in the diagnosis of recurrent palpitations. In a small study of patients presenting with palpitations to a general practitioner, the deduction of those practitioners was wrong more than half the time when they predicted a ≤ 20% chance of an arrhythmia based on the history, physical exam, and EKG alone¹³—emphasizing the importance of ambulatory monitoring in patients with recurrent palpitations.

A comprehensive history should also evaluate for risk factors and symptoms of cardiac disease (chest pain, dyspnea, diaphoresis, lightheadedness, syncope).

Which monitoring system is most suitable depends on symptom frequency, availability, cost, and patient competence. Twenty-four- to 48-hour Holter monitoring can be used in cases of frequent (eg, daily) palpitations. An automatic external loop recorder can be used for less frequent (eg, every 30 days) symptoms. Most ambulatory EKG is now automatic, and therefore does not require patient activation; older manual systems require patient activation during symptoms.

Two weeks of ambulatory EKG have proved sufficient for determining that there is a cardiac basis to palpitations. The diagnostic yield of ambulatory EKG is highest during Week 1 (1.04 diagnoses per patient), compared to Week 3 (0.17 diagnoses per patient).¹⁴

Implantable loop recorders are placed subcutaneously to provide EKG monitoring for approximately 3 years. They are better suited for diagnosing infrequent palpitations. The diagnostic yield of an implantable loop recorder over the course of 1 year for the detection of an arrhythmia is 73%, compared to 21% for a 24-hour Holter monitor, electrophysiology studies, and 4 weeks of an external loop recorder.¹⁵ Implantable loop recorders are often reserved for patients with palpitations associated with unexplained recurrent syncope.¹⁵

Continue to: Lab work

Lab work. A comprehensive metabolic panel, complete blood count, lipid panel, and thyroid panel should be ordered for all patients with palpitations. Possible additional tests include a urine drug screen (when recreational drug use is suspected); cardiac enzymes; N-terminal-pro hormone B-type natriuretic peptide (when there is evidence of CAD or heart failure); and urinary catecholamines (when pheochromocytoma is suspected).

Other investigations. Echocardiography is indicated when structural heart disease is suspected (TABLE 1^2-4). Patients who have multiple risk factors for CAD or exertional symptoms might warrant a stress test.

Management

PACs and PVCs

Typically, patients are counseled to minimize potential adrenergic precipitants, such as smoking, alcohol, stress, and caffeine. However, limited studies have demonstrated no significant arrhythmogenic potential of a modest dose of caffeine (200 mg), even in patients with known life-threatening ventricular arrhythmias.¹⁶ Beta-blockers and nondihydropyridine calcium channel blockers (CCBs) can reduce the severity of symptoms related to premature ectopic beats and might reduce their frequency, although response is inconsistent. Use of these medications for PACs is largely based on expert opinion and extrapolated from use in other supraventricular and ventricular arrhythmias.

Implantable cardioverter defibrillator therapy is indicated in patients with nonsustained VT due to prior myocardial infarction, left ventricular ejection fraction ≤ 40%, and inducible ventricular fibrillation or sustained VT on electrophysiological study.⁷

Patients with a high burden of ectopy who do not respond to treatment with AV nodal-blocking agents should be referred to Cardiology for other antiarrhythmic agents or catheter ablation. Last, asymptomatic ectopy does not need to be treated; there is no clear evidence that suppression with pharmacotherapy improves overall survival.^15,17

Supraventricular tachycardia

The priority when evaluating any tachycardia is to assess the patient’s stability. Unstable patients should be treated immediately, usually with cardioversion, before an extensive diagnostic evaluation.¹⁸ Patients with wide-complex tachycardia (QRS > 120 ms) are generally more unstable and require more urgent therapy and cardiac consultation or referral. Hemodynamically stable patients with narrow-complex SVT (QRS < 120 ms) can be treated with IV adenosine, which has an 89.7% success rate.^18,19 If adenosine is unsuccessful, cardioversion is indicated.

Stable patients with minimal symptoms and short episodes do not need treatment.

Continue to: Vagal maneuvers

Vagal maneuvers (eg, Valsalva maneuver; unilateral carotid massage after exclusion of a carotid bruit, with head tilted to the side opposite the massage, and not for longer than 10 seconds; or applying an ice-cold wet towel to the face) have a success rate of about 25% and are most effective when performed shortly after onset of arrhythmia. Vagal maneuvers can be used in all patients while preparing to administer medications.²⁰

Patients who need treatment can take the “pill-in-the-pocket” approach with single-dose oral flecainide (3 mg/kg) or combined diltiazem and propranolol. Flecainide has a 94% success rate; diltiazem–propranolol has a lower success rate (61%) but a shorter time to conversion to sinus rhythm.²¹ Patients with sustained or recurrent episodes of SVT should be referred to a cardiologist for chronic prophylactic drug therapy or radiofrequency ablation.

Atrial fibrillation

Hemodynamically unstable patients with AF or atrial flutter, defined by the presence of angina, decompensated heart failure, hypotension, pulmonary edema, or evidence of organ hypoperfusion, should be electrically cardioverted using synchronized direct current.

Hemodynamically stable patients with a rapid ventricular rate should be treated with an IV or oral beta-blocker, CCB, or amiodarone, or electrically cardioverted. IV medications are typically preferred in the acute setting for ease and rapidity of administration; however, there is no evidence that IV formulations of beta-blockers and CCBs are superior to oral formulations. Once the ventricular rate is controlled, patients can be transitioned to an oral short-acting preparation of the selected agent, then converted to an appropriate dosage of an extended-­release preparation.²²

Cardioversion can be performed in patients with AF < 48 hours. In patients with AF > 48 hours, either 4 weeks of anticoagulation can be given, followed by cardioversion, or transesophageal echocardiography should be performed to evaluate for atrial thrombus; if atrial thrombus is absent, cardioversion can be performed.²² Transesophageal echocardiography might be unnecessary in patients known to have been on sustained anticoagulation.

