MDedge Cardiology

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

Increased psychosocial resilience, which captures a sense of purpose, optimism, and life-coping strategies, correlates with improved cardiovascular (CV) health in Black Americans, according to a study that might hold a key for identifying new strategies for CV disease prevention.

Courtesy Yale University

“Our findings highlight the importance of individual psychosocial factors that promote cardiovascular health among Black adults, traditionally considered to be a high-risk population,” according to a team of authors collaborating on a study produced by the Morehouse-Emory Cardiovascular Center for Health Equity in Atlanta.

Studies associating psychosocial resilience with improved health outcomes have been published before. In a 12-study review of this concept, it was emphasized that resilience is a dynamic process, not a personality trait, and has shown promise as a target of efforts to relieve the burden of disease (Johnston MC et al. Psychosomatics 2015;56:168-80).

In this study, which received partial support from the American Heart Association, psychosocial resilience was evaluated at both the individual level and at the community level among 389 Black adults living in Atlanta. The senior author was Tené T. Lewis, PhD, of the department of epidemiology at Emory’s Rollins School of Public Health (Circ Cardiovasc Qual Outcomes 2020 Oct 7;13:3006638).

Psychosocial resilience was calculated across the domains of environmental mastery, purpose of life, optimism, coping, and lack of depression with standardized tests, such as the Life Orientation Test-Revised questionnaire for optimism and the Ryff Scales of Psychological Well-Being for the domains of environmental mastery and purpose of life. A composite score for psychosocial resilience was reached by calculating the median score across the measured domains.

Patients with high psychosocial resilience, defined as a composite score above the median, or low resilience, defined as a lower score, were then compared for CV health based on the AHA’s Life’s Simple 7 (LS7) score.

LS7 scores incorporate measures for exercise, diet, smoking history, blood pressure, glucose, cholesterol, and body mass index. Composite LS7 scores range from 0 to 14. Prior work cited by the authors have associated each 1-unit increase in LS7 score with a 13% lower risk of CVD.

As a continuous variable for CV risk at the individual level, each higher standard-deviation increment in the composite psychosocial resilience score was associated with a highly significant 0.42-point increase in LS7 score (P < .001) for study participants. In other words, increasing resilience predicted lower CV risk scores.

Resilience was also calculated at the community level by looking at census tract-level rates of CV mortality and morbidity relative to socioeconomic status. Again, high CV resilience, defined as scores above the median, were compared with lower scores across neighborhoods with similar median household income. As a continuous variable in this analysis, each higher standard-deviation increment in the resilience score was associated with a 0.27-point increase in LS7 score (P = .01).

After adjustment for sociodemographic factors, the association between psychosocial resilience and CV health remained significant for both the individual and community calculations, according to the authors. When examined jointly, high individual psychosocial resilience remained independently associated with improved CV health, but living in a high-resilience neighborhood was not an independent predictor.

When evaluated individually, each of the domains in the psychosocial resistance score were positively correlated with higher LS7 scores, meaning lower CV risk. The strongest associations on a statistical level were low depressive symptoms (P = .001), environmental mastery (P = .006), and purpose in life (P = .009).

The impact of high psychosocial resistance scores was greatest in Black adults living in low-resilience neighborhoods. Among these subjects, high resilience was associated with a nearly 1-point increase in LS7 score relative to low resilience (8.38 vs. 7.42). This was unexpected, but it “is consistent with some broader conceptual literature that posits that individual psychosocial resilience matters more under conditions of adversity,” the authors reported.
 

Understanding disparities is key

Black race has repeatedly been associated with an increased risk of CV events, but this study is valuable for providing a fresh perspective on the potential reasons, according to the authors of an accompanying editorial, Amber E. Johnson, MD, and Jared Magnani, MD, who are both affiliated with the division of cardiology at the University of Pittsburgh (Circ Cardiovasc Qual Outcomes 2020 Oct 7. doi: 10.1161/CIRCOUTCOMES.120.007357.

“Clinicians increasingly recognize that race-based disparities do not stem inherently from race; instead, the disparities stem from the underlying social determinations of health,” they wrote, citing such variables as unequal access to pay and acceptable living conditions “and the structural racism that perpetuates them.”

They agreed with the authors that promotion of psychosocial resilience among Black people living in communities with poor CV health has the potential to improve CV outcomes, but they warned that this is complex. Although they contend that resilience techniques can be taught, they cautioned there might be limitations if the underlying factors associated with poor psychosocial resilience remain unchanged.

“Thus, the superficial application of positive psychology strategies is likely insufficient to bring parity to CV health outcomes,” they wrote, concluding that strategies to promote health equity would negate the need for interventions to bolster resilience.

Studies that focus on Black adults and cardiovascular health, including this investigation into the role of psychosocial factors “are much needed and very welcome,” said Harlan M. Krumholz, MD, a cardiologist and professor in the Institute for Social and Policy Studies at Yale University, New Haven, Conn.

He sees a broad array of potential directions of research.

“The study opens many questions about whether the resilience can be strengthened by interventions; whether addressing structural racism could reduce the need for such resilience, and whether this association is specific to Black adults in an urban center or is generally present in other settings and in other populations,” Dr. Krumholz said.

An effort is now needed to determine “whether this is a marker or a mediator of cardiovascular health,” he added.

In either case, resilience is a potentially important factor for understanding racial disparities in CV-disease prevalence and outcomes, according to the authors of the accompanying editorial and Dr. Krumholz.

SOURCE: Kim JH et al. Circ Cardiovasc Qual Outcomes. 2020 Oct 7;13:e006638.

Radiotherapy planning scans may be a rich untapped source of information for estimating the risk of cardiovascular disease (CVD) in breast cancer patients, a large study suggests.

Photo courtesy of Ivar Pel

Researchers found that breast cancer patients with a coronary artery calcifications (CAC) score exceeding 400 had nearly four times the adjusted risk of fatal and nonfatal CVD events when compared with patients who had a CAC score of 0.

Patients with scores exceeding 400 also had more than eight times the risk of coronary heart disease events. The associations were especially strong in the subset of patients who received anthracycline-containing chemotherapy.

Helena Verkooijen, MD, PhD, of University Medical Center Utrecht (the Netherlands) presented these findings at the 12th European Breast Cancer Conference.

Dr. Verkooijen noted that, over the past 50 years, breast cancer has dramatically declined as a cause of death among breast cancer survivors, while CVD has continued to account for about 20% of the total deaths in this population.

CACs are sometimes incidentally seen in radiotherapy planning CT scans. “Right now, this information is not often used for patient stratification or informing patients about their cardiovascular risk, and this is a pity, because we know that it is an independent risk factor, and, often, the presence of calcifications can occur in the absence of other cardiovascular risk factors,” Dr. Verkooijen said.
 

Study details

Dr. Verkooijen and and colleagues from the Bragataston Study Group retrospectively studied 15,919 breast cancer patients who had radiotherapy planning CT scans during 2004-2016 at three Dutch institutions.

The researchers used an automated deep-learning algorithm (described in Radiology) to detect and quantify coronary calcium in planning CT scans and calculate CAC scores, classifying them into five categories.

The median follow-up was 51.6 months. Most women (70%) did not have any calcium detected in their coronary arteries (CAC score of 0), while 3% fell into the highest category (CAC score of >400).

The incidence of nonfatal and fatal CVD events increased with CAC score:

• 5.1% with a score of 0.
• 8.5% with a score of 1-10.
• 13.5% with a score of 11-100.
• 17.6% with a score of 101-400.
• 28.0% with a score greater than 400.

In analyses adjusted for age, laterality of radiation, and receipt of cardiotoxic agents – anthracyclines and trastuzumab – women with a score exceeding 400 had sharply elevated adjusted risks of CVD events (hazard ratio, 3.7), of coronary heart disease events specifically (HR, 8.2), and of death from any cause (HR, 2.8), when compared with peers who had a CAC score of 0.

On further scrutiny of CVD events, the pattern was similar regardless of whether radiation was left- or right-sided. However, the association was stronger among women who received anthracyclines as compared with counterparts who did not, with a nearly six-fold higher risk for those with highest versus lowest CAC scores.

When the women were surveyed, nearly 90% said they wanted to be informed about their CAC score and associated CVD risk, even in the absence of evidence-based risk reduction strategies.
 

Applying the results

“We believe that this is the first time that anyone has conducted a study on this topic on a scale like this, and we show that it is possible to relatively easily identify women at a very high risk of CVD,” Dr. Verkooijen said. “But what do we do with this information, because these scans are not made to answer this question. … This is information that we get that we haven’t really requested. I think we should only use this information when we have really shown that we can help patients reduce their risk of cardiovascular disease.”

To that end, Dr. Verkooijen and colleagues are planning additional research that will look at the potential benefit of referring high-risk patients for cardioprevention strategies and at the role of using the CAC score to personalize treatment strategies.

“This is an interesting and novel approach to predicting cardiac events for patients undergoing breast cancer treatment,” Meena S. Moran, MD, of Yale University in New Haven, Conn., commented in an interview.

The approach would likely be feasible in typical practice with widespread availability of the automated algorithm and might even alter treatment planning in real time, she said. “From the standpoint of radiation oncology, it would mean running the software to generate a CAC score, which would allow for modifications in decision-making during treatment planning, such as whether or not to include the internal mammary nodal chain in a patient who may be in the ‘gray zone’ for regional nodal radiation. For example, if a patient has a high CAC score, plus if they have received (or are receiving) cardiotoxic drugs, radiation oncologists can use that information as an additional factor to consider in the decision-making of whether or not to include the internal mammary chain, which inevitably can increase the dose delivered to the heart,” Dr. Moran elaborated.

Dr. Verkooijen’s study was supported by the Dutch Cancer Society, the European Commission, the Dutch Digestive Foundation, the Netherlands Organisation for Scientific Research, and Elekta. Dr. Verkooijen and Dr. Moran disclosed no conflicts of interest.

SOURCE: Gal R et al. EBCC-12 Virtual Congress, Abstract 7.

Radiotherapy planning scans may be a rich untapped source of information for estimating the risk of cardiovascular disease (CVD) in breast cancer patients, a large study suggests.

Photo courtesy of Ivar Pel

Researchers found that breast cancer patients with a coronary artery calcifications (CAC) score exceeding 400 had nearly four times the adjusted risk of fatal and nonfatal CVD events when compared with patients who had a CAC score of 0.

Patients with scores exceeding 400 also had more than eight times the risk of coronary heart disease events. The associations were especially strong in the subset of patients who received anthracycline-containing chemotherapy.

Helena Verkooijen, MD, PhD, of University Medical Center Utrecht (the Netherlands) presented these findings at the 12th European Breast Cancer Conference.

Dr. Verkooijen noted that, over the past 50 years, breast cancer has dramatically declined as a cause of death among breast cancer survivors, while CVD has continued to account for about 20% of the total deaths in this population.

CACs are sometimes incidentally seen in radiotherapy planning CT scans. “Right now, this information is not often used for patient stratification or informing patients about their cardiovascular risk, and this is a pity, because we know that it is an independent risk factor, and, often, the presence of calcifications can occur in the absence of other cardiovascular risk factors,” Dr. Verkooijen said.
 

Study details

Dr. Verkooijen and and colleagues from the Bragataston Study Group retrospectively studied 15,919 breast cancer patients who had radiotherapy planning CT scans during 2004-2016 at three Dutch institutions.

The researchers used an automated deep-learning algorithm (described in Radiology) to detect and quantify coronary calcium in planning CT scans and calculate CAC scores, classifying them into five categories.

The median follow-up was 51.6 months. Most women (70%) did not have any calcium detected in their coronary arteries (CAC score of 0), while 3% fell into the highest category (CAC score of >400).

The incidence of nonfatal and fatal CVD events increased with CAC score:

• 5.1% with a score of 0.
• 8.5% with a score of 1-10.
• 13.5% with a score of 11-100.
• 17.6% with a score of 101-400.
• 28.0% with a score greater than 400.

In analyses adjusted for age, laterality of radiation, and receipt of cardiotoxic agents – anthracyclines and trastuzumab – women with a score exceeding 400 had sharply elevated adjusted risks of CVD events (hazard ratio, 3.7), of coronary heart disease events specifically (HR, 8.2), and of death from any cause (HR, 2.8), when compared with peers who had a CAC score of 0.

On further scrutiny of CVD events, the pattern was similar regardless of whether radiation was left- or right-sided. However, the association was stronger among women who received anthracyclines as compared with counterparts who did not, with a nearly six-fold higher risk for those with highest versus lowest CAC scores.

When the women were surveyed, nearly 90% said they wanted to be informed about their CAC score and associated CVD risk, even in the absence of evidence-based risk reduction strategies.
 

Applying the results

“We believe that this is the first time that anyone has conducted a study on this topic on a scale like this, and we show that it is possible to relatively easily identify women at a very high risk of CVD,” Dr. Verkooijen said. “But what do we do with this information, because these scans are not made to answer this question. … This is information that we get that we haven’t really requested. I think we should only use this information when we have really shown that we can help patients reduce their risk of cardiovascular disease.”

To that end, Dr. Verkooijen and colleagues are planning additional research that will look at the potential benefit of referring high-risk patients for cardioprevention strategies and at the role of using the CAC score to personalize treatment strategies.

“This is an interesting and novel approach to predicting cardiac events for patients undergoing breast cancer treatment,” Meena S. Moran, MD, of Yale University in New Haven, Conn., commented in an interview.

The approach would likely be feasible in typical practice with widespread availability of the automated algorithm and might even alter treatment planning in real time, she said. “From the standpoint of radiation oncology, it would mean running the software to generate a CAC score, which would allow for modifications in decision-making during treatment planning, such as whether or not to include the internal mammary nodal chain in a patient who may be in the ‘gray zone’ for regional nodal radiation. For example, if a patient has a high CAC score, plus if they have received (or are receiving) cardiotoxic drugs, radiation oncologists can use that information as an additional factor to consider in the decision-making of whether or not to include the internal mammary chain, which inevitably can increase the dose delivered to the heart,” Dr. Moran elaborated.

Dr. Verkooijen’s study was supported by the Dutch Cancer Society, the European Commission, the Dutch Digestive Foundation, the Netherlands Organisation for Scientific Research, and Elekta. Dr. Verkooijen and Dr. Moran disclosed no conflicts of interest.

