Guidelines

An American Gastroenterological Association practice update on deprescribing proton-pump inhibitors (PPIs) delineates conditions under which drug withdrawal should be considered, and acknowledges that conversations between physicians and patients can be complicated. An inappropriate decision to discontinue PPI therapy can have significant consequences for the patient, while continued inappropriate use raises health care costs and may rarely lead to adverse effects.

One purpose of the update is to provide guidance when patients and providers don’t have the resources to systematically examine the issue, especially when other medical concerns may be in play. The authors also suggested that physicians include pharmacists in the employment of the best practices advice.

monkeybusinessimages/Thinkstock

“None of these statements represents a radical departure from previously published guidance on PPI appropriateness and deprescribing: Our [recommendations] simply seek to summarize the evidence and to provide the clinician with a single document which distills the evidence down into clinically applicable guidance statements,” Laura Targownik, MD, associate professor of medicine at the University of Toronto and corresponding author of the practice update published in Gastroenterology said in an interview.

“PPIs are highly effective medications for specific gastrointestinal conditions, and are largely safe. However, PPIs are often used in situations where they have minimal and no proven benefit, leading to unnecessary health care spending and unnecessary exposure to drugs. Our paper helps clinicians identify which patients require long-term PPI use as well as those who may be using them unnecessarily, and provides actionable advice on how to deprescribe PPIs from those deemed to be using them without clear benefit,” said Dr. Targownik.

An estimated 7%-15% of health care patients in general and 40% of those over 70 use PPIs at any given time, making them among the most commonly used drugs. About one in four patients who start PPIs will use them for a year or more. Aside from their use for acid-mediated upper gastrointestinal conditions, PPIs often find use for less well-defined complaints. Since PPIs are available over the counter, physicians may not even be involved in a patient’s decision to use them.

Although PPI use has been associated with adverse events, including chronic kidney disease, fractures, dementia, and greater risk of COVID-19 infection, there is not high-quality evidence to suggest that PPIs are directly responsible for any of these adverse events.

The authors suggested the primary care provider should periodically review and document the complaints or indications that prompt PPI use. When a patient is found to have no chronic condition that PPIs could reasonably address, the physician should consider a trial withdrawal. Patients who take PPIs twice daily for a known chronic condition should be considered for a reduction to a once-daily dose.

In general, PPI discontinuation is not a good option for most patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture. The same is true for patients with Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis.

Before any deprescribing is considered, the patient should be evaluated for risk of upper gastrointestinal bleeding, and those at high risk are not candidates for PPI deprescribing.

When the decision is made to withdraw PPIs, the patient should be advised of an increased risk of transient upper gastrointestinal symptoms caused by rebound acid hypersecretion.

The withdrawal of PPIs can be done abruptly, or the dose can be tapered gradually.

PPI-associated adverse events should not be a consideration when discussing the option of withdrawing from PPIs. Instead, the decision should be based on the absence of a specific reason for their use. A history of such adverse events, or a current adverse event, should not be a sole reason for discontinuation, nor should risk factors associated with risk of adverse events. Concerns about adverse events have driven recent interest in reducing use of PPIs, but those adverse events were identified through retrospective studies and may be only associated with PPI use rather than caused by it. In many cases there is no plausible mechanistic cause, and no clinical trials have demonstrated increased adverse events in PPI users.

Three-quarters of physicians say they have altered treatment plans for patients because of concerns about PPI adverse events, and 80% say they would advise patients to withdraw PPIs if they learned the patient was at increased risk of upper gastrointestinal bleeding. Unnecessary withdrawal can lead to recurrent symptoms and complications when PPIs are effective