Rate control is noninferior to rhythm control and does not decrease survival, functional capacity, or quality of life. Rate-control medications include beta-blockers, nondihydropyridine CCBs, amiodarone, and digoxin.

When a patient reporting a history of palpitations is symptomatic during assessment, several tachycardias can be detected with the use of vagal maneuvers.

In the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial of 4060 patients, mortality was the same with rhythm control (21.3%) and rate control (23.8%) (HR = 1.15; 95% CI, 0.99-1.34), with no difference in the incidence of cardiac death, arrhythmic death, or death due to stroke.²³ In the RACE (RAte Control versus Electrical cardioversion for persistent atrial fibrillation) trial of 522 patients with persistent AF, rate control was noninferior to rhythm control (by cardioversion and drugs) for reducing morbidity and preventing cardiovascular death.²⁴ One possible reason why the rhythm control strategy in the RACE trial did not show superiority is the low number of patients who achieved sustained sinus rhythm.²⁵

Continue to: The recommended ventricular rate...

The recommended ventricular rate has traditionally been 60 to 80 beats/min at rest and < 110 beats/min during daily activities. However, a recent trial found fewer adverse outcomes and no change in symptoms or the outcome of hospitalization in patients randomized to more lenient control (target resting heart rate, < 110 beats/min), although the mean of the actual lenient rate achieved was 86 beats/minute.²⁴

Rhythm control. Antiarrhythmic agents or procedural interventions can be used in patients who fail or remain symptomatic despite rate control.²⁶ Surgical measures include AV node ablation with placement of a pacemaker; atrial pacing with an implantable atrial defibrillator; the Maze procedure (open-heart surgery) to interrupt reentrant circuits in the left atrium; and percutaneous radiofrequency or cryotherapy ablation of arrhythmogenic foci in and around the junction of the pulmonary veins and left atrium.²⁷

There is no significant benefit to immediate catheter ablation over standard medical therapy in adults with symptomatic AF in reducing the composite outcome of death, stroke, serious bleeding, and cardiac arrest. Catheter ablation is associated with a lower AF recurrence rate (50%) than drug therapy (69%) at 3 years.²⁸

Anticoagulation. Patients at high risk of embolic stroke based on their score on the CHA2DS2-VASc^a risk stratification tool (ie, a score ≥ 2) should be anticoagulated.^29,30 Options include a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban), the preferred class of agents for nonvalvular AF, and warfarin, with a target International Normalized Ratio of 2 to 3. Novel oral anticoagulants have been compared to warfarin for prevention of stroke in AF and were found more effective than warfarin, although at the expense of an increased risk of gastrointestinal bleeding.³¹ Percutaneous left atrial appendage closure, using a device such as the Watchman implant, is a noninferior surgical method to prevent embolic stroke in patients who are intolerant of, or have a contraindication to, anticoagulation.³²

CORRESPONDENCE
Anne Mounsey, MD, Department of Family Medicine, University of North Carolina, 590 Manning Drive, Chapel Hill, NC 27599; Anne_mounsey@med.unc.edu.

Palpitations, the sensory perception of one’s heartbeat, are reported in 16% of primary care patients, from causes that are both cardiac (ie, arrhythmias) and noncardiac.¹ Palpitations are usually benign; overall mortality is approximately 1% annually. In fact, a retrospective study found no difference in mortality and morbidity between patients with palpitations and control patients without palpitations.² However, palpitations can reflect a life-threatening cardiac condition, as we discuss in this article, making careful assessment and targeted, sometimes urgent, intervention important.³

Here, we review the clinical work-up of palpitations, recommended diagnostic testing, and the range of interventions for cardiac arrhythmias—ectopic beats, ventricular tachycardia (VT), and atrial fibrillation (AF).

Cardiac and noncardiac causes of palpitations

In a prospective cohort study of 190 consecutive patients presenting with palpitations, the cause was cardiac in 43%, psychiatric in 31%, and of a miscellaneous nature (including medication, thyrotoxicosis, caffeine, cocaine, anemia, amphetamine, and mastocytosis) in 10%; in 16%, the cause was undetermined.² In this study, 77% of patients experienced a recurrence of palpitations after their first episode.²

Cardiac arrhythmias, a common cause of palpitations, are differentiated by site of origin—supraventricular and ventricular. Noncardiac causes of palpitations, which we do not discuss here, include metabolic and psychiatric conditions, medications, and substance use. (For a summary of the causes of palpitations, see TABLE 1.^2-4)

Common complaint: ectopic beats. Premature atrial contractions (PACs; also known as premature atrial beats, atrial premature complexes, and atrial premature beats) and premature ventricular contractions (PVCs; also known as ventricular premature complexes and ventricular premature beats, and also of a variety of possible causes) result in a feeling of a skipped heartbeat or a flipping sensation in the chest.

Palpitations are usually benign. But they can reflect a life-threatening cardiac condition, making careful assessment and targeted, sometimes urgent, intervention important.