SOURCE: Gal R et al. EBCC-12 Virtual Congress, Abstract 7.

Radiotherapy planning scans may be a rich untapped source of information for estimating the risk of cardiovascular disease (CVD) in breast cancer patients, a large study suggests.

Photo courtesy of Ivar Pel

Researchers found that breast cancer patients with a coronary artery calcifications (CAC) score exceeding 400 had nearly four times the adjusted risk of fatal and nonfatal CVD events when compared with patients who had a CAC score of 0.

Patients with scores exceeding 400 also had more than eight times the risk of coronary heart disease events. The associations were especially strong in the subset of patients who received anthracycline-containing chemotherapy.

Helena Verkooijen, MD, PhD, of University Medical Center Utrecht (the Netherlands) presented these findings at the 12th European Breast Cancer Conference.

Dr. Verkooijen noted that, over the past 50 years, breast cancer has dramatically declined as a cause of death among breast cancer survivors, while CVD has continued to account for about 20% of the total deaths in this population.

CACs are sometimes incidentally seen in radiotherapy planning CT scans. “Right now, this information is not often used for patient stratification or informing patients about their cardiovascular risk, and this is a pity, because we know that it is an independent risk factor, and, often, the presence of calcifications can occur in the absence of other cardiovascular risk factors,” Dr. Verkooijen said.
 

Study details

Dr. Verkooijen and and colleagues from the Bragataston Study Group retrospectively studied 15,919 breast cancer patients who had radiotherapy planning CT scans during 2004-2016 at three Dutch institutions.

The researchers used an automated deep-learning algorithm (described in Radiology) to detect and quantify coronary calcium in planning CT scans and calculate CAC scores, classifying them into five categories.

The median follow-up was 51.6 months. Most women (70%) did not have any calcium detected in their coronary arteries (CAC score of 0), while 3% fell into the highest category (CAC score of >400).

The incidence of nonfatal and fatal CVD events increased with CAC score:

• 5.1% with a score of 0.
• 8.5% with a score of 1-10.
• 13.5% with a score of 11-100.
• 17.6% with a score of 101-400.
• 28.0% with a score greater than 400.

In analyses adjusted for age, laterality of radiation, and receipt of cardiotoxic agents – anthracyclines and trastuzumab – women with a score exceeding 400 had sharply elevated adjusted risks of CVD events (hazard ratio, 3.7), of coronary heart disease events specifically (HR, 8.2), and of death from any cause (HR, 2.8), when compared with peers who had a CAC score of 0.

On further scrutiny of CVD events, the pattern was similar regardless of whether radiation was left- or right-sided. However, the association was stronger among women who received anthracyclines as compared with counterparts who did not, with a nearly six-fold higher risk for those with highest versus lowest CAC scores.

When the women were surveyed, nearly 90% said they wanted to be informed about their CAC score and associated CVD risk, even in the absence of evidence-based risk reduction strategies.
 

Applying the results

“We believe that this is the first time that anyone has conducted a study on this topic on a scale like this, and we show that it is possible to relatively easily identify women at a very high risk of CVD,” Dr. Verkooijen said. “But what do we do with this information, because these scans are not made to answer this question. … This is information that we get that we haven’t really requested. I think we should only use this information when we have really shown that we can help patients reduce their risk of cardiovascular disease.”

To that end, Dr. Verkooijen and colleagues are planning additional research that will look at the potential benefit of referring high-risk patients for cardioprevention strategies and at the role of using the CAC score to personalize treatment strategies.

“This is an interesting and novel approach to predicting cardiac events for patients undergoing breast cancer treatment,” Meena S. Moran, MD, of Yale University in New Haven, Conn., commented in an interview.

The approach would likely be feasible in typical practice with widespread availability of the automated algorithm and might even alter treatment planning in real time, she said. “From the standpoint of radiation oncology, it would mean running the software to generate a CAC score, which would allow for modifications in decision-making during treatment planning, such as whether or not to include the internal mammary nodal chain in a patient who may be in the ‘gray zone’ for regional nodal radiation. For example, if a patient has a high CAC score, plus if they have received (or are receiving) cardiotoxic drugs, radiation oncologists can use that information as an additional factor to consider in the decision-making of whether or not to include the internal mammary chain, which inevitably can increase the dose delivered to the heart,” Dr. Moran elaborated.

Dr. Verkooijen’s study was supported by the Dutch Cancer Society, the European Commission, the Dutch Digestive Foundation, the Netherlands Organisation for Scientific Research, and Elekta. Dr. Verkooijen and Dr. Moran disclosed no conflicts of interest.

SOURCE: Gal R et al. EBCC-12 Virtual Congress, Abstract 7.

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

[email protected]

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

[email protected]

The latest drug shown to benefit patients with heart failure with reduced ejection fraction, the SGLT2 inhibitor empagliflozin, works just as well when added on top of a second major agent used to treat these patients, the renin-angiotensin system–inhibiting combination of sacubitril/valsartan, based on a post-hoc analysis of data from the EMPEROR-Reduced trial.

“When there are two very effective treatments, it’s common for people to ask: Which should I use?’ The goal of my presentation was to emphasize that the answer is both. We shouldn’t choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both,” said Milton Packer, MD at the virtual annual meeting of the Heart Failure Society of America.

EMPEROR-Reduced had the primary goal of testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in patients with heart failure with reduced ejection fraction (HFrEF). The results showed that adding this drug on top of standard treatments led to a 25% relative cut in the study’s primary efficacy endpoint, compared with placebo, and had this effect regardless of whether or not patients also had type 2 diabetes (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

Among the 3,730 patients enrolled in the trial, 727 (19%) were on sacubitril/valsartan (Entresto) at entry, which gave Dr. Packer the data to perform the analysis he reported. He presented the study’s three major endpoints as well as a quality of life analysis that compared the performance of empagliflozin in patients who were on sacubitril/valsartan at baseline with the other study patients, who were either on a different type of renin-angiotensin system (RAS) blocker (roughly 70% of study patients) or on no RAS inhibition (about 10% of patients).

The results showed no statistically significant indication of an interaction, suggesting that patients with sacubitril/valsartan on board had just as good response to empagliflozin as patients who were not on this combination. The landmark PARADIGM-HF trial proved several years ago that treatment of HFrEF patients with sacubitril/valsartan led to significantly better outcomes than did treatment with another form of RAS inhibition (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

For example, EMPEROR-Reduced’s primary endpoint, the combined rate of cardiovascular death or hospitalization for heart failure, fell by 36% relative to placebo in patients who received empagliflozin on top of sacubitril/valsartan, and by 23% relative to placebo among the remaining patients who received empagliflozin on top of a different type of RAS inhibitor drug or no RAS inhibition.

“Background treatment with sacubitril/valsartan did not diminish, and may have enhanced the efficacy of empagliflozin,” concluded Dr. Packer. Further analyses also showed that concurrent sacubitril/valsartan had no statistically significant impact on empagliflozin’s ability to reduce the rate of total heart failure hospitalizations, or to slow progressive loss of renal function, compared with placebo. The fourth efficacy analysis Dr. Packer presented showed that empagliflozin was also as effective for improving a quality-of-life measure in patients compared with placebo regardless of the type of RAS inhibition used. For all four outcomes, the point-estimate of empagliflozin’s benefit was higher when used along with sacubitril/valsartan.

Brian L. Claggett, PhD, a biostatistician at Brigham and Women’s Hospital and Harvard Medical School in Boston, designated discussant for the report, disagreed with Dr. Packer’s suggestion that the efficacy of empagliflozin may have been greater when administered against a background of sacubitril/valsartan. From a statistical perspective, there is no basis to suggest that patients did better when they were on both drugs, he cautioned. But Dr. Claggett acknowledged that the new analyses suggested that empagliflozin’s benefit wasn’t compromised by concurrent sacubitril/valsartan use. He also highlighted the value of more fully documenting the safety and efficacy of a new drug when used as part of “comprehensive therapy” with the established drugs that a patient may concurrently receive.

Dr. Packer also presented several measures of treatment safety that all showed similar rates of adverse effects between the empagliflozin and placebo recipients regardless of background RAS inhibition. A notable finding was that the incidence of hypokalemia was 5.9% in patients on empagliflozin and sacubitril/valsartan and 7.5% among patients on empagliflozin and a different type of RAS inhibition.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Claggett has been a consultant to Amgen, AO Biome, Biogen, Corvia, Myokardia, and Novartis.

[email protected]

Stroke may be the first presenting symptom of COVID-19 in younger patients, new research suggests. Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Although younger patients had the highest risk of stroke, the highest risk of death was in patients who were older, had other chronic conditions, and had more severe COVID-19–associated respiratory symptoms.

“One of the most eye-opening findings of this study is that, for patients under 50 years old, many were totally asymptomatic when they had a stroke related to COVID-19, [which] means that, for these patients, the stroke was their first symptom of the disease,” lead author Luciano Sposato, MD, MBA, associate professor and chair in stroke research at Western University, London, Ont.

The study was published online Sept. 15 in Neurology.
 

Anecdotal reports

“In early April of 2020, we realized that COVID-19 was a highly thrombogenic disease,” said Dr. Sposato. “Almost in parallel, I started to see anecdotal reports in social media of strokes occurring in patients with COVID-19, and there were also very few case reports.”

The investigators “thought it would be a good idea to put all the data together in one paper,” he said, and began by conducting a systematic review of 10 published studies of COVID-19 and stroke (n = 125 patients), which were then pooled with 35 unpublished cases from Canada, the United States, and Iran for a total of 160 cases.

The analysis examined in-hospital mortality rates of patients with stroke and COVID-19.

In addition, the researchers conducted a second review of 150 papers, encompassing a final cohort of 3,306 COVID-19 patients with stroke of any type and 5,322 with ischemic stroke.

“Some studies reported data for only ischemic stroke, and some reported data for all strokes considered together, which resulted in a different number of patients on each meta-analysis, with a lower number of ‘any stroke’ cases,” Dr. Sposato explained. “This review looked at the number of patients who developed a stroke during admission and included thousands of patients.”

Dr. Sposato noted that the first review was conducted on single case reports and small case series “to understand the clinical characteristics of strokes in patients with COVID-19 on an individual patient level,” since “large studies, including hundreds of thousands of patients, usually do not provide the level of detail for a descriptive analysis of the clinical characteristics of a disease.”

Cluster analyses were used to “identify specific clinical phenotypes and their relationship with death.” Patients were stratified into three age groups: <50, 50-70, and >70 years (“young,” “middle aged,” and “older,” respectively). The median age was 65 years and 43% were female.
 

Mortality ‘remarkably high’

The review showed that 1.8% (95% confidence interval, 0.9%-3.7%) of patients experienced a new stroke, while 1.5% (95% CI, 0.8%-2.8%) of these experienced an ischemic stroke. “These numbers are higher than historical data for other infectious diseases – for example, 0.75% in SARS-CoV-1, 0.78% in sepsis, and 0.2% in influenza,” Dr. Sposato commented.

Moreover, “this number may be an underestimate, given that many patients die without a confirmed diagnosis and that some patients did not come to the emergency department when experiencing mild symptoms during the first months of the pandemic,” he added.

Focusing on the review of 160 patients, the researchers described in-hospital mortality for strokes of all types and for ischemic strokes alone as “remarkably high” (34.4% [95% CI, 27.2%-42.4%] and 35.7% [95% CI, 27.5%-44.8%], respectively), with most deaths occurring among ischemic stroke patients.

“This high mortality rate is higher than the [roughly] 15% to 30% reported for stroke patients without COVID-19 admitted to intensive care units,” Dr. Sposato said.
 

High-risk phenotype

Many “young” COVID-19 patients (under age 50) who had a stroke (42.9%) had no previous risk factors or comorbidities. Moreover, in almost half of these patients (48.3%), stroke was more likely to occur before the onset of any COVID-19 respiratory symptoms.

Additionally, younger patients showed the highest frequency of elevated cardiac troponin compared with middle-aged and older patients (71.4% vs. 48.4% and 27.8%, respectively). On the other hand, mortality was 67% lower in younger versus older patients (odds ratio, 0.33; 95% CI, 0.12-0.94; P = .039).

Dr. Sposato noted that the proportion of ischemic stroke patients with large-vessel occlusion was “higher than previously reported” for patients with stroke without COVID-19 (47% compared with 29%, respectively).

“We should consider COVID-19 as a new cause or risk factor for stroke. At least, patients with stroke should probably be tested for SARS-CoV-2 infection if they are young and present with a large-vessel occlusion, even in the absence of typical COVID-19 respiratory symptoms,” he suggested.

The researchers identified a “high-risk phenotype” for death for all types of stroke considered together: older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms. Patients with all three characteristics had the highest in-hospital mortality rate (58.6%) and a threefold risk of death, compared with the rest of the cohort (OR, 3.52; 95% CI, 1.53-8.09; P = .003).

“Several potential mechanisms can explain the increased risk of stroke among COVID-19 patients, but perhaps the most important one is increased thrombogenesis secondary to an exaggerated inflammatory response,” Dr. Sposato said.
 

Not just elders

Commenting on the study, Jodi Edwards, PhD, director of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute, said the findings are “consistent with and underscore public health messaging emphasizing that COVID-19 does not only affect the elderly and those with underlying health conditions, but can have serious and even fatal consequences at any age.”

Dr. Edwards, who was not involved with the study, emphasized that “adherence to public health recommendations is critical to begin to reduce the rising incidence in younger adults.”

Dr. Sposato acknowledged that the study was small and that there “can be problems associated with a systematic review of case reports, such as publication bias, lack of completeness of data, etc, so more research is needed.”

Dr. Sposato is supported by the Kathleen & Dr. Henry Barnett Research Chair in Stroke Research at Western University, the Edward and Alma Saraydar Neurosciences Fund of the London Health Sciences Foundation, and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario. Dr. Sposato reported speaker honoraria from Boehringer Ingelheim, Pfizer, Gore, and Bayer and research/quality improvement grants from Boehringer Ingelheim and Bayer. The other authors’ disclosures are listed on the original article. Dr. Edwards has disclosed no relevant financial relationships.