The burden of PACs is independently associated with mortality, cardiovascular hospitalization, new-onset AF, and pacemaker implantation. In a multivariate analysis, a PAC burden > 76 beats/d was an independent predictor of mortality (hazard ratio [HR] = 1.4; 95% CI, 1.2-16); cardiovascular hospitalization (HR = 1.3; 95% CI, 1.1-1.5); new-onset AF (HR = 1.8; 95% CI, 1.4-2.2); and pacemaker implantation (HR = 2.8; 95% CI, 1.9-4.2). Frequent PACs can lead to cardiac remodeling, so more intense follow-up of patients with a high PAC burden might allow for early detection of AF or subclinical cardiac disease.^5,6

A burden of PVCs > 24% is associated with an increased risk of PVC-induced cardiomyopathy and heart failure. Polymorphic PVCs are more concerning than monomorphic PVCs because the former suggests the presence of more diffuse, rather than localized, myocardial injury. The presence of frequent (> 1000 beats/d) PVCs warrants evaluation and treatment for underlying structural heart disease and ischemic heart disease. Therapy directed toward underlying heart disease can reduce the frequency of PVCs.^7-9

Continue to: The diagnostic work-up

The most important goal of the evaluation of palpitations is to determine the presence, or risk, of structural heart or coronary artery disease (CAD) by means of the history, physical examination, and electrocardiography (EKG). Patients who have an increased risk of structural heart disease need further evaluation with echocardiography; those at increased risk of CAD should have stress testing.

Hemodynamically unstable patients need admission; patients who have a history of syncope with palpitations usually should be admitted for cardiac monitoring. Patients who have had a single episode of palpitations and have normal baseline results of laboratory testing and a normal EKG, and no risk factors for structural heart disease or known CAD, can usually be observed.^3,4,10 Patients with an abnormal baseline EKG, recurrent palpitations (especially tachyarrhythmia), or significant symptoms during palpitations (syncope, presyncope, dyspnea) need further evaluation with ambulatory monitoring^3,4,10 (Figure).

Take a thorough history; ask these questions

Have the patient describe the palpitations. The history should include the patient’s detailed characterization of the palpitations (sudden or gradual onset, rhythm, duration, frequency). Certain descriptions provide possible diagnostic clues:

• Palpitations lasting < 5 minutes are less likely to be of cardiac origin (likelihood ratio [LR] = 0.38; 95% CI, 0.2-0.6).⁴
• A patient who has a regular, rapid-pounding sensation in the neck has an increased probability of atrioventricular (AV) nodal reentrant tachycardia (AVNRT) (LR = 177; 95% CI, 25-1251); absence of this sensation decreases the likelihood of AVNRT (LR = 0.07; 95% CI, 0.03-0.2).⁴
• PACs and PVCs cause a sensation of a skipped heartbeat or a flipping sensation in the chest; they are not reported as a sustained rapid heartbeat.
• Patients with a supraventricular arrhythmia often report sudden onset and cessation of palpitations.
• Patients with palpitations since childhood are more likely to have supraventricular tachycardia (SVT).⁴

Elicit apparent precipitating and alleviating factors. The history should include notation of situations that appear to the patient to lead to palpitations (eg, context, positional variation). Palpitations that affect sleep (LR = 2.3; 95% CI, 1.3-3.9) and palpitations that occur at work (LR = 2.2; 95% CI, 1.3-5) increase the likelihood of a cardiac cause.⁴ Palpitations associated with sudden change in position, such as bending forward or squatting, are more likely due to AVNRT.¹¹

Patients with an abnormal baseline EKG, recurrent palpitations, or significant symptoms during palpitations need evaluation with ambulatory monitoring.

Ask about aggravating factors (eg, exercise) and relieving factors (eg, rest, performing a Valsalva maneuver). Patients with SVT are often able to have palpitations terminated with a Valsalva maneuver, such as carotid sinus massage. Palpitations and syncope during exertion can be associated with hypertrophic cardiomyopathy, congenital coronary anomalies, and ion channelopathies, and can cause sudden cardiac death in athletes (estimated incidence, 1-3/100,000 person–years¹²).

Endeavor to identify underlying cardiac disease. A comprehensive history should also evaluate for risk factors and symptoms (chest pain, dyspnea, diaphoresis, lightheadedness, syncope) of cardiac disease, such as CAD, valvular disease, cardiomyopathy, and congenital heart disease, which increase the likelihood that the presenting complaint is a cardiac arrhythmia (LR = 2; 95% CI, 1.3-3.1).⁴ A history of syncope in a patient with palpitations should prompt evaluation for structural heart disease, such as aortic stenosis or hypertrophic cardiomyopathy, in which outflow-tract obstruction impairs cardiac output and, subsequently, cerebral blood flow.

Obtain additional key information. Determine the following in taking the history:

• Is there a family history of inherited cardiac disorders or sudden cardiac death?
• What prescription and over-the-counter medications is the patient taking? How does the patient characterize his or her use/intake of recreational drugs, nicotine, caffeine, and alcohol?
• Does the patient have a history of panic disorder, which lessens concern about a cardiac cause (LR = 0.2; 95% CI, 0.07-1.01)?⁴ (Of note: A nonpsychiatric cause can coexist in such patients, and should be considered.)

Continue to: Physical examination clues, and the utility of vagal maneuvers

Physical examination clues, and the utility of vagal maneuvers

Although most patients in whom palpitations are the presenting complaint are, in fact, asymptomatic during clinical assessment, cardiovascular examination can assist in diagnosing the arrhythmia or structural heart disease:

• Resting bradycardia increases the likelihood of a clinically significant arrhythmia (LR = 3; 95% CI, 1.27-7.0).¹¹
• A murmur, such as a midsystolic click or holosystolic murmur, detected during the cardiac exam can indicate mitral valve prolapse; a holosystolic murmur, exacerbated upon performing a Valsalva maneuver, suggests hypertrophic cardiomyopathy.
• Visible neck pulsations detected during assessment of the jugular venous pressure, known as cannon atrial (cannon A) waves, reflect abnormal contraction of the right atrium against a closed tricuspid valve during AV dissociation. Cannon A waves have an LR of 2.68 (95% CI, 1.25-5.78) for predicting AVNRT.⁴

Vagal nerve stimulation. In the rare circumstance that a patient complaining of palpitations is symptomatic during assessment, several tachycardias can be detected with the use of vagal maneuvers. Interruption of the tachycardia during carotid massage suggests a tachycardia involving the AV junction (AVNRT), whereas only a temporary pause or reduction in frequency is more common in atrial flutter, AF, and atrial tachycardias. Carotid massage has no effect on the presentation of ventricular arrhythmias.¹⁰

Diagnostic testing and the role of ambulatory monitoring

Electrocardiography. All patients with palpitations should have a 12-lead EKG, which may provide diagnostic clues (TABLE 2¹⁰).

Ambulatory monitoring. When the EKG is nondiagnostic, ambulatory cardiac monitoring has an established role in the diagnosis of recurrent palpitations. In a small study of patients presenting with palpitations to a general practitioner, the deduction of those practitioners was wrong more than half the time when they predicted a ≤ 20% chance of an arrhythmia based on the history, physical exam, and EKG alone¹³—emphasizing the importance of ambulatory monitoring in patients with recurrent palpitations.

A comprehensive history should also evaluate for risk factors and symptoms of cardiac disease (chest pain, dyspnea, diaphoresis, lightheadedness, syncope).

Which monitoring system is most suitable depends on symptom frequency, availability, cost, and patient competence. Twenty-four- to 48-hour Holter monitoring can be used in cases of frequent (eg, daily) palpitations. An automatic external loop recorder can be used for less frequent (eg, every 30 days) symptoms. Most ambulatory EKG is now automatic, and therefore does not require patient activation; older manual systems require patient activation during symptoms.

Two weeks of ambulatory EKG have proved sufficient for determining that there is a cardiac basis to palpitations. The diagnostic yield of ambulatory EKG is highest during Week 1 (1.04 diagnoses per patient), compared to Week 3 (0.17 diagnoses per patient).¹⁴

Implantable loop recorders are placed subcutaneously to provide EKG monitoring for approximately 3 years. They are better suited for diagnosing infrequent palpitations. The diagnostic yield of an implantable loop recorder over the course of 1 year for the detection of an arrhythmia is 73%, compared to 21% for a 24-hour Holter monitor, electrophysiology studies, and 4 weeks of an external loop recorder.¹⁵ Implantable loop recorders are often reserved for patients with palpitations associated with unexplained recurrent syncope.¹⁵

Continue to: Lab work

Lab work. A comprehensive metabolic panel, complete blood count, lipid panel, and thyroid panel should be ordered for all patients with palpitations. Possible additional tests include a urine drug screen (when recreational drug use is suspected); cardiac enzymes; N-terminal-pro hormone B-type natriuretic peptide (when there is evidence of CAD or heart failure); and urinary catecholamines (when pheochromocytoma is suspected).

Other investigations. Echocardiography is indicated when structural heart disease is suspected (TABLE 1^2-4). Patients who have multiple risk factors for CAD or exertional symptoms might warrant a stress test.

Management

PACs and PVCs

Typically, patients are counseled to minimize potential adrenergic precipitants, such as smoking, alcohol, stress, and caffeine. However, limited studies have demonstrated no significant arrhythmogenic potential of a modest dose of caffeine (200 mg), even in patients with known life-threatening ventricular arrhythmias.¹⁶ Beta-blockers and nondihydropyridine calcium channel blockers (CCBs) can reduce the severity of symptoms related to premature ectopic beats and might reduce their frequency, although response is inconsistent. Use of these medications for PACs is largely based on expert opinion and extrapolated from use in other supraventricular and ventricular arrhythmias.

Implantable cardioverter defibrillator therapy is indicated in patients with nonsustained VT due to prior myocardial infarction, left ventricular ejection fraction ≤ 40%, and inducible ventricular fibrillation or sustained VT on electrophysiological study.⁷

Patients with a high burden of ectopy who do not respond to treatment with AV nodal-blocking agents should be referred to Cardiology for other antiarrhythmic agents or catheter ablation. Last, asymptomatic ectopy does not need to be treated; there is no clear evidence that suppression with pharmacotherapy improves overall survival.^15,17

Supraventricular tachycardia

The priority when evaluating any tachycardia is to assess the patient’s stability. Unstable patients should be treated immediately, usually with cardioversion, before an extensive diagnostic evaluation.¹⁸ Patients with wide-complex tachycardia (QRS > 120 ms) are generally more unstable and require more urgent therapy and cardiac consultation or referral. Hemodynamically stable patients with narrow-complex SVT (QRS < 120 ms) can be treated with IV adenosine, which has an 89.7% success rate.^18,19 If adenosine is unsuccessful, cardioversion is indicated.

Stable patients with minimal symptoms and short episodes do not need treatment.

Continue to: Vagal maneuvers

Vagal maneuvers (eg, Valsalva maneuver; unilateral carotid massage after exclusion of a carotid bruit, with head tilted to the side opposite the massage, and not for longer than 10 seconds; or applying an ice-cold wet towel to the face) have a success rate of about 25% and are most effective when performed shortly after onset of arrhythmia. Vagal maneuvers can be used in all patients while preparing to administer medications.²⁰

Patients who need treatment can take the “pill-in-the-pocket” approach with single-dose oral flecainide (3 mg/kg) or combined diltiazem and propranolol. Flecainide has a 94% success rate; diltiazem–propranolol has a lower success rate (61%) but a shorter time to conversion to sinus rhythm.²¹ Patients with sustained or recurrent episodes of SVT should be referred to a cardiologist for chronic prophylactic drug therapy or radiofrequency ablation.