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

Stroke may be the first presenting symptom of COVID-19 in younger patients, new research suggests. Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Although younger patients had the highest risk of stroke, the highest risk of death was in patients who were older, had other chronic conditions, and had more severe COVID-19–associated respiratory symptoms.

“One of the most eye-opening findings of this study is that, for patients under 50 years old, many were totally asymptomatic when they had a stroke related to COVID-19, [which] means that, for these patients, the stroke was their first symptom of the disease,” lead author Luciano Sposato, MD, MBA, associate professor and chair in stroke research at Western University, London, Ont.

The study was published online Sept. 15 in Neurology.
 

Anecdotal reports

“In early April of 2020, we realized that COVID-19 was a highly thrombogenic disease,” said Dr. Sposato. “Almost in parallel, I started to see anecdotal reports in social media of strokes occurring in patients with COVID-19, and there were also very few case reports.”

The investigators “thought it would be a good idea to put all the data together in one paper,” he said, and began by conducting a systematic review of 10 published studies of COVID-19 and stroke (n = 125 patients), which were then pooled with 35 unpublished cases from Canada, the United States, and Iran for a total of 160 cases.

The analysis examined in-hospital mortality rates of patients with stroke and COVID-19.

In addition, the researchers conducted a second review of 150 papers, encompassing a final cohort of 3,306 COVID-19 patients with stroke of any type and 5,322 with ischemic stroke.

“Some studies reported data for only ischemic stroke, and some reported data for all strokes considered together, which resulted in a different number of patients on each meta-analysis, with a lower number of ‘any stroke’ cases,” Dr. Sposato explained. “This review looked at the number of patients who developed a stroke during admission and included thousands of patients.”

Dr. Sposato noted that the first review was conducted on single case reports and small case series “to understand the clinical characteristics of strokes in patients with COVID-19 on an individual patient level,” since “large studies, including hundreds of thousands of patients, usually do not provide the level of detail for a descriptive analysis of the clinical characteristics of a disease.”

Cluster analyses were used to “identify specific clinical phenotypes and their relationship with death.” Patients were stratified into three age groups: <50, 50-70, and >70 years (“young,” “middle aged,” and “older,” respectively). The median age was 65 years and 43% were female.
 

Mortality ‘remarkably high’

The review showed that 1.8% (95% confidence interval, 0.9%-3.7%) of patients experienced a new stroke, while 1.5% (95% CI, 0.8%-2.8%) of these experienced an ischemic stroke. “These numbers are higher than historical data for other infectious diseases – for example, 0.75% in SARS-CoV-1, 0.78% in sepsis, and 0.2% in influenza,” Dr. Sposato commented.

Moreover, “this number may be an underestimate, given that many patients die without a confirmed diagnosis and that some patients did not come to the emergency department when experiencing mild symptoms during the first months of the pandemic,” he added.

Focusing on the review of 160 patients, the researchers described in-hospital mortality for strokes of all types and for ischemic strokes alone as “remarkably high” (34.4% [95% CI, 27.2%-42.4%] and 35.7% [95% CI, 27.5%-44.8%], respectively), with most deaths occurring among ischemic stroke patients.

“This high mortality rate is higher than the [roughly] 15% to 30% reported for stroke patients without COVID-19 admitted to intensive care units,” Dr. Sposato said.
 

High-risk phenotype

Many “young” COVID-19 patients (under age 50) who had a stroke (42.9%) had no previous risk factors or comorbidities. Moreover, in almost half of these patients (48.3%), stroke was more likely to occur before the onset of any COVID-19 respiratory symptoms.

Additionally, younger patients showed the highest frequency of elevated cardiac troponin compared with middle-aged and older patients (71.4% vs. 48.4% and 27.8%, respectively). On the other hand, mortality was 67% lower in younger versus older patients (odds ratio, 0.33; 95% CI, 0.12-0.94; P = .039).

Dr. Sposato noted that the proportion of ischemic stroke patients with large-vessel occlusion was “higher than previously reported” for patients with stroke without COVID-19 (47% compared with 29%, respectively).

“We should consider COVID-19 as a new cause or risk factor for stroke. At least, patients with stroke should probably be tested for SARS-CoV-2 infection if they are young and present with a large-vessel occlusion, even in the absence of typical COVID-19 respiratory symptoms,” he suggested.

The researchers identified a “high-risk phenotype” for death for all types of stroke considered together: older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms. Patients with all three characteristics had the highest in-hospital mortality rate (58.6%) and a threefold risk of death, compared with the rest of the cohort (OR, 3.52; 95% CI, 1.53-8.09; P = .003).

“Several potential mechanisms can explain the increased risk of stroke among COVID-19 patients, but perhaps the most important one is increased thrombogenesis secondary to an exaggerated inflammatory response,” Dr. Sposato said.
 

Not just elders

Commenting on the study, Jodi Edwards, PhD, director of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute, said the findings are “consistent with and underscore public health messaging emphasizing that COVID-19 does not only affect the elderly and those with underlying health conditions, but can have serious and even fatal consequences at any age.”

Dr. Edwards, who was not involved with the study, emphasized that “adherence to public health recommendations is critical to begin to reduce the rising incidence in younger adults.”

Dr. Sposato acknowledged that the study was small and that there “can be problems associated with a systematic review of case reports, such as publication bias, lack of completeness of data, etc, so more research is needed.”

Dr. Sposato is supported by the Kathleen & Dr. Henry Barnett Research Chair in Stroke Research at Western University, the Edward and Alma Saraydar Neurosciences Fund of the London Health Sciences Foundation, and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario. Dr. Sposato reported speaker honoraria from Boehringer Ingelheim, Pfizer, Gore, and Bayer and research/quality improvement grants from Boehringer Ingelheim and Bayer. The other authors’ disclosures are listed on the original article. Dr. Edwards has disclosed no relevant financial relationships.

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

Stroke may be the first presenting symptom of COVID-19 in younger patients, new research suggests. Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Although younger patients had the highest risk of stroke, the highest risk of death was in patients who were older, had other chronic conditions, and had more severe COVID-19–associated respiratory symptoms.

“One of the most eye-opening findings of this study is that, for patients under 50 years old, many were totally asymptomatic when they had a stroke related to COVID-19, [which] means that, for these patients, the stroke was their first symptom of the disease,” lead author Luciano Sposato, MD, MBA, associate professor and chair in stroke research at Western University, London, Ont.

The study was published online Sept. 15 in Neurology.
 

Anecdotal reports

“In early April of 2020, we realized that COVID-19 was a highly thrombogenic disease,” said Dr. Sposato. “Almost in parallel, I started to see anecdotal reports in social media of strokes occurring in patients with COVID-19, and there were also very few case reports.”

The investigators “thought it would be a good idea to put all the data together in one paper,” he said, and began by conducting a systematic review of 10 published studies of COVID-19 and stroke (n = 125 patients), which were then pooled with 35 unpublished cases from Canada, the United States, and Iran for a total of 160 cases.

The analysis examined in-hospital mortality rates of patients with stroke and COVID-19.

In addition, the researchers conducted a second review of 150 papers, encompassing a final cohort of 3,306 COVID-19 patients with stroke of any type and 5,322 with ischemic stroke.

“Some studies reported data for only ischemic stroke, and some reported data for all strokes considered together, which resulted in a different number of patients on each meta-analysis, with a lower number of ‘any stroke’ cases,” Dr. Sposato explained. “This review looked at the number of patients who developed a stroke during admission and included thousands of patients.”

Dr. Sposato noted that the first review was conducted on single case reports and small case series “to understand the clinical characteristics of strokes in patients with COVID-19 on an individual patient level,” since “large studies, including hundreds of thousands of patients, usually do not provide the level of detail for a descriptive analysis of the clinical characteristics of a disease.”

Cluster analyses were used to “identify specific clinical phenotypes and their relationship with death.” Patients were stratified into three age groups: <50, 50-70, and >70 years (“young,” “middle aged,” and “older,” respectively). The median age was 65 years and 43% were female.
 

Mortality ‘remarkably high’

The review showed that 1.8% (95% confidence interval, 0.9%-3.7%) of patients experienced a new stroke, while 1.5% (95% CI, 0.8%-2.8%) of these experienced an ischemic stroke. “These numbers are higher than historical data for other infectious diseases – for example, 0.75% in SARS-CoV-1, 0.78% in sepsis, and 0.2% in influenza,” Dr. Sposato commented.

Moreover, “this number may be an underestimate, given that many patients die without a confirmed diagnosis and that some patients did not come to the emergency department when experiencing mild symptoms during the first months of the pandemic,” he added.

Focusing on the review of 160 patients, the researchers described in-hospital mortality for strokes of all types and for ischemic strokes alone as “remarkably high” (34.4% [95% CI, 27.2%-42.4%] and 35.7% [95% CI, 27.5%-44.8%], respectively), with most deaths occurring among ischemic stroke patients.

“This high mortality rate is higher than the [roughly] 15% to 30% reported for stroke patients without COVID-19 admitted to intensive care units,” Dr. Sposato said.
 

High-risk phenotype

Many “young” COVID-19 patients (under age 50) who had a stroke (42.9%) had no previous risk factors or comorbidities. Moreover, in almost half of these patients (48.3%), stroke was more likely to occur before the onset of any COVID-19 respiratory symptoms.

Additionally, younger patients showed the highest frequency of elevated cardiac troponin compared with middle-aged and older patients (71.4% vs. 48.4% and 27.8%, respectively). On the other hand, mortality was 67% lower in younger versus older patients (odds ratio, 0.33; 95% CI, 0.12-0.94; P = .039).

Dr. Sposato noted that the proportion of ischemic stroke patients with large-vessel occlusion was “higher than previously reported” for patients with stroke without COVID-19 (47% compared with 29%, respectively).

“We should consider COVID-19 as a new cause or risk factor for stroke. At least, patients with stroke should probably be tested for SARS-CoV-2 infection if they are young and present with a large-vessel occlusion, even in the absence of typical COVID-19 respiratory symptoms,” he suggested.

The researchers identified a “high-risk phenotype” for death for all types of stroke considered together: older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms. Patients with all three characteristics had the highest in-hospital mortality rate (58.6%) and a threefold risk of death, compared with the rest of the cohort (OR, 3.52; 95% CI, 1.53-8.09; P = .003).

“Several potential mechanisms can explain the increased risk of stroke among COVID-19 patients, but perhaps the most important one is increased thrombogenesis secondary to an exaggerated inflammatory response,” Dr. Sposato said.
 

Not just elders

Commenting on the study, Jodi Edwards, PhD, director of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute, said the findings are “consistent with and underscore public health messaging emphasizing that COVID-19 does not only affect the elderly and those with underlying health conditions, but can have serious and even fatal consequences at any age.”

Dr. Edwards, who was not involved with the study, emphasized that “adherence to public health recommendations is critical to begin to reduce the rising incidence in younger adults.”

Dr. Sposato acknowledged that the study was small and that there “can be problems associated with a systematic review of case reports, such as publication bias, lack of completeness of data, etc, so more research is needed.”

Dr. Sposato is supported by the Kathleen & Dr. Henry Barnett Research Chair in Stroke Research at Western University, the Edward and Alma Saraydar Neurosciences Fund of the London Health Sciences Foundation, and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario. Dr. Sposato reported speaker honoraria from Boehringer Ingelheim, Pfizer, Gore, and Bayer and research/quality improvement grants from Boehringer Ingelheim and Bayer. The other authors’ disclosures are listed on the original article. Dr. Edwards has disclosed no relevant financial relationships.

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

The Centers for Disease Control and Prevention acknowledged Oct. 5 in updated guidance that COVID-19 can sometimes be spread through the air, especially in enclosed spaces with poor ventilation, when people are more than 6 feet apart.

The information reiterates, however, that “COVID-19 is thought to spread mainly through close contact from person to person, including between people who are physically near each other (within about 6 feet). People who are infected but do not show symptoms can also spread the virus to others.”

In a statement to the media, the CDC said, “Today’s update acknowledges the existence of some published reports showing limited, uncommon circumstances where people with COVID-19 infected others who were more than 6 feet away or shortly after the COVID-19–positive person left an area. In these instances, transmission occurred in poorly ventilated and enclosed spaces that often involved activities that caused heavier breathing, like singing or exercise. Such environments and activities may contribute to the buildup of virus-carrying particles.”

“This is HUGE and been long delayed. But glad it’s now CDC official,” tweeted Eric Feigl-Ding, MD, an epidemiologist and health economist at Harvard University, Boston on Oct. 5.

The CDC announcement follows an abrupt flip-flop on information last month surrounding the aerosol spread of the virus.
 

Information deleted from website last month

On September 18, the CDC had added to its existing guidance that the virus is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection.”

The CDC then deleted that guidance on Sept. 21, saying it was a draft update released in error.

A key element of the now-deleted guidance said, “this is thought to be the main way the virus spreads.”

The information updated today reverses the now-deleted guidance and says aerosol transmission is not the main way the virus spreads.

It states that people who are within 6 feet of a person with COVID-19 or have direct contact with that person have the greatest risk of infection.

The CDC reiterated in the statement to the media today, “People can protect themselves from the virus that causes COVID-19 by staying at least 6 feet away from others, wearing a mask that covers their nose and mouth, washing their hands frequently, cleaning touched surfaces often, and staying home when sick.”

Among the journals that have published evidence on aerosol spread is Clinical Infectious Diseases, which, on July 6, published the paper, “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors wrote, “there is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).”

Aerosols and airborne transmission “are the only way to explain super-spreader events we are seeing,” said Kimberly Prather, PhD, an atmospheric chemist at the University of California at San Diego, in an interview Oct. 5 with the Washington Post.

Dr. Prather added that, once aerosolization is acknowledged, this becomes a “fixable” problem through proper ventilation.

“Wear masks at all times indoors when others are present,” Dr. Prather said. But when inside, she said, there’s no such thing as a completely safe social distance.

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention acknowledged Oct. 5 in updated guidance that COVID-19 can sometimes be spread through the air, especially in enclosed spaces with poor ventilation, when people are more than 6 feet apart.

The information reiterates, however, that “COVID-19 is thought to spread mainly through close contact from person to person, including between people who are physically near each other (within about 6 feet). People who are infected but do not show symptoms can also spread the virus to others.”