Atrial fibrillation

Hemodynamically unstable patients with AF or atrial flutter, defined by the presence of angina, decompensated heart failure, hypotension, pulmonary edema, or evidence of organ hypoperfusion, should be electrically cardioverted using synchronized direct current.

Hemodynamically stable patients with a rapid ventricular rate should be treated with an IV or oral beta-blocker, CCB, or amiodarone, or electrically cardioverted. IV medications are typically preferred in the acute setting for ease and rapidity of administration; however, there is no evidence that IV formulations of beta-blockers and CCBs are superior to oral formulations. Once the ventricular rate is controlled, patients can be transitioned to an oral short-acting preparation of the selected agent, then converted to an appropriate dosage of an extended-­release preparation.²²

Cardioversion can be performed in patients with AF < 48 hours. In patients with AF > 48 hours, either 4 weeks of anticoagulation can be given, followed by cardioversion, or transesophageal echocardiography should be performed to evaluate for atrial thrombus; if atrial thrombus is absent, cardioversion can be performed.²² Transesophageal echocardiography might be unnecessary in patients known to have been on sustained anticoagulation.

Rate control is noninferior to rhythm control and does not decrease survival, functional capacity, or quality of life. Rate-control medications include beta-blockers, nondihydropyridine CCBs, amiodarone, and digoxin.

When a patient reporting a history of palpitations is symptomatic during assessment, several tachycardias can be detected with the use of vagal maneuvers.

In the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial of 4060 patients, mortality was the same with rhythm control (21.3%) and rate control (23.8%) (HR = 1.15; 95% CI, 0.99-1.34), with no difference in the incidence of cardiac death, arrhythmic death, or death due to stroke.²³ In the RACE (RAte Control versus Electrical cardioversion for persistent atrial fibrillation) trial of 522 patients with persistent AF, rate control was noninferior to rhythm control (by cardioversion and drugs) for reducing morbidity and preventing cardiovascular death.²⁴ One possible reason why the rhythm control strategy in the RACE trial did not show superiority is the low number of patients who achieved sustained sinus rhythm.²⁵

Continue to: The recommended ventricular rate...

The recommended ventricular rate has traditionally been 60 to 80 beats/min at rest and < 110 beats/min during daily activities. However, a recent trial found fewer adverse outcomes and no change in symptoms or the outcome of hospitalization in patients randomized to more lenient control (target resting heart rate, < 110 beats/min), although the mean of the actual lenient rate achieved was 86 beats/minute.²⁴

Rhythm control. Antiarrhythmic agents or procedural interventions can be used in patients who fail or remain symptomatic despite rate control.²⁶ Surgical measures include AV node ablation with placement of a pacemaker; atrial pacing with an implantable atrial defibrillator; the Maze procedure (open-heart surgery) to interrupt reentrant circuits in the left atrium; and percutaneous radiofrequency or cryotherapy ablation of arrhythmogenic foci in and around the junction of the pulmonary veins and left atrium.²⁷

There is no significant benefit to immediate catheter ablation over standard medical therapy in adults with symptomatic AF in reducing the composite outcome of death, stroke, serious bleeding, and cardiac arrest. Catheter ablation is associated with a lower AF recurrence rate (50%) than drug therapy (69%) at 3 years.²⁸

Anticoagulation. Patients at high risk of embolic stroke based on their score on the CHA2DS2-VASc^a risk stratification tool (ie, a score ≥ 2) should be anticoagulated.^29,30 Options include a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban), the preferred class of agents for nonvalvular AF, and warfarin, with a target International Normalized Ratio of 2 to 3. Novel oral anticoagulants have been compared to warfarin for prevention of stroke in AF and were found more effective than warfarin, although at the expense of an increased risk of gastrointestinal bleeding.³¹ Percutaneous left atrial appendage closure, using a device such as the Watchman implant, is a noninferior surgical method to prevent embolic stroke in patients who are intolerant of, or have a contraindication to, anticoagulation.³²

CORRESPONDENCE
Anne Mounsey, MD, Department of Family Medicine, University of North Carolina, 590 Manning Drive, Chapel Hill, NC 27599; Anne_mounsey@med.unc.edu.

Palpitations, the sensory perception of one’s heartbeat, are reported in 16% of primary care patients, from causes that are both cardiac (ie, arrhythmias) and noncardiac.¹ Palpitations are usually benign; overall mortality is approximately 1% annually. In fact, a retrospective study found no difference in mortality and morbidity between patients with palpitations and control patients without palpitations.² However, palpitations can reflect a life-threatening cardiac condition, as we discuss in this article, making careful assessment and targeted, sometimes urgent, intervention important.³

Here, we review the clinical work-up of palpitations, recommended diagnostic testing, and the range of interventions for cardiac arrhythmias—ectopic beats, ventricular tachycardia (VT), and atrial fibrillation (AF).

Cardiac and noncardiac causes of palpitations

In a prospective cohort study of 190 consecutive patients presenting with palpitations, the cause was cardiac in 43%, psychiatric in 31%, and of a miscellaneous nature (including medication, thyrotoxicosis, caffeine, cocaine, anemia, amphetamine, and mastocytosis) in 10%; in 16%, the cause was undetermined.² In this study, 77% of patients experienced a recurrence of palpitations after their first episode.²

Cardiac arrhythmias, a common cause of palpitations, are differentiated by site of origin—supraventricular and ventricular. Noncardiac causes of palpitations, which we do not discuss here, include metabolic and psychiatric conditions, medications, and substance use. (For a summary of the causes of palpitations, see TABLE 1.^2-4)

Common complaint: ectopic beats. Premature atrial contractions (PACs; also known as premature atrial beats, atrial premature complexes, and atrial premature beats) and premature ventricular contractions (PVCs; also known as ventricular premature complexes and ventricular premature beats, and also of a variety of possible causes) result in a feeling of a skipped heartbeat or a flipping sensation in the chest.

Palpitations are usually benign. But they can reflect a life-threatening cardiac condition, making careful assessment and targeted, sometimes urgent, intervention important.

The burden of PACs is independently associated with mortality, cardiovascular hospitalization, new-onset AF, and pacemaker implantation. In a multivariate analysis, a PAC burden > 76 beats/d was an independent predictor of mortality (hazard ratio [HR] = 1.4; 95% CI, 1.2-16); cardiovascular hospitalization (HR = 1.3; 95% CI, 1.1-1.5); new-onset AF (HR = 1.8; 95% CI, 1.4-2.2); and pacemaker implantation (HR = 2.8; 95% CI, 1.9-4.2). Frequent PACs can lead to cardiac remodeling, so more intense follow-up of patients with a high PAC burden might allow for early detection of AF or subclinical cardiac disease.^5,6

A burden of PVCs > 24% is associated with an increased risk of PVC-induced cardiomyopathy and heart failure. Polymorphic PVCs are more concerning than monomorphic PVCs because the former suggests the presence of more diffuse, rather than localized, myocardial injury. The presence of frequent (> 1000 beats/d) PVCs warrants evaluation and treatment for underlying structural heart disease and ischemic heart disease. Therapy directed toward underlying heart disease can reduce the frequency of PVCs.^7-9

Continue to: The diagnostic work-up

The most important goal of the evaluation of palpitations is to determine the presence, or risk, of structural heart or coronary artery disease (CAD) by means of the history, physical examination, and electrocardiography (EKG). Patients who have an increased risk of structural heart disease need further evaluation with echocardiography; those at increased risk of CAD should have stress testing.

Hemodynamically unstable patients need admission; patients who have a history of syncope with palpitations usually should be admitted for cardiac monitoring. Patients who have had a single episode of palpitations and have normal baseline results of laboratory testing and a normal EKG, and no risk factors for structural heart disease or known CAD, can usually be observed.^3,4,10 Patients with an abnormal baseline EKG, recurrent palpitations (especially tachyarrhythmia), or significant symptoms during palpitations (syncope, presyncope, dyspnea) need further evaluation with ambulatory monitoring^3,4,10 (Figure).

Take a thorough history; ask these questions

Have the patient describe the palpitations. The history should include the patient’s detailed characterization of the palpitations (sudden or gradual onset, rhythm, duration, frequency). Certain descriptions provide possible diagnostic clues:

• Palpitations lasting < 5 minutes are less likely to be of cardiac origin (likelihood ratio [LR] = 0.38; 95% CI, 0.2-0.6).⁴
• A patient who has a regular, rapid-pounding sensation in the neck has an increased probability of atrioventricular (AV) nodal reentrant tachycardia (AVNRT) (LR = 177; 95% CI, 25-1251); absence of this sensation decreases the likelihood of AVNRT (LR = 0.07; 95% CI, 0.03-0.2).⁴
• PACs and PVCs cause a sensation of a skipped heartbeat or a flipping sensation in the chest; they are not reported as a sustained rapid heartbeat.
• Patients with a supraventricular arrhythmia often report sudden onset and cessation of palpitations.
• Patients with palpitations since childhood are more likely to have supraventricular tachycardia (SVT).⁴

Elicit apparent precipitating and alleviating factors. The history should include notation of situations that appear to the patient to lead to palpitations (eg, context, positional variation). Palpitations that affect sleep (LR = 2.3; 95% CI, 1.3-3.9) and palpitations that occur at work (LR = 2.2; 95% CI, 1.3-5) increase the likelihood of a cardiac cause.⁴ Palpitations associated with sudden change in position, such as bending forward or squatting, are more likely due to AVNRT.¹¹

Patients with an abnormal baseline EKG, recurrent palpitations, or significant symptoms during palpitations need evaluation with ambulatory monitoring.

Ask about aggravating factors (eg, exercise) and relieving factors (eg, rest, performing a Valsalva maneuver). Patients with SVT are often able to have palpitations terminated with a Valsalva maneuver, such as carotid sinus massage. Palpitations and syncope during exertion can be associated with hypertrophic cardiomyopathy, congenital coronary anomalies, and ion channelopathies, and can cause sudden cardiac death in athletes (estimated incidence, 1-3/100,000 person–years¹²).

Endeavor to identify underlying cardiac disease. A comprehensive history should also evaluate for risk factors and symptoms (chest pain, dyspnea, diaphoresis, lightheadedness, syncope) of cardiac disease, such as CAD, valvular disease, cardiomyopathy, and congenital heart disease, which increase the likelihood that the presenting complaint is a cardiac arrhythmia (LR = 2; 95% CI, 1.3-3.1).⁴ A history of syncope in a patient with palpitations should prompt evaluation for structural heart disease, such as aortic stenosis or hypertrophic cardiomyopathy, in which outflow-tract obstruction impairs cardiac output and, subsequently, cerebral blood flow.