In a statement to the media, the CDC said, “Today’s update acknowledges the existence of some published reports showing limited, uncommon circumstances where people with COVID-19 infected others who were more than 6 feet away or shortly after the COVID-19–positive person left an area. In these instances, transmission occurred in poorly ventilated and enclosed spaces that often involved activities that caused heavier breathing, like singing or exercise. Such environments and activities may contribute to the buildup of virus-carrying particles.”

“This is HUGE and been long delayed. But glad it’s now CDC official,” tweeted Eric Feigl-Ding, MD, an epidemiologist and health economist at Harvard University, Boston on Oct. 5.

The CDC announcement follows an abrupt flip-flop on information last month surrounding the aerosol spread of the virus.
 

Information deleted from website last month

On September 18, the CDC had added to its existing guidance that the virus is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection.”

The CDC then deleted that guidance on Sept. 21, saying it was a draft update released in error.

A key element of the now-deleted guidance said, “this is thought to be the main way the virus spreads.”

The information updated today reverses the now-deleted guidance and says aerosol transmission is not the main way the virus spreads.

It states that people who are within 6 feet of a person with COVID-19 or have direct contact with that person have the greatest risk of infection.

The CDC reiterated in the statement to the media today, “People can protect themselves from the virus that causes COVID-19 by staying at least 6 feet away from others, wearing a mask that covers their nose and mouth, washing their hands frequently, cleaning touched surfaces often, and staying home when sick.”

Among the journals that have published evidence on aerosol spread is Clinical Infectious Diseases, which, on July 6, published the paper, “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors wrote, “there is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).”

Aerosols and airborne transmission “are the only way to explain super-spreader events we are seeing,” said Kimberly Prather, PhD, an atmospheric chemist at the University of California at San Diego, in an interview Oct. 5 with the Washington Post.

Dr. Prather added that, once aerosolization is acknowledged, this becomes a “fixable” problem through proper ventilation.

“Wear masks at all times indoors when others are present,” Dr. Prather said. But when inside, she said, there’s no such thing as a completely safe social distance.

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention acknowledged Oct. 5 in updated guidance that COVID-19 can sometimes be spread through the air, especially in enclosed spaces with poor ventilation, when people are more than 6 feet apart.

The information reiterates, however, that “COVID-19 is thought to spread mainly through close contact from person to person, including between people who are physically near each other (within about 6 feet). People who are infected but do not show symptoms can also spread the virus to others.”

In a statement to the media, the CDC said, “Today’s update acknowledges the existence of some published reports showing limited, uncommon circumstances where people with COVID-19 infected others who were more than 6 feet away or shortly after the COVID-19–positive person left an area. In these instances, transmission occurred in poorly ventilated and enclosed spaces that often involved activities that caused heavier breathing, like singing or exercise. Such environments and activities may contribute to the buildup of virus-carrying particles.”

“This is HUGE and been long delayed. But glad it’s now CDC official,” tweeted Eric Feigl-Ding, MD, an epidemiologist and health economist at Harvard University, Boston on Oct. 5.

The CDC announcement follows an abrupt flip-flop on information last month surrounding the aerosol spread of the virus.
 

Information deleted from website last month

On September 18, the CDC had added to its existing guidance that the virus is spread “through respiratory droplets or small particles, such as those in aerosols, produced when an infected person coughs, sneezes, sings, talks, or breathes. These particles can be inhaled into the nose, mouth, airways, and lungs and cause infection.”

The CDC then deleted that guidance on Sept. 21, saying it was a draft update released in error.

A key element of the now-deleted guidance said, “this is thought to be the main way the virus spreads.”

The information updated today reverses the now-deleted guidance and says aerosol transmission is not the main way the virus spreads.

It states that people who are within 6 feet of a person with COVID-19 or have direct contact with that person have the greatest risk of infection.

The CDC reiterated in the statement to the media today, “People can protect themselves from the virus that causes COVID-19 by staying at least 6 feet away from others, wearing a mask that covers their nose and mouth, washing their hands frequently, cleaning touched surfaces often, and staying home when sick.”

Among the journals that have published evidence on aerosol spread is Clinical Infectious Diseases, which, on July 6, published the paper, “It Is Time to Address Airborne Transmission of Coronavirus Disease 2019,” which was supported by 239 scientists.

The authors wrote, “there is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale).”

Aerosols and airborne transmission “are the only way to explain super-spreader events we are seeing,” said Kimberly Prather, PhD, an atmospheric chemist at the University of California at San Diego, in an interview Oct. 5 with the Washington Post.

Dr. Prather added that, once aerosolization is acknowledged, this becomes a “fixable” problem through proper ventilation.

“Wear masks at all times indoors when others are present,” Dr. Prather said. But when inside, she said, there’s no such thing as a completely safe social distance.

This article first appeared on Medscape.com.

Black and Hispanic children comprised significantly more cases of COVID-19, compared with White children, based on data from a large, cross-sectional study of 1,000 cases.

“Data regarding disparities in SARS-CoV-2 infection and outcomes have been, thus far, mostly limited to adults,” wrote Monika K. Goyal, MD, of Children’s National Hospital, Washington, and colleagues. “Additional data further suggest that low socioeconomic status may further exacerbate health outcomes for racial and ethnic minorities.”

In a study published in Pediatrics, the researchers conducted a cross-sectional analysis of 1,000 children from a registry of non–acutely ill pediatric patients seen at a drive-through and walk-up COVID-19 test site.
 

Minority, socioeconomic status affect pediatric outcomes too

Overall, 207 (21%) of the children tested positive for COVID-19; of these 46% were Hispanic, 30% were non-Hispanic Black, and 7% were non-Hispanic White. The median age of the study population was 8 years, and approximately half were male.

The researchers also examined the association of median family income (MFI) using census block group estimates data from the American Community Survey (2014–2018) to represent socioeconomic status.

Infection rates were significantly higher among children in the lowest three quartiles of MFI (24%, 27%, and 38% for quartiles 3, 2, and 1, respectively), compared with the highest quartile of MFI (9%).

After adjusting for age, sex, and MFI, Hispanic children were six times more likely and non-Hispanic Black children were twice as likely to test positive for COVID-19 than non-Hispanic White children (adjusted odds ratios, 6.3 and 2.3, respectively).

The study findings were limited by several factors including the use of clinician-reported ethnicity and thus potential for misclassification, the researchers noted. In addition, the socioeconomic and racial disparities may be underestimated because these groups have less access to primary care, and the study did not allow for confounding variables including housing conditions or occupancy.

“Although it was beyond the scope of this study to understand the causes for these differential rates of infection, the causes may be multifactorial, including, but not limited to, structural factors, poorer access to health care, limited resources, and bias and discrimination,” the researchers noted. In addition, the high infection rate among minority children may be impacted by parents who are less able to telework, find child care, or avoid public transportation, Dr. Goyal and associates wrote.

Future research should address “the modifiable reasons for these observed disparities as well as their differential impact in terms of SARS-CoV-2–related morbidity and mortality outcomes to mitigate the spread of infection and its health effects,” they concluded.
 

How to help

“This study is important because we need to understand which groups of children are at highest risk for SARS-CoV-2 infection in order to maximize efforts for screening, allocating resources, and prioritizing vaccine administration,” Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was not surprised at the higher infection rates in general in minorities and low socioeconomic groups. “We already knew that adult COVID-19 rates were higher for people in certain racial/ethnic groups and those with socioeconomic disadvantages; however, I was shocked by the percentages. That is a huge burden for a population that already has disparities in health outcomes.”

“As the authors cite, this was not a research study of why these groups were more likely to be COVID-19 positive, but they speculated that crowded living conditions, multigenerational families living together, and many minorities being essential workers unable to work from home,” said Dr. Kinsella. Additional factors contributing to higher infection rates may include limited access to care, transportation issues, insurance coverage, schedule challenges, and fear of deportation. Some of these problems might be addressed by coming into communities in mobile vans, visiting community health centers and schools with free educational materials, using masks and hand sanitizer, and offering free access to testing.

“Future studies could confirm the cause of this discrepancy, as well as study community-based interventions and their outcomes,” Dr. Kinsella said. In the meantime, a take-home message for clinicians is the need to prioritize screening, resources, and vaccines to reflect the higher rates of SARS-CoV-2 infections in children from disadvantaged racial and socioeconomic backgrounds.

The study received no outside funding. The researchers had no financial conflicts to disclose, but lead author Dr. Goyal is a member of the Pediatrics editorial board. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News editorial advisory board.

SOURCE: Goyal MK et al. Pediatrics. 2020 Sep 24. doi: 10.1542/peds.2020-009951.

Black and Hispanic children comprised significantly more cases of COVID-19, compared with White children, based on data from a large, cross-sectional study of 1,000 cases.

“Data regarding disparities in SARS-CoV-2 infection and outcomes have been, thus far, mostly limited to adults,” wrote Monika K. Goyal, MD, of Children’s National Hospital, Washington, and colleagues. “Additional data further suggest that low socioeconomic status may further exacerbate health outcomes for racial and ethnic minorities.”

In a study published in Pediatrics, the researchers conducted a cross-sectional analysis of 1,000 children from a registry of non–acutely ill pediatric patients seen at a drive-through and walk-up COVID-19 test site.
 

Minority, socioeconomic status affect pediatric outcomes too

Overall, 207 (21%) of the children tested positive for COVID-19; of these 46% were Hispanic, 30% were non-Hispanic Black, and 7% were non-Hispanic White. The median age of the study population was 8 years, and approximately half were male.

The researchers also examined the association of median family income (MFI) using census block group estimates data from the American Community Survey (2014–2018) to represent socioeconomic status.

Infection rates were significantly higher among children in the lowest three quartiles of MFI (24%, 27%, and 38% for quartiles 3, 2, and 1, respectively), compared with the highest quartile of MFI (9%).

After adjusting for age, sex, and MFI, Hispanic children were six times more likely and non-Hispanic Black children were twice as likely to test positive for COVID-19 than non-Hispanic White children (adjusted odds ratios, 6.3 and 2.3, respectively).

The study findings were limited by several factors including the use of clinician-reported ethnicity and thus potential for misclassification, the researchers noted. In addition, the socioeconomic and racial disparities may be underestimated because these groups have less access to primary care, and the study did not allow for confounding variables including housing conditions or occupancy.

“Although it was beyond the scope of this study to understand the causes for these differential rates of infection, the causes may be multifactorial, including, but not limited to, structural factors, poorer access to health care, limited resources, and bias and discrimination,” the researchers noted. In addition, the high infection rate among minority children may be impacted by parents who are less able to telework, find child care, or avoid public transportation, Dr. Goyal and associates wrote.

Future research should address “the modifiable reasons for these observed disparities as well as their differential impact in terms of SARS-CoV-2–related morbidity and mortality outcomes to mitigate the spread of infection and its health effects,” they concluded.
 

How to help

“This study is important because we need to understand which groups of children are at highest risk for SARS-CoV-2 infection in order to maximize efforts for screening, allocating resources, and prioritizing vaccine administration,” Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was not surprised at the higher infection rates in general in minorities and low socioeconomic groups. “We already knew that adult COVID-19 rates were higher for people in certain racial/ethnic groups and those with socioeconomic disadvantages; however, I was shocked by the percentages. That is a huge burden for a population that already has disparities in health outcomes.”

“As the authors cite, this was not a research study of why these groups were more likely to be COVID-19 positive, but they speculated that crowded living conditions, multigenerational families living together, and many minorities being essential workers unable to work from home,” said Dr. Kinsella. Additional factors contributing to higher infection rates may include limited access to care, transportation issues, insurance coverage, schedule challenges, and fear of deportation. Some of these problems might be addressed by coming into communities in mobile vans, visiting community health centers and schools with free educational materials, using masks and hand sanitizer, and offering free access to testing.

“Future studies could confirm the cause of this discrepancy, as well as study community-based interventions and their outcomes,” Dr. Kinsella said. In the meantime, a take-home message for clinicians is the need to prioritize screening, resources, and vaccines to reflect the higher rates of SARS-CoV-2 infections in children from disadvantaged racial and socioeconomic backgrounds.

The study received no outside funding. The researchers had no financial conflicts to disclose, but lead author Dr. Goyal is a member of the Pediatrics editorial board. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News editorial advisory board.

SOURCE: Goyal MK et al. Pediatrics. 2020 Sep 24. doi: 10.1542/peds.2020-009951.

Black and Hispanic children comprised significantly more cases of COVID-19, compared with White children, based on data from a large, cross-sectional study of 1,000 cases.

“Data regarding disparities in SARS-CoV-2 infection and outcomes have been, thus far, mostly limited to adults,” wrote Monika K. Goyal, MD, of Children’s National Hospital, Washington, and colleagues. “Additional data further suggest that low socioeconomic status may further exacerbate health outcomes for racial and ethnic minorities.”

In a study published in Pediatrics, the researchers conducted a cross-sectional analysis of 1,000 children from a registry of non–acutely ill pediatric patients seen at a drive-through and walk-up COVID-19 test site.
 

Minority, socioeconomic status affect pediatric outcomes too

Overall, 207 (21%) of the children tested positive for COVID-19; of these 46% were Hispanic, 30% were non-Hispanic Black, and 7% were non-Hispanic White. The median age of the study population was 8 years, and approximately half were male.

The researchers also examined the association of median family income (MFI) using census block group estimates data from the American Community Survey (2014–2018) to represent socioeconomic status.

Infection rates were significantly higher among children in the lowest three quartiles of MFI (24%, 27%, and 38% for quartiles 3, 2, and 1, respectively), compared with the highest quartile of MFI (9%).

After adjusting for age, sex, and MFI, Hispanic children were six times more likely and non-Hispanic Black children were twice as likely to test positive for COVID-19 than non-Hispanic White children (adjusted odds ratios, 6.3 and 2.3, respectively).

The study findings were limited by several factors including the use of clinician-reported ethnicity and thus potential for misclassification, the researchers noted. In addition, the socioeconomic and racial disparities may be underestimated because these groups have less access to primary care, and the study did not allow for confounding variables including housing conditions or occupancy.