Obtain additional key information. Determine the following in taking the history:

• Is there a family history of inherited cardiac disorders or sudden cardiac death?
• What prescription and over-the-counter medications is the patient taking? How does the patient characterize his or her use/intake of recreational drugs, nicotine, caffeine, and alcohol?
• Does the patient have a history of panic disorder, which lessens concern about a cardiac cause (LR = 0.2; 95% CI, 0.07-1.01)?⁴ (Of note: A nonpsychiatric cause can coexist in such patients, and should be considered.)

Continue to: Physical examination clues, and the utility of vagal maneuvers

Physical examination clues, and the utility of vagal maneuvers

Although most patients in whom palpitations are the presenting complaint are, in fact, asymptomatic during clinical assessment, cardiovascular examination can assist in diagnosing the arrhythmia or structural heart disease:

• Resting bradycardia increases the likelihood of a clinically significant arrhythmia (LR = 3; 95% CI, 1.27-7.0).¹¹
• A murmur, such as a midsystolic click or holosystolic murmur, detected during the cardiac exam can indicate mitral valve prolapse; a holosystolic murmur, exacerbated upon performing a Valsalva maneuver, suggests hypertrophic cardiomyopathy.
• Visible neck pulsations detected during assessment of the jugular venous pressure, known as cannon atrial (cannon A) waves, reflect abnormal contraction of the right atrium against a closed tricuspid valve during AV dissociation. Cannon A waves have an LR of 2.68 (95% CI, 1.25-5.78) for predicting AVNRT.⁴

Vagal nerve stimulation. In the rare circumstance that a patient complaining of palpitations is symptomatic during assessment, several tachycardias can be detected with the use of vagal maneuvers. Interruption of the tachycardia during carotid massage suggests a tachycardia involving the AV junction (AVNRT), whereas only a temporary pause or reduction in frequency is more common in atrial flutter, AF, and atrial tachycardias. Carotid massage has no effect on the presentation of ventricular arrhythmias.¹⁰

Diagnostic testing and the role of ambulatory monitoring

Electrocardiography. All patients with palpitations should have a 12-lead EKG, which may provide diagnostic clues (TABLE 2¹⁰).

Ambulatory monitoring. When the EKG is nondiagnostic, ambulatory cardiac monitoring has an established role in the diagnosis of recurrent palpitations. In a small study of patients presenting with palpitations to a general practitioner, the deduction of those practitioners was wrong more than half the time when they predicted a ≤ 20% chance of an arrhythmia based on the history, physical exam, and EKG alone¹³—emphasizing the importance of ambulatory monitoring in patients with recurrent palpitations.

A comprehensive history should also evaluate for risk factors and symptoms of cardiac disease (chest pain, dyspnea, diaphoresis, lightheadedness, syncope).

Which monitoring system is most suitable depends on symptom frequency, availability, cost, and patient competence. Twenty-four- to 48-hour Holter monitoring can be used in cases of frequent (eg, daily) palpitations. An automatic external loop recorder can be used for less frequent (eg, every 30 days) symptoms. Most ambulatory EKG is now automatic, and therefore does not require patient activation; older manual systems require patient activation during symptoms.

Two weeks of ambulatory EKG have proved sufficient for determining that there is a cardiac basis to palpitations. The diagnostic yield of ambulatory EKG is highest during Week 1 (1.04 diagnoses per patient), compared to Week 3 (0.17 diagnoses per patient).¹⁴

Implantable loop recorders are placed subcutaneously to provide EKG monitoring for approximately 3 years. They are better suited for diagnosing infrequent palpitations. The diagnostic yield of an implantable loop recorder over the course of 1 year for the detection of an arrhythmia is 73%, compared to 21% for a 24-hour Holter monitor, electrophysiology studies, and 4 weeks of an external loop recorder.¹⁵ Implantable loop recorders are often reserved for patients with palpitations associated with unexplained recurrent syncope.¹⁵

Continue to: Lab work

Lab work. A comprehensive metabolic panel, complete blood count, lipid panel, and thyroid panel should be ordered for all patients with palpitations. Possible additional tests include a urine drug screen (when recreational drug use is suspected); cardiac enzymes; N-terminal-pro hormone B-type natriuretic peptide (when there is evidence of CAD or heart failure); and urinary catecholamines (when pheochromocytoma is suspected).

Other investigations. Echocardiography is indicated when structural heart disease is suspected (TABLE 1^2-4). Patients who have multiple risk factors for CAD or exertional symptoms might warrant a stress test.

Management

PACs and PVCs

Typically, patients are counseled to minimize potential adrenergic precipitants, such as smoking, alcohol, stress, and caffeine. However, limited studies have demonstrated no significant arrhythmogenic potential of a modest dose of caffeine (200 mg), even in patients with known life-threatening ventricular arrhythmias.¹⁶ Beta-blockers and nondihydropyridine calcium channel blockers (CCBs) can reduce the severity of symptoms related to premature ectopic beats and might reduce their frequency, although response is inconsistent. Use of these medications for PACs is largely based on expert opinion and extrapolated from use in other supraventricular and ventricular arrhythmias.

Implantable cardioverter defibrillator therapy is indicated in patients with nonsustained VT due to prior myocardial infarction, left ventricular ejection fraction ≤ 40%, and inducible ventricular fibrillation or sustained VT on electrophysiological study.⁷

Patients with a high burden of ectopy who do not respond to treatment with AV nodal-blocking agents should be referred to Cardiology for other antiarrhythmic agents or catheter ablation. Last, asymptomatic ectopy does not need to be treated; there is no clear evidence that suppression with pharmacotherapy improves overall survival.^15,17

Supraventricular tachycardia

The priority when evaluating any tachycardia is to assess the patient’s stability. Unstable patients should be treated immediately, usually with cardioversion, before an extensive diagnostic evaluation.¹⁸ Patients with wide-complex tachycardia (QRS > 120 ms) are generally more unstable and require more urgent therapy and cardiac consultation or referral. Hemodynamically stable patients with narrow-complex SVT (QRS < 120 ms) can be treated with IV adenosine, which has an 89.7% success rate.^18,19 If adenosine is unsuccessful, cardioversion is indicated.