“Although it was beyond the scope of this study to understand the causes for these differential rates of infection, the causes may be multifactorial, including, but not limited to, structural factors, poorer access to health care, limited resources, and bias and discrimination,” the researchers noted. In addition, the high infection rate among minority children may be impacted by parents who are less able to telework, find child care, or avoid public transportation, Dr. Goyal and associates wrote.

Future research should address “the modifiable reasons for these observed disparities as well as their differential impact in terms of SARS-CoV-2–related morbidity and mortality outcomes to mitigate the spread of infection and its health effects,” they concluded.
 

How to help

“This study is important because we need to understand which groups of children are at highest risk for SARS-CoV-2 infection in order to maximize efforts for screening, allocating resources, and prioritizing vaccine administration,” Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was not surprised at the higher infection rates in general in minorities and low socioeconomic groups. “We already knew that adult COVID-19 rates were higher for people in certain racial/ethnic groups and those with socioeconomic disadvantages; however, I was shocked by the percentages. That is a huge burden for a population that already has disparities in health outcomes.”

“As the authors cite, this was not a research study of why these groups were more likely to be COVID-19 positive, but they speculated that crowded living conditions, multigenerational families living together, and many minorities being essential workers unable to work from home,” said Dr. Kinsella. Additional factors contributing to higher infection rates may include limited access to care, transportation issues, insurance coverage, schedule challenges, and fear of deportation. Some of these problems might be addressed by coming into communities in mobile vans, visiting community health centers and schools with free educational materials, using masks and hand sanitizer, and offering free access to testing.

“Future studies could confirm the cause of this discrepancy, as well as study community-based interventions and their outcomes,” Dr. Kinsella said. In the meantime, a take-home message for clinicians is the need to prioritize screening, resources, and vaccines to reflect the higher rates of SARS-CoV-2 infections in children from disadvantaged racial and socioeconomic backgrounds.

The study received no outside funding. The researchers had no financial conflicts to disclose, but lead author Dr. Goyal is a member of the Pediatrics editorial board. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News editorial advisory board.

SOURCE: Goyal MK et al. Pediatrics. 2020 Sep 24. doi: 10.1542/peds.2020-009951.

Parents who did not vaccinate their children against influenza last year were significantly less likely to do so this year than parents whose children were vaccinated last year, based on survey data from more than 2,000 parents with babies and young children.

Choreograph/Thinkstock

“Pediatric vaccination will be an important component to mitigating a dual influenza/COVID-19 epidemic,” Rebeccah L. Sokol, PhD, of Wayne State University, Detroit, and Anna H. Grummon, PhD, of Harvard School of Public Health, Boston, reported in Pediatrics.

Although the pandemic has increased acceptance of some healthy behaviors including handwashing and social distancing, the impact on influenza vaccination rates remains unknown, they said.

To assess parents’ current intentions for flu vaccination of young children this season, the researchers conducted an online survey of 2,164 parents or guardians of children aged between 6 months and 5 years in the United States. The 15-minute online survey was conducted in May 2020 and participants received gift cards. The primary outcome was the impact of the COVID-19 pandemic on parental intentions for having their child vaccinated against seasonal flu this year.

“We measured change categorically, with response options ranging from 1 (I became much less likely to get my child the flu shot next year) to 5 (I became much more likely to get my child the flu shot next year),” the researchers said.
 

Pandemic changes some parents’ plans

Overall, 60% of parents said that the ongoing pandemic had altered their flu vaccination intentions for their children. About 34% percent of parents whose children did not receive flu vaccine last year said they would not seek the vaccine this year because of the pandemic, compared with 25% of parents whose children received last year’s flu vaccine, a statistically significant difference (P < .001).

Approximately 21% of parents whose children received no flu vaccine last year said the pandemic made them more likely to seek vaccination for the 2020-2021 season, compared with 38% of parents whose children received last year’s flu vaccine.

“These results suggest that overall seasonal influenza vaccination rates may not increase simply because of an ongoing infectious disease pandemic. Instead, a significant predictor of future behavior remains past behavior,” Dr. Sokol and Dr. Grummon said.

The study findings were limited by several factors including the use of a convenience sample and the timing of the survey in May 2020, meaning that survey results might not be generalizable this fall as the pandemic persists, they noted. “Additionally, we assessed intentions to vaccinate; future research will clarify the COVID-19 pandemic’s influence on actual vaccination behaviors.”

The challenge of how to increase uptake of the influenza vaccine during the era of COVID-19 remains, and targeted efforts could include social norms messaging through social media, mass media, or health care providers to increase parents’ intentions to vaccinate, as well as vaccination reminders and presumptive announcements from health care providers that present vaccination as the default option, the researchers added.
 

Potential for ‘twindemic’ is real

The uptake of flu vaccination is especially important this year, Christopher J. Harrison, MD, director of the vaccine and treatment evaluation unit and professor of pediatrics at the University of Missouri–Kansas City, said in an interview.

“This year we are entering a flu season where the certainty of the timing as well as the potential severity of the season are not known. That said, social distancing and wearing masks – to the extent that enough people conform to COVID-19 precautions – could delay or even blunt the usual influenza season,” he noted.

Unfortunately, the Centers for Disease Control and Prevention and the Food and Drug Administration have had their credibility damaged by the challenges of creating a successful response on the fly to a uniquely multifaceted virus to which previous rules do not apply, Dr. Harrison said. In addition, public confidence was eroded when information about testing and reopening policies were released by non-CDC nonscientists and labeled “CDC recommended,” with no opportunity for the scientific community to correct inaccuracies.

“The current study reveals that public trust in influenza vaccine and indirectly in health authorities has been affected by the pandemic,” said Dr. Harrison. “Vaccine hesitancy has increased somewhat even among previous vaccine accepters. One wonders if promises of a quick COVID-19 vaccine increased mistrust of the FDA because of safety concerns, even among the most ardent provaccine population, and whether these concerns are bleeding over into influenza vaccine concerns.

“This only adds to the anxiety that families feel about visiting any medical facility for routine vaccines while the pandemic rages, and we now are in a fall SARS-CoV-2 resurgence,” he added.

Although the current study data are concerning, “there could still be a net gain of pediatric influenza vaccine uptake this season because the 34% less likely to immunize among previously nonimmunizing families would be counterbalanced by 21% of the same group being more likely to immunize their children [theoretical net loss of 13%],” Dr. Harrison explained. “But the pandemic seems to have motivated previously influenza-immunizing families, i.e. while 24% were less likely, 39% are more likely to immunize [theoretical net gain of 15%]. That said, we would still be way short of the number needed to get to herd immunity.”

Dr. Harrison said he found the findings somewhat surprising, but perhaps he should not have. “I had hoped for more acceptance rather than most people staying in their prior vaccine ‘opinion lanes,’ ending up with likely little overall net change in plans to immunize despite increased health awareness caused by a pandemic.”

However, “the U.S. population has been polarized on vaccines and particularly influenza vaccines for more than 50 years, so why would a pandemic make us less polarized, particularly when the pandemic itself has been a polarizing event?” he questioned.

The greatest barriers to flu vaccination for children this year include a lack of motivation among families to visit immunization sites, given the ongoing need for social distancing and masks, Dr. Harrison said.

“Another barrier is the waning public confidence in our medical/scientific national leaders and organizations,” he emphasized. “This makes it crucial that primary care providers step up and be extra strong vaccine advocates, despite the fact that pandemic economics and necessary safety processes have stressed providers and devastated practices. Indeed, in times of medical stress, no one gets more trust from families than their own personal provider.”

Ultimately, avenues for future research include asking diverse groups of families what they feel they need to hear to be more engaged in immunizing children against influenza. But for now, the current study findings identify that “the public is not uniformly responding to the pandemic’s influence on their likelihood of immunizing their children against influenza,” Dr. Harrison said.

“We now know the size of the problem and hopefully governments, public health organizations, pediatric advocates and clinical care givers can find ways to magnify the message that a pandemic year is not a year to avoid seasonal influenza vaccine unless one has a true contraindication,” Dr. Harrison said.

In addition, “one wonders if the poll were taken today – post the president’s COVID-19 illness – would the answers be different?” he noted.

Dr. Sokol’s work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development but otherwise had no financial conflicts to disclose. Dr. Harrison disclosed that his institution receives grant funding from Merck, Pfizer, and GlaxoSmithKline for pediatric noninfluenza vaccine studies on which he is a subinvestigator, and support from the CDC for pediatric respiratory and gastrointestinal virus surveillance studies on which he is an investigator.

SOURCE: Sokol RL, Grummon AH. Pediatrics. 2020 Sep 30. doi: 10.1542/peds.2020-022871.

Parents who did not vaccinate their children against influenza last year were significantly less likely to do so this year than parents whose children were vaccinated last year, based on survey data from more than 2,000 parents with babies and young children.

Choreograph/Thinkstock

“Pediatric vaccination will be an important component to mitigating a dual influenza/COVID-19 epidemic,” Rebeccah L. Sokol, PhD, of Wayne State University, Detroit, and Anna H. Grummon, PhD, of Harvard School of Public Health, Boston, reported in Pediatrics.

Although the pandemic has increased acceptance of some healthy behaviors including handwashing and social distancing, the impact on influenza vaccination rates remains unknown, they said.

To assess parents’ current intentions for flu vaccination of young children this season, the researchers conducted an online survey of 2,164 parents or guardians of children aged between 6 months and 5 years in the United States. The 15-minute online survey was conducted in May 2020 and participants received gift cards. The primary outcome was the impact of the COVID-19 pandemic on parental intentions for having their child vaccinated against seasonal flu this year.

“We measured change categorically, with response options ranging from 1 (I became much less likely to get my child the flu shot next year) to 5 (I became much more likely to get my child the flu shot next year),” the researchers said.
 

Pandemic changes some parents’ plans

Overall, 60% of parents said that the ongoing pandemic had altered their flu vaccination intentions for their children. About 34% percent of parents whose children did not receive flu vaccine last year said they would not seek the vaccine this year because of the pandemic, compared with 25% of parents whose children received last year’s flu vaccine, a statistically significant difference (P < .001).

Approximately 21% of parents whose children received no flu vaccine last year said the pandemic made them more likely to seek vaccination for the 2020-2021 season, compared with 38% of parents whose children received last year’s flu vaccine.

“These results suggest that overall seasonal influenza vaccination rates may not increase simply because of an ongoing infectious disease pandemic. Instead, a significant predictor of future behavior remains past behavior,” Dr. Sokol and Dr. Grummon said.

The study findings were limited by several factors including the use of a convenience sample and the timing of the survey in May 2020, meaning that survey results might not be generalizable this fall as the pandemic persists, they noted. “Additionally, we assessed intentions to vaccinate; future research will clarify the COVID-19 pandemic’s influence on actual vaccination behaviors.”

The challenge of how to increase uptake of the influenza vaccine during the era of COVID-19 remains, and targeted efforts could include social norms messaging through social media, mass media, or health care providers to increase parents’ intentions to vaccinate, as well as vaccination reminders and presumptive announcements from health care providers that present vaccination as the default option, the researchers added.
 

Potential for ‘twindemic’ is real

The uptake of flu vaccination is especially important this year, Christopher J. Harrison, MD, director of the vaccine and treatment evaluation unit and professor of pediatrics at the University of Missouri–Kansas City, said in an interview.

“This year we are entering a flu season where the certainty of the timing as well as the potential severity of the season are not known. That said, social distancing and wearing masks – to the extent that enough people conform to COVID-19 precautions – could delay or even blunt the usual influenza season,” he noted.

Unfortunately, the Centers for Disease Control and Prevention and the Food and Drug Administration have had their credibility damaged by the challenges of creating a successful response on the fly to a uniquely multifaceted virus to which previous rules do not apply, Dr. Harrison said. In addition, public confidence was eroded when information about testing and reopening policies were released by non-CDC nonscientists and labeled “CDC recommended,” with no opportunity for the scientific community to correct inaccuracies.

“The current study reveals that public trust in influenza vaccine and indirectly in health authorities has been affected by the pandemic,” said Dr. Harrison. “Vaccine hesitancy has increased somewhat even among previous vaccine accepters. One wonders if promises of a quick COVID-19 vaccine increased mistrust of the FDA because of safety concerns, even among the most ardent provaccine population, and whether these concerns are bleeding over into influenza vaccine concerns.

“This only adds to the anxiety that families feel about visiting any medical facility for routine vaccines while the pandemic rages, and we now are in a fall SARS-CoV-2 resurgence,” he added.

Although the current study data are concerning, “there could still be a net gain of pediatric influenza vaccine uptake this season because the 34% less likely to immunize among previously nonimmunizing families would be counterbalanced by 21% of the same group being more likely to immunize their children [theoretical net loss of 13%],” Dr. Harrison explained. “But the pandemic seems to have motivated previously influenza-immunizing families, i.e. while 24% were less likely, 39% are more likely to immunize [theoretical net gain of 15%]. That said, we would still be way short of the number needed to get to herd immunity.”

Dr. Harrison said he found the findings somewhat surprising, but perhaps he should not have. “I had hoped for more acceptance rather than most people staying in their prior vaccine ‘opinion lanes,’ ending up with likely little overall net change in plans to immunize despite increased health awareness caused by a pandemic.”

However, “the U.S. population has been polarized on vaccines and particularly influenza vaccines for more than 50 years, so why would a pandemic make us less polarized, particularly when the pandemic itself has been a polarizing event?” he questioned.

The greatest barriers to flu vaccination for children this year include a lack of motivation among families to visit immunization sites, given the ongoing need for social distancing and masks, Dr. Harrison said.

“Another barrier is the waning public confidence in our medical/scientific national leaders and organizations,” he emphasized. “This makes it crucial that primary care providers step up and be extra strong vaccine advocates, despite the fact that pandemic economics and necessary safety processes have stressed providers and devastated practices. Indeed, in times of medical stress, no one gets more trust from families than their own personal provider.”

Ultimately, avenues for future research include asking diverse groups of families what they feel they need to hear to be more engaged in immunizing children against influenza. But for now, the current study findings identify that “the public is not uniformly responding to the pandemic’s influence on their likelihood of immunizing their children against influenza,” Dr. Harrison said.

“We now know the size of the problem and hopefully governments, public health organizations, pediatric advocates and clinical care givers can find ways to magnify the message that a pandemic year is not a year to avoid seasonal influenza vaccine unless one has a true contraindication,” Dr. Harrison said.

In addition, “one wonders if the poll were taken today – post the president’s COVID-19 illness – would the answers be different?” he noted.

Dr. Sokol’s work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development but otherwise had no financial conflicts to disclose. Dr. Harrison disclosed that his institution receives grant funding from Merck, Pfizer, and GlaxoSmithKline for pediatric noninfluenza vaccine studies on which he is a subinvestigator, and support from the CDC for pediatric respiratory and gastrointestinal virus surveillance studies on which he is an investigator.

SOURCE: Sokol RL, Grummon AH. Pediatrics. 2020 Sep 30. doi: 10.1542/peds.2020-022871.

Parents who did not vaccinate their children against influenza last year were significantly less likely to do so this year than parents whose children were vaccinated last year, based on survey data from more than 2,000 parents with babies and young children.

Choreograph/Thinkstock

“Pediatric vaccination will be an important component to mitigating a dual influenza/COVID-19 epidemic,” Rebeccah L. Sokol, PhD, of Wayne State University, Detroit, and Anna H. Grummon, PhD, of Harvard School of Public Health, Boston, reported in Pediatrics.

Although the pandemic has increased acceptance of some healthy behaviors including handwashing and social distancing, the impact on influenza vaccination rates remains unknown, they said.

To assess parents’ current intentions for flu vaccination of young children this season, the researchers conducted an online survey of 2,164 parents or guardians of children aged between 6 months and 5 years in the United States. The 15-minute online survey was conducted in May 2020 and participants received gift cards. The primary outcome was the impact of the COVID-19 pandemic on parental intentions for having their child vaccinated against seasonal flu this year.

“We measured change categorically, with response options ranging from 1 (I became much less likely to get my child the flu shot next year) to 5 (I became much more likely to get my child the flu shot next year),” the researchers said.
 

Pandemic changes some parents’ plans

Overall, 60% of parents said that the ongoing pandemic had altered their flu vaccination intentions for their children. About 34% percent of parents whose children did not receive flu vaccine last year said they would not seek the vaccine this year because of the pandemic, compared with 25% of parents whose children received last year’s flu vaccine, a statistically significant difference (P < .001).

Approximately 21% of parents whose children received no flu vaccine last year said the pandemic made them more likely to seek vaccination for the 2020-2021 season, compared with 38% of parents whose children received last year’s flu vaccine.

“These results suggest that overall seasonal influenza vaccination rates may not increase simply because of an ongoing infectious disease pandemic. Instead, a significant predictor of future behavior remains past behavior,” Dr. Sokol and Dr. Grummon said.

The study findings were limited by several factors including the use of a convenience sample and the timing of the survey in May 2020, meaning that survey results might not be generalizable this fall as the pandemic persists, they noted. “Additionally, we assessed intentions to vaccinate; future research will clarify the COVID-19 pandemic’s influence on actual vaccination behaviors.”

The challenge of how to increase uptake of the influenza vaccine during the era of COVID-19 remains, and targeted efforts could include social norms messaging through social media, mass media, or health care providers to increase parents’ intentions to vaccinate, as well as vaccination reminders and presumptive announcements from health care providers that present vaccination as the default option, the researchers added.
 

Potential for ‘twindemic’ is real

The uptake of flu vaccination is especially important this year, Christopher J. Harrison, MD, director of the vaccine and treatment evaluation unit and professor of pediatrics at the University of Missouri–Kansas City, said in an interview.

“This year we are entering a flu season where the certainty of the timing as well as the potential severity of the season are not known. That said, social distancing and wearing masks – to the extent that enough people conform to COVID-19 precautions – could delay or even blunt the usual influenza season,” he noted.

Unfortunately, the Centers for Disease Control and Prevention and the Food and Drug Administration have had their credibility damaged by the challenges of creating a successful response on the fly to a uniquely multifaceted virus to which previous rules do not apply, Dr. Harrison said. In addition, public confidence was eroded when information about testing and reopening policies were released by non-CDC nonscientists and labeled “CDC recommended,” with no opportunity for the scientific community to correct inaccuracies.

“The current study reveals that public trust in influenza vaccine and indirectly in health authorities has been affected by the pandemic,” said Dr. Harrison. “Vaccine hesitancy has increased somewhat even among previous vaccine accepters. One wonders if promises of a quick COVID-19 vaccine increased mistrust of the FDA because of safety concerns, even among the most ardent provaccine population, and whether these concerns are bleeding over into influenza vaccine concerns.

“This only adds to the anxiety that families feel about visiting any medical facility for routine vaccines while the pandemic rages, and we now are in a fall SARS-CoV-2 resurgence,” he added.

Although the current study data are concerning, “there could still be a net gain of pediatric influenza vaccine uptake this season because the 34% less likely to immunize among previously nonimmunizing families would be counterbalanced by 21% of the same group being more likely to immunize their children [theoretical net loss of 13%],” Dr. Harrison explained. “But the pandemic seems to have motivated previously influenza-immunizing families, i.e. while 24% were less likely, 39% are more likely to immunize [theoretical net gain of 15%]. That said, we would still be way short of the number needed to get to herd immunity.”

Dr. Harrison said he found the findings somewhat surprising, but perhaps he should not have. “I had hoped for more acceptance rather than most people staying in their prior vaccine ‘opinion lanes,’ ending up with likely little overall net change in plans to immunize despite increased health awareness caused by a pandemic.”

However, “the U.S. population has been polarized on vaccines and particularly influenza vaccines for more than 50 years, so why would a pandemic make us less polarized, particularly when the pandemic itself has been a polarizing event?” he questioned.

The greatest barriers to flu vaccination for children this year include a lack of motivation among families to visit immunization sites, given the ongoing need for social distancing and masks, Dr. Harrison said.

“Another barrier is the waning public confidence in our medical/scientific national leaders and organizations,” he emphasized. “This makes it crucial that primary care providers step up and be extra strong vaccine advocates, despite the fact that pandemic economics and necessary safety processes have stressed providers and devastated practices. Indeed, in times of medical stress, no one gets more trust from families than their own personal provider.”

Ultimately, avenues for future research include asking diverse groups of families what they feel they need to hear to be more engaged in immunizing children against influenza. But for now, the current study findings identify that “the public is not uniformly responding to the pandemic’s influence on their likelihood of immunizing their children against influenza,” Dr. Harrison said.

“We now know the size of the problem and hopefully governments, public health organizations, pediatric advocates and clinical care givers can find ways to magnify the message that a pandemic year is not a year to avoid seasonal influenza vaccine unless one has a true contraindication,” Dr. Harrison said.

In addition, “one wonders if the poll were taken today – post the president’s COVID-19 illness – would the answers be different?” he noted.

Dr. Sokol’s work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development but otherwise had no financial conflicts to disclose. Dr. Harrison disclosed that his institution receives grant funding from Merck, Pfizer, and GlaxoSmithKline for pediatric noninfluenza vaccine studies on which he is a subinvestigator, and support from the CDC for pediatric respiratory and gastrointestinal virus surveillance studies on which he is an investigator.

SOURCE: Sokol RL, Grummon AH. Pediatrics. 2020 Sep 30. doi: 10.1542/peds.2020-022871.

Cardiac stress testing before hip and knee replacements has dropped steadily since 2006, according to results from a new study that also showed major cardiac complications to be low in the absence of stress testing – even among people with established risk factors.

Routine stress testing before noncardiac surgeries has come under fire in recent decades as an overuse of resources and a burden on patients. Practice guidelines issued in 2007 and 2014 by the American College of Cardiology and the American Heart Association sought to limit the use of preoperative testing to patients with specific cardiovascular risk factors who might have their management changed by the test results.

For their study, published online in JAMA Cardiology, Daniel S. Rubin, MD, of the University of Chicago and colleagues looked at employee-based insurance data, which included Medicare Advantage claims, for more than 800,000 total hip or knee arthroplasties (28% hip and 72% knee replacements) conducted between 2004 and 2017.

While some 10% of the cohort (mean age 62, 58% women) received a stress test in the 2 months before surgery, the investigators found that the frequency of preoperative stress testing dropped annually starting in late 2006, when it peaked at about 14%, to about 7% in 2017. Older age, male sex and a Revised Cardiac Risk Index score of 1 or greater were all associated with a higher likelihood of being tested.

The overall frequency of myocardial infarction or cardiac arrest was 0.24%, occurring in 1,677 of 686,067 patients. While the rate was higher in patients with at least one RCRI condition, this did not differ significantly between those who received a preoperative stress test and those who did not (0.60%; 221 of 36,554 vs. 0.57%; 694 of 122,466 patients.

The 2007 and 2014 ACC/AHA guidelines make clear that patients with zero RCRI conditions – which comprise a history of ischemic heart disease, heart failure, insulin therapy for diabetes, cerebrovascular disease, or chronic kidney disease – should not receive a stress test before an intermediate-risk surgery such as a hip or knee replacement. But in this study, Dr. Rubin and his colleagues found that almost half of patients who had no RCRI risk factors were stress tested anyway. This means, Dr. Rubin said in an interview, that “there’s still room for improvement” in reducing testing.

“I never want to question how a physician chooses to practice, but I have to applaud physicians for reining in the use of this test. We’re using less of this test and yet the incidence of myocardial infarction and cardiac arrest is also going down, which also calls into question whether we’re getting better at choosing the right patients for the test; or the test doesn’t impact outcomes; or overall health of these patients is improving,” he said.

One surprise finding in the study, Dr. Rubin noted, was a higher rate of complications among people without RCRI conditions who were stress tested, compared with those who were not, with a mean complication rate of 0.27%, compared with 0.14% among those who did not receive a test (P < .001). “The RCRI doesn’t capture certain things,” Dr. Rubin said. “And we know that no risk stratification tool is going to capture everything.”

The RCRI, he noted, is based on a clinical history. “If you haven’t been diagnosed yet, it won’t appear as a risk factor, even if you’re clearly at risk. The question then becomes for a physician, do you do the test or not? On a day-to-day basis it’s hard to make that decision because you want what’s best for the individual patient – and it’s hard to generalize from a study of 800,000 people what’s right for that one patient. That said, it doesn’t appear that stress testing improves outcomes and a decrease in testing appears appropriate.”

Dr. Rubin and his colleagues described as a weakness of their study that it did not capture the full scope of preoperative stress testing among Medicare patients, who are older and therefore more likely to be tested.

That the 2007 and 2014 practice guidelines bore on the drop in testing was not demonstrated by Dr. Rubin and colleagues’ study, which saw declines begin even before the guidelines were published. Nonetheless, the results appear to validate the approach advocated in the guidelines, said guideline coauthor Joshua Beckman, MD, of Vanderbilt University, whose recent research has focused on identifying risk factors for MI after noncardiac surgery.

“I hope that the guidelines have helped in changing the culture for the use of preoperative stress testing as a regular thing,” Dr. Beckman said in an interview. “In fact, the guidelines say you shouldn’t do anything before an operation that you wouldn’t do anyway. So these findings are certainly in agreement with what we’re suggesting and support the idea that unless you have something that is unstable or active, stress testing isn’t likely to help.”

Annemarie Thompson, MD, of Duke University in Durham, N.C., another coauthor on the 2014 guidelines, commented in an interview that Dr. Rubin and colleagues’ findings of a doubled rate of complications among people without RCRI conditions who were stress tested, compared with those who were not might mean something “other than just sheer overuse or overordering of tests inappropriately.”

Rather, she said, physicians might be seeing something in the clinic that cannot be captured by a screening tool reliant on existing diagnoses. “Maybe when they’re sitting in front of you in a clinic, they’re so immobile that you’re left wondering. Or maybe they haven’t been seen by a doctor in a long time,” Dr. Thompson said. “So they don’t have diagnoses if they haven’t been followed. I think what [this finding] shows is that clinicians are detecting something. They may not know what it is. But we have to give a little wiggle room to the clinician who is sitting there looking at a patient who looks like they may not make it through surgery.”

Dr. Thompson said it would be helpful, after a big-data study like this one, to go through the clinical histories of those patients – in this study fewer than 100 – who had no RCRI risk factors and yet were stress tested and ended up having complications. “Until then we’re not going to solve the mystery,” she said. “But it’s a very, very interesting study.”

Dr. Rubin is the president of DRDR Mobile Health, a company that creates mobile applications for health care and from which he has not received compensation. One of his coauthors on the study, Dr. Peter Nagele, reported fee income from Roche Diagnostics. Dr. Beckman disclosed personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and other pharmaceutical manufacturers. Dr. Thompson has no disclosures.

SOURCE: Rubin et al. JAMA Cardiol. 2020 Sep 30. doi: 10.1001/jamacardio.2020.4311.

Cardiac stress testing before hip and knee replacements has dropped steadily since 2006, according to results from a new study that also showed major cardiac complications to be low in the absence of stress testing – even among people with established risk factors.

Routine stress testing before noncardiac surgeries has come under fire in recent decades as an overuse of resources and a burden on patients. Practice guidelines issued in 2007 and 2014 by the American College of Cardiology and the American Heart Association sought to limit the use of preoperative testing to patients with specific cardiovascular risk factors who might have their management changed by the test results.

For their study, published online in JAMA Cardiology, Daniel S. Rubin, MD, of the University of Chicago and colleagues looked at employee-based insurance data, which included Medicare Advantage claims, for more than 800,000 total hip or knee arthroplasties (28% hip and 72% knee replacements) conducted between 2004 and 2017.

While some 10% of the cohort (mean age 62, 58% women) received a stress test in the 2 months before surgery, the investigators found that the frequency of preoperative stress testing dropped annually starting in late 2006, when it peaked at about 14%, to about 7% in 2017. Older age, male sex and a Revised Cardiac Risk Index score of 1 or greater were all associated with a higher likelihood of being tested.

The overall frequency of myocardial infarction or cardiac arrest was 0.24%, occurring in 1,677 of 686,067 patients. While the rate was higher in patients with at least one RCRI condition, this did not differ significantly between those who received a preoperative stress test and those who did not (0.60%; 221 of 36,554 vs. 0.57%; 694 of 122,466 patients.