Stable patients with minimal symptoms and short episodes do not need treatment.

Continue to: Vagal maneuvers

Vagal maneuvers (eg, Valsalva maneuver; unilateral carotid massage after exclusion of a carotid bruit, with head tilted to the side opposite the massage, and not for longer than 10 seconds; or applying an ice-cold wet towel to the face) have a success rate of about 25% and are most effective when performed shortly after onset of arrhythmia. Vagal maneuvers can be used in all patients while preparing to administer medications.²⁰

Patients who need treatment can take the “pill-in-the-pocket” approach with single-dose oral flecainide (3 mg/kg) or combined diltiazem and propranolol. Flecainide has a 94% success rate; diltiazem–propranolol has a lower success rate (61%) but a shorter time to conversion to sinus rhythm.²¹ Patients with sustained or recurrent episodes of SVT should be referred to a cardiologist for chronic prophylactic drug therapy or radiofrequency ablation.

Atrial fibrillation

Hemodynamically unstable patients with AF or atrial flutter, defined by the presence of angina, decompensated heart failure, hypotension, pulmonary edema, or evidence of organ hypoperfusion, should be electrically cardioverted using synchronized direct current.

Hemodynamically stable patients with a rapid ventricular rate should be treated with an IV or oral beta-blocker, CCB, or amiodarone, or electrically cardioverted. IV medications are typically preferred in the acute setting for ease and rapidity of administration; however, there is no evidence that IV formulations of beta-blockers and CCBs are superior to oral formulations. Once the ventricular rate is controlled, patients can be transitioned to an oral short-acting preparation of the selected agent, then converted to an appropriate dosage of an extended-­release preparation.²²

Cardioversion can be performed in patients with AF < 48 hours. In patients with AF > 48 hours, either 4 weeks of anticoagulation can be given, followed by cardioversion, or transesophageal echocardiography should be performed to evaluate for atrial thrombus; if atrial thrombus is absent, cardioversion can be performed.²² Transesophageal echocardiography might be unnecessary in patients known to have been on sustained anticoagulation.

Rate control is noninferior to rhythm control and does not decrease survival, functional capacity, or quality of life. Rate-control medications include beta-blockers, nondihydropyridine CCBs, amiodarone, and digoxin.

When a patient reporting a history of palpitations is symptomatic during assessment, several tachycardias can be detected with the use of vagal maneuvers.

In the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial of 4060 patients, mortality was the same with rhythm control (21.3%) and rate control (23.8%) (HR = 1.15; 95% CI, 0.99-1.34), with no difference in the incidence of cardiac death, arrhythmic death, or death due to stroke.²³ In the RACE (RAte Control versus Electrical cardioversion for persistent atrial fibrillation) trial of 522 patients with persistent AF, rate control was noninferior to rhythm control (by cardioversion and drugs) for reducing morbidity and preventing cardiovascular death.²⁴ One possible reason why the rhythm control strategy in the RACE trial did not show superiority is the low number of patients who achieved sustained sinus rhythm.²⁵

Continue to: The recommended ventricular rate...

The recommended ventricular rate has traditionally been 60 to 80 beats/min at rest and < 110 beats/min during daily activities. However, a recent trial found fewer adverse outcomes and no change in symptoms or the outcome of hospitalization in patients randomized to more lenient control (target resting heart rate, < 110 beats/min), although the mean of the actual lenient rate achieved was 86 beats/minute.²⁴

Rhythm control. Antiarrhythmic agents or procedural interventions can be used in patients who fail or remain symptomatic despite rate control.²⁶ Surgical measures include AV node ablation with placement of a pacemaker; atrial pacing with an implantable atrial defibrillator; the Maze procedure (open-heart surgery) to interrupt reentrant circuits in the left atrium; and percutaneous radiofrequency or cryotherapy ablation of arrhythmogenic foci in and around the junction of the pulmonary veins and left atrium.²⁷

There is no significant benefit to immediate catheter ablation over standard medical therapy in adults with symptomatic AF in reducing the composite outcome of death, stroke, serious bleeding, and cardiac arrest. Catheter ablation is associated with a lower AF recurrence rate (50%) than drug therapy (69%) at 3 years.²⁸

Anticoagulation. Patients at high risk of embolic stroke based on their score on the CHA2DS2-VASc^a risk stratification tool (ie, a score ≥ 2) should be anticoagulated.^29,30 Options include a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban), the preferred class of agents for nonvalvular AF, and warfarin, with a target International Normalized Ratio of 2 to 3. Novel oral anticoagulants have been compared to warfarin for prevention of stroke in AF and were found more effective than warfarin, although at the expense of an increased risk of gastrointestinal bleeding.³¹ Percutaneous left atrial appendage closure, using a device such as the Watchman implant, is a noninferior surgical method to prevent embolic stroke in patients who are intolerant of, or have a contraindication to, anticoagulation.³²

CORRESPONDENCE
Anne Mounsey, MD, Department of Family Medicine, University of North Carolina, 590 Manning Drive, Chapel Hill, NC 27599; Anne_mounsey@med.unc.edu.