The 2007 and 2014 ACC/AHA guidelines make clear that patients with zero RCRI conditions – which comprise a history of ischemic heart disease, heart failure, insulin therapy for diabetes, cerebrovascular disease, or chronic kidney disease – should not receive a stress test before an intermediate-risk surgery such as a hip or knee replacement. But in this study, Dr. Rubin and his colleagues found that almost half of patients who had no RCRI risk factors were stress tested anyway. This means, Dr. Rubin said in an interview, that “there’s still room for improvement” in reducing testing.

“I never want to question how a physician chooses to practice, but I have to applaud physicians for reining in the use of this test. We’re using less of this test and yet the incidence of myocardial infarction and cardiac arrest is also going down, which also calls into question whether we’re getting better at choosing the right patients for the test; or the test doesn’t impact outcomes; or overall health of these patients is improving,” he said.

One surprise finding in the study, Dr. Rubin noted, was a higher rate of complications among people without RCRI conditions who were stress tested, compared with those who were not, with a mean complication rate of 0.27%, compared with 0.14% among those who did not receive a test (P < .001). “The RCRI doesn’t capture certain things,” Dr. Rubin said. “And we know that no risk stratification tool is going to capture everything.”

The RCRI, he noted, is based on a clinical history. “If you haven’t been diagnosed yet, it won’t appear as a risk factor, even if you’re clearly at risk. The question then becomes for a physician, do you do the test or not? On a day-to-day basis it’s hard to make that decision because you want what’s best for the individual patient – and it’s hard to generalize from a study of 800,000 people what’s right for that one patient. That said, it doesn’t appear that stress testing improves outcomes and a decrease in testing appears appropriate.”

Dr. Rubin and his colleagues described as a weakness of their study that it did not capture the full scope of preoperative stress testing among Medicare patients, who are older and therefore more likely to be tested.

That the 2007 and 2014 practice guidelines bore on the drop in testing was not demonstrated by Dr. Rubin and colleagues’ study, which saw declines begin even before the guidelines were published. Nonetheless, the results appear to validate the approach advocated in the guidelines, said guideline coauthor Joshua Beckman, MD, of Vanderbilt University, whose recent research has focused on identifying risk factors for MI after noncardiac surgery.

“I hope that the guidelines have helped in changing the culture for the use of preoperative stress testing as a regular thing,” Dr. Beckman said in an interview. “In fact, the guidelines say you shouldn’t do anything before an operation that you wouldn’t do anyway. So these findings are certainly in agreement with what we’re suggesting and support the idea that unless you have something that is unstable or active, stress testing isn’t likely to help.”

Annemarie Thompson, MD, of Duke University in Durham, N.C., another coauthor on the 2014 guidelines, commented in an interview that Dr. Rubin and colleagues’ findings of a doubled rate of complications among people without RCRI conditions who were stress tested, compared with those who were not might mean something “other than just sheer overuse or overordering of tests inappropriately.”

Rather, she said, physicians might be seeing something in the clinic that cannot be captured by a screening tool reliant on existing diagnoses. “Maybe when they’re sitting in front of you in a clinic, they’re so immobile that you’re left wondering. Or maybe they haven’t been seen by a doctor in a long time,” Dr. Thompson said. “So they don’t have diagnoses if they haven’t been followed. I think what [this finding] shows is that clinicians are detecting something. They may not know what it is. But we have to give a little wiggle room to the clinician who is sitting there looking at a patient who looks like they may not make it through surgery.”

Dr. Thompson said it would be helpful, after a big-data study like this one, to go through the clinical histories of those patients – in this study fewer than 100 – who had no RCRI risk factors and yet were stress tested and ended up having complications. “Until then we’re not going to solve the mystery,” she said. “But it’s a very, very interesting study.”

Dr. Rubin is the president of DRDR Mobile Health, a company that creates mobile applications for health care and from which he has not received compensation. One of his coauthors on the study, Dr. Peter Nagele, reported fee income from Roche Diagnostics. Dr. Beckman disclosed personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and other pharmaceutical manufacturers. Dr. Thompson has no disclosures.

SOURCE: Rubin et al. JAMA Cardiol. 2020 Sep 30. doi: 10.1001/jamacardio.2020.4311.

Cardiac stress testing before hip and knee replacements has dropped steadily since 2006, according to results from a new study that also showed major cardiac complications to be low in the absence of stress testing – even among people with established risk factors.

Routine stress testing before noncardiac surgeries has come under fire in recent decades as an overuse of resources and a burden on patients. Practice guidelines issued in 2007 and 2014 by the American College of Cardiology and the American Heart Association sought to limit the use of preoperative testing to patients with specific cardiovascular risk factors who might have their management changed by the test results.

For their study, published online in JAMA Cardiology, Daniel S. Rubin, MD, of the University of Chicago and colleagues looked at employee-based insurance data, which included Medicare Advantage claims, for more than 800,000 total hip or knee arthroplasties (28% hip and 72% knee replacements) conducted between 2004 and 2017.

While some 10% of the cohort (mean age 62, 58% women) received a stress test in the 2 months before surgery, the investigators found that the frequency of preoperative stress testing dropped annually starting in late 2006, when it peaked at about 14%, to about 7% in 2017. Older age, male sex and a Revised Cardiac Risk Index score of 1 or greater were all associated with a higher likelihood of being tested.

The overall frequency of myocardial infarction or cardiac arrest was 0.24%, occurring in 1,677 of 686,067 patients. While the rate was higher in patients with at least one RCRI condition, this did not differ significantly between those who received a preoperative stress test and those who did not (0.60%; 221 of 36,554 vs. 0.57%; 694 of 122,466 patients.

The 2007 and 2014 ACC/AHA guidelines make clear that patients with zero RCRI conditions – which comprise a history of ischemic heart disease, heart failure, insulin therapy for diabetes, cerebrovascular disease, or chronic kidney disease – should not receive a stress test before an intermediate-risk surgery such as a hip or knee replacement. But in this study, Dr. Rubin and his colleagues found that almost half of patients who had no RCRI risk factors were stress tested anyway. This means, Dr. Rubin said in an interview, that “there’s still room for improvement” in reducing testing.

“I never want to question how a physician chooses to practice, but I have to applaud physicians for reining in the use of this test. We’re using less of this test and yet the incidence of myocardial infarction and cardiac arrest is also going down, which also calls into question whether we’re getting better at choosing the right patients for the test; or the test doesn’t impact outcomes; or overall health of these patients is improving,” he said.

One surprise finding in the study, Dr. Rubin noted, was a higher rate of complications among people without RCRI conditions who were stress tested, compared with those who were not, with a mean complication rate of 0.27%, compared with 0.14% among those who did not receive a test (P < .001). “The RCRI doesn’t capture certain things,” Dr. Rubin said. “And we know that no risk stratification tool is going to capture everything.”

The RCRI, he noted, is based on a clinical history. “If you haven’t been diagnosed yet, it won’t appear as a risk factor, even if you’re clearly at risk. The question then becomes for a physician, do you do the test or not? On a day-to-day basis it’s hard to make that decision because you want what’s best for the individual patient – and it’s hard to generalize from a study of 800,000 people what’s right for that one patient. That said, it doesn’t appear that stress testing improves outcomes and a decrease in testing appears appropriate.”

Dr. Rubin and his colleagues described as a weakness of their study that it did not capture the full scope of preoperative stress testing among Medicare patients, who are older and therefore more likely to be tested.

That the 2007 and 2014 practice guidelines bore on the drop in testing was not demonstrated by Dr. Rubin and colleagues’ study, which saw declines begin even before the guidelines were published. Nonetheless, the results appear to validate the approach advocated in the guidelines, said guideline coauthor Joshua Beckman, MD, of Vanderbilt University, whose recent research has focused on identifying risk factors for MI after noncardiac surgery.

“I hope that the guidelines have helped in changing the culture for the use of preoperative stress testing as a regular thing,” Dr. Beckman said in an interview. “In fact, the guidelines say you shouldn’t do anything before an operation that you wouldn’t do anyway. So these findings are certainly in agreement with what we’re suggesting and support the idea that unless you have something that is unstable or active, stress testing isn’t likely to help.”

Annemarie Thompson, MD, of Duke University in Durham, N.C., another coauthor on the 2014 guidelines, commented in an interview that Dr. Rubin and colleagues’ findings of a doubled rate of complications among people without RCRI conditions who were stress tested, compared with those who were not might mean something “other than just sheer overuse or overordering of tests inappropriately.”

Rather, she said, physicians might be seeing something in the clinic that cannot be captured by a screening tool reliant on existing diagnoses. “Maybe when they’re sitting in front of you in a clinic, they’re so immobile that you’re left wondering. Or maybe they haven’t been seen by a doctor in a long time,” Dr. Thompson said. “So they don’t have diagnoses if they haven’t been followed. I think what [this finding] shows is that clinicians are detecting something. They may not know what it is. But we have to give a little wiggle room to the clinician who is sitting there looking at a patient who looks like they may not make it through surgery.”

Dr. Thompson said it would be helpful, after a big-data study like this one, to go through the clinical histories of those patients – in this study fewer than 100 – who had no RCRI risk factors and yet were stress tested and ended up having complications. “Until then we’re not going to solve the mystery,” she said. “But it’s a very, very interesting study.”

Dr. Rubin is the president of DRDR Mobile Health, a company that creates mobile applications for health care and from which he has not received compensation. One of his coauthors on the study, Dr. Peter Nagele, reported fee income from Roche Diagnostics. Dr. Beckman disclosed personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and other pharmaceutical manufacturers. Dr. Thompson has no disclosures.

SOURCE: Rubin et al. JAMA Cardiol. 2020 Sep 30. doi: 10.1001/jamacardio.2020.4311.

Music listening and singing each showed early, promising evidence for producing cardiovascular benefits, part of a burgeoning area of research that is exploring and documenting ways to effectively use music to improve health.

A study run at four centers in Italy randomized 159 patients with heart failure, primarily New York Heart Association class I or II disease, to either a daily regimen of at least 30 minutes spent listening to music daily or to a control group that received usual care with no music prescription. After 3 months, the 82 patients in the daily music-listening group had a statistically significant improvement in their Minnesota Living with Heart Failure Questionnaire scores, compared with 77 controls for the study’s primary outcome measure. The results also showed significant benefits, compared with placebo, for other, secondary efficacy measures including improvements in anxiety, depression, sleep quality, and cognition.

Although the results are considered preliminary, they drew significant attention when published in July 2020 (J Card Fail. 2020 Jul 1;26[7]:541-9), where it was accompanied by two editorials in the same issue as well as an editor’s statement. All these commentators as well as other experts interested in music as medicine gathered to further discuss the topic during a panel session at the virtual annual meeting of the Heart Failure Society of America.

Music as a calming influence

The source of the primary benefits seen in this Italian study likely involved “emotional, psychological, and relaxation,” suggested Jerome L. Fleg, MD, program officer for clinical cardiovascular disease at the National Heart, Lung, and Blood Institute in Bethesda, Md. Researchers had used calming potential as a major criterion when selecting the 80 classical pieces that the heart failure patients in the intervention arm of the study could shuffle on their play lists.

“The tempo/rhythm was set up in a range between 60 and 80 beats per minute, because this range mirrors the human heart rate and facilitates relaxation,” the investigators said in their published report. Unfortunately, noted Dr. Fleg, the study lacked physiologic and biomarker measurements that could have provided objective evidence of effects from music. And the study failed to include a control arm of patients instructed to spend 30 minutes a day resting and relaxing without instruction to listen to music, he noted.

Dr. Fleg had authored one of the July editorials, where he said “It is hoped that findings from these studies and others can expand the scientific evidence for music-based interventions and bring these therapies into clinical practice. The current study from Burrai et al. is a positive step in this direction for patients with heart failure.” (J Card Fail. 2020 Jul 1;26[7]: 550-1). What’s needed now, he added during the virtual session, are “more objective data” to better and more comprehensively document the benefits from a music-based intervention in patients with heart failure.
 

An add-on to standard care

The findings in heart failure patients follows a growing literature that’s shown music can generate a restful state by doing things like activating autonomic parasympathetic outflow while dampening sympathetic outflow. This produces moderation in mood and emotion as well as depressed heart rate, lowered blood pressure, and slowed respiration, commented Emmeline Edwards, PhD director of the division of extramural research of the National Center for Complementary and Integrative Health in Bethesda, Md. Music also seems able to stimulate higher-order brain regions that can result in reduced psychological stress, anxiety, and depression.

“It’s a promising protective intervention to add to standard care for cardiac patients,” Dr. Edwards said during the virtual session. “Music is part of the toolbox for managing symptoms and improving health and well-being.”

“Music is not a substitute for standard therapy, but could add to it,” declared Dr. Fleg.

The already-established intervention known as music therapy has identified music’s ability to modulate breathing as an important mediator of music’s effect.

“Breathing is one of the few physiological processes that can be voluntarily controlled making it a viable target for intervention,” noted opera soprano Renée Fleming and Sheri L. Robb, PhD, in the second editorial that accompanied the Italian heart failure report (J Card Fail. 2020 Jul 1;26[7]:552-4). The music-listening intervention “may have had more effect if they had used compositional features [of the music] to teach patients how to structure their breathing,” said Dr. Robb, a music therapist at Indiana University–Purdue University Indianapolis, during the virtual session.

Another variable to consider is the type of music. “What is the emotional response to the music, and how does that affect heart rate,” wondered Dr. Robb, a professor at the Indiana University School of Nursing in Indianapolis.

Music as exercise

The division that Dr. Edwards directs recently funded a pilot study that assessed the feasibility of using music to stimulate activity and improve breathing another way, by repurposing singing as a novel form of rehabilitative exercise.

The pilot study enrolled patients with coronary disease into a randomized study that tested whether a 14-minute session of supervised singing could produce acute improvement in vascular function, “a biomarker for the risk of future cardiovascular disease events,” explained Jacqueline P. Kulinski, MD, a preventive cardiologist at the Medical College of Wisconsin in Milwaukee. Dr. Kulinski did not report details of her yet-unpublished study, but said that her initial findings held promise for developing musical activities such as singing as a novel way to stimulate therapeutic physical activity in patients with heart disease.

“It’s exciting to see this signal” of benefit. “I envision music therapy as a part of cardiac rehabilitation, or an alternative for patients who can’t participate in traditional rehab,” Dr. Kulinski said during the virtual session. “I think of singing as a physical activity, as exercise, and using this exercise as medicine.”

Harmonizing with the NIH

“Singing is like swimming: You need to hold your breath,” agreed Ms. Fleming, who participated on the virtual panel and has spearheaded a collaboration between the National Institutes of Health and the Kennedy Center for the Performing Arts, the Sound Health Initiative, that’s coordinating research into the connections between music and health. Ms. Fleming helped launch the Sound Health Initiative in 2017 by coauthoring a JAMA article with the NIH director that spelled out the rationale and goals of the project (JAMA. 2017 Jun 27;317[24]:2470-1), and by launching a lecture tour on the topic in a presentation she calls Music and the Mind.

Andrew Eccles

Ms. Fleming has given her talk in more than 30 locations worldwide, and she’s found that “audiences love” the combination of neuroscience and music that her talks cover, she said. Her lectures highlight that, in addition to cardiovascular disease, the potential for music therapy and related interventions has been shown in patients with disorders that include autism, psychosis, pain, Parkinson’s disease, Alzheimer’s disease, and epilepsy.

The research highlighted in the session “opens new doors to prevention and treatment strategies using music for patients with heart failure and cardiovascular disease,” summed up Biykem Bozkurt, MD, professor of medicine at the Baylor College of Medicine in Houston and president of the Heart Failure Society of America, who helped organize the virtual session.

Dr. Fleg, Dr. Edwards, Dr. Robb, Dr Kulinski, Ms. Fleming, and Dr. Bozkurt had no relevant financial disclosures.
 

[email protected]
 

Music listening and singing each showed early, promising evidence for producing cardiovascular benefits, part of a burgeoning area of research that is exploring and documenting ways to effectively use music to improve health.

A study run at four centers in Italy randomized 159 patients with heart failure, primarily New York Heart Association class I or II disease, to either a daily regimen of at least 30 minutes spent listening to music daily or to a control group that received usual care with no music prescription. After 3 months, the 82 patients in the daily music-listening group had a statistically significant improvement in their Minnesota Living with Heart Failure Questionnaire scores, compared with 77 controls for the study’s primary outcome measure. The results also showed significant benefits, compared with placebo, for other, secondary efficacy measures including improvements in anxiety, depression, sleep quality, and cognition.

Although the results are considered preliminary, they drew significant attention when published in July 2020 (J Card Fail. 2020 Jul 1;26[7]:541-9), where it was accompanied by two editorials in the same issue as well as an editor’s statement. All these commentators as well as other experts interested in music as medicine gathered to further discuss the topic during a panel session at the virtual annual meeting of the Heart Failure Society of America.

Music as a calming influence

The source of the primary benefits seen in this Italian study likely involved “emotional, psychological, and relaxation,” suggested Jerome L. Fleg, MD, program officer for clinical cardiovascular disease at the National Heart, Lung, and Blood Institute in Bethesda, Md. Researchers had used calming potential as a major criterion when selecting the 80 classical pieces that the heart failure patients in the intervention arm of the study could shuffle on their play lists.

“The tempo/rhythm was set up in a range between 60 and 80 beats per minute, because this range mirrors the human heart rate and facilitates relaxation,” the investigators said in their published report. Unfortunately, noted Dr. Fleg, the study lacked physiologic and biomarker measurements that could have provided objective evidence of effects from music. And the study failed to include a control arm of patients instructed to spend 30 minutes a day resting and relaxing without instruction to listen to music, he noted.

Dr. Fleg had authored one of the July editorials, where he said “It is hoped that findings from these studies and others can expand the scientific evidence for music-based interventions and bring these therapies into clinical practice. The current study from Burrai et al. is a positive step in this direction for patients with heart failure.” (J Card Fail. 2020 Jul 1;26[7]: 550-1). What’s needed now, he added during the virtual session, are “more objective data” to better and more comprehensively document the benefits from a music-based intervention in patients with heart failure.
 

An add-on to standard care

The findings in heart failure patients follows a growing literature that’s shown music can generate a restful state by doing things like activating autonomic parasympathetic outflow while dampening sympathetic outflow. This produces moderation in mood and emotion as well as depressed heart rate, lowered blood pressure, and slowed respiration, commented Emmeline Edwards, PhD director of the division of extramural research of the National Center for Complementary and Integrative Health in Bethesda, Md. Music also seems able to stimulate higher-order brain regions that can result in reduced psychological stress, anxiety, and depression.

“It’s a promising protective intervention to add to standard care for cardiac patients,” Dr. Edwards said during the virtual session. “Music is part of the toolbox for managing symptoms and improving health and well-being.”

“Music is not a substitute for standard therapy, but could add to it,” declared Dr. Fleg.

The already-established intervention known as music therapy has identified music’s ability to modulate breathing as an important mediator of music’s effect.

“Breathing is one of the few physiological processes that can be voluntarily controlled making it a viable target for intervention,” noted opera soprano Renée Fleming and Sheri L. Robb, PhD, in the second editorial that accompanied the Italian heart failure report (J Card Fail. 2020 Jul 1;26[7]:552-4). The music-listening intervention “may have had more effect if they had used compositional features [of the music] to teach patients how to structure their breathing,” said Dr. Robb, a music therapist at Indiana University–Purdue University Indianapolis, during the virtual session.

Another variable to consider is the type of music. “What is the emotional response to the music, and how does that affect heart rate,” wondered Dr. Robb, a professor at the Indiana University School of Nursing in Indianapolis.

Music as exercise

The division that Dr. Edwards directs recently funded a pilot study that assessed the feasibility of using music to stimulate activity and improve breathing another way, by repurposing singing as a novel form of rehabilitative exercise.

The pilot study enrolled patients with coronary disease into a randomized study that tested whether a 14-minute session of supervised singing could produce acute improvement in vascular function, “a biomarker for the risk of future cardiovascular disease events,” explained Jacqueline P. Kulinski, MD, a preventive cardiologist at the Medical College of Wisconsin in Milwaukee. Dr. Kulinski did not report details of her yet-unpublished study, but said that her initial findings held promise for developing musical activities such as singing as a novel way to stimulate therapeutic physical activity in patients with heart disease.

“It’s exciting to see this signal” of benefit. “I envision music therapy as a part of cardiac rehabilitation, or an alternative for patients who can’t participate in traditional rehab,” Dr. Kulinski said during the virtual session. “I think of singing as a physical activity, as exercise, and using this exercise as medicine.”

Harmonizing with the NIH

“Singing is like swimming: You need to hold your breath,” agreed Ms. Fleming, who participated on the virtual panel and has spearheaded a collaboration between the National Institutes of Health and the Kennedy Center for the Performing Arts, the Sound Health Initiative, that’s coordinating research into the connections between music and health. Ms. Fleming helped launch the Sound Health Initiative in 2017 by coauthoring a JAMA article with the NIH director that spelled out the rationale and goals of the project (JAMA. 2017 Jun 27;317[24]:2470-1), and by launching a lecture tour on the topic in a presentation she calls Music and the Mind.

Andrew Eccles

Ms. Fleming has given her talk in more than 30 locations worldwide, and she’s found that “audiences love” the combination of neuroscience and music that her talks cover, she said. Her lectures highlight that, in addition to cardiovascular disease, the potential for music therapy and related interventions has been shown in patients with disorders that include autism, psychosis, pain, Parkinson’s disease, Alzheimer’s disease, and epilepsy.

The research highlighted in the session “opens new doors to prevention and treatment strategies using music for patients with heart failure and cardiovascular disease,” summed up Biykem Bozkurt, MD, professor of medicine at the Baylor College of Medicine in Houston and president of the Heart Failure Society of America, who helped organize the virtual session.

Dr. Fleg, Dr. Edwards, Dr. Robb, Dr Kulinski, Ms. Fleming, and Dr. Bozkurt had no relevant financial disclosures.
 

[email protected]
 

Music listening and singing each showed early, promising evidence for producing cardiovascular benefits, part of a burgeoning area of research that is exploring and documenting ways to effectively use music to improve health.

A study run at four centers in Italy randomized 159 patients with heart failure, primarily New York Heart Association class I or II disease, to either a daily regimen of at least 30 minutes spent listening to music daily or to a control group that received usual care with no music prescription. After 3 months, the 82 patients in the daily music-listening group had a statistically significant improvement in their Minnesota Living with Heart Failure Questionnaire scores, compared with 77 controls for the study’s primary outcome measure. The results also showed significant benefits, compared with placebo, for other, secondary efficacy measures including improvements in anxiety, depression, sleep quality, and cognition.

Although the results are considered preliminary, they drew significant attention when published in July 2020 (J Card Fail. 2020 Jul 1;26[7]:541-9), where it was accompanied by two editorials in the same issue as well as an editor’s statement. All these commentators as well as other experts interested in music as medicine gathered to further discuss the topic during a panel session at the virtual annual meeting of the Heart Failure Society of America.

Music as a calming influence

The source of the primary benefits seen in this Italian study likely involved “emotional, psychological, and relaxation,” suggested Jerome L. Fleg, MD, program officer for clinical cardiovascular disease at the National Heart, Lung, and Blood Institute in Bethesda, Md. Researchers had used calming potential as a major criterion when selecting the 80 classical pieces that the heart failure patients in the intervention arm of the study could shuffle on their play lists.

“The tempo/rhythm was set up in a range between 60 and 80 beats per minute, because this range mirrors the human heart rate and facilitates relaxation,” the investigators said in their published report. Unfortunately, noted Dr. Fleg, the study lacked physiologic and biomarker measurements that could have provided objective evidence of effects from music. And the study failed to include a control arm of patients instructed to spend 30 minutes a day resting and relaxing without instruction to listen to music, he noted.

Dr. Fleg had authored one of the July editorials, where he said “It is hoped that findings from these studies and others can expand the scientific evidence for music-based interventions and bring these therapies into clinical practice. The current study from Burrai et al. is a positive step in this direction for patients with heart failure.” (J Card Fail. 2020 Jul 1;26[7]: 550-1). What’s needed now, he added during the virtual session, are “more objective data” to better and more comprehensively document the benefits from a music-based intervention in patients with heart failure.
 

An add-on to standard care

The findings in heart failure patients follows a growing literature that’s shown music can generate a restful state by doing things like activating autonomic parasympathetic outflow while dampening sympathetic outflow. This produces moderation in mood and emotion as well as depressed heart rate, lowered blood pressure, and slowed respiration, commented Emmeline Edwards, PhD director of the division of extramural research of the National Center for Complementary and Integrative Health in Bethesda, Md. Music also seems able to stimulate higher-order brain regions that can result in reduced psychological stress, anxiety, and depression.

“It’s a promising protective intervention to add to standard care for cardiac patients,” Dr. Edwards said during the virtual session. “Music is part of the toolbox for managing symptoms and improving health and well-being.”

“Music is not a substitute for standard therapy, but could add to it,” declared Dr. Fleg.

The already-established intervention known as music therapy has identified music’s ability to modulate breathing as an important mediator of music’s effect.

“Breathing is one of the few physiological processes that can be voluntarily controlled making it a viable target for intervention,” noted opera soprano Renée Fleming and Sheri L. Robb, PhD, in the second editorial that accompanied the Italian heart failure report (J Card Fail. 2020 Jul 1;26[7]:552-4). The music-listening intervention “may have had more effect if they had used compositional features [of the music] to teach patients how to structure their breathing,” said Dr. Robb, a music therapist at Indiana University–Purdue University Indianapolis, during the virtual session.

Another variable to consider is the type of music. “What is the emotional response to the music, and how does that affect heart rate,” wondered Dr. Robb, a professor at the Indiana University School of Nursing in Indianapolis.

Music as exercise

The division that Dr. Edwards directs recently funded a pilot study that assessed the feasibility of using music to stimulate activity and improve breathing another way, by repurposing singing as a novel form of rehabilitative exercise.

The pilot study enrolled patients with coronary disease into a randomized study that tested whether a 14-minute session of supervised singing could produce acute improvement in vascular function, “a biomarker for the risk of future cardiovascular disease events,” explained Jacqueline P. Kulinski, MD, a preventive cardiologist at the Medical College of Wisconsin in Milwaukee. Dr. Kulinski did not report details of her yet-unpublished study, but said that her initial findings held promise for developing musical activities such as singing as a novel way to stimulate therapeutic physical activity in patients with heart disease.

“It’s exciting to see this signal” of benefit. “I envision music therapy as a part of cardiac rehabilitation, or an alternative for patients who can’t participate in traditional rehab,” Dr. Kulinski said during the virtual session. “I think of singing as a physical activity, as exercise, and using this exercise as medicine.”

Harmonizing with the NIH

“Singing is like swimming: You need to hold your breath,” agreed Ms. Fleming, who participated on the virtual panel and has spearheaded a collaboration between the National Institutes of Health and the Kennedy Center for the Performing Arts, the Sound Health Initiative, that’s coordinating research into the connections between music and health. Ms. Fleming helped launch the Sound Health Initiative in 2017 by coauthoring a JAMA article with the NIH director that spelled out the rationale and goals of the project (JAMA. 2017 Jun 27;317[24]:2470-1), and by launching a lecture tour on the topic in a presentation she calls Music and the Mind.

Andrew Eccles

Ms. Fleming has given her talk in more than 30 locations worldwide, and she’s found that “audiences love” the combination of neuroscience and music that her talks cover, she said. Her lectures highlight that, in addition to cardiovascular disease, the potential for music therapy and related interventions has been shown in patients with disorders that include autism, psychosis, pain, Parkinson’s disease, Alzheimer’s disease, and epilepsy.

The research highlighted in the session “opens new doors to prevention and treatment strategies using music for patients with heart failure and cardiovascular disease,” summed up Biykem Bozkurt, MD, professor of medicine at the Baylor College of Medicine in Houston and president of the Heart Failure Society of America, who helped organize the virtual session.

Dr. Fleg, Dr. Edwards, Dr. Robb, Dr Kulinski, Ms. Fleming, and Dr. Bozkurt had no relevant financial disclosures.
 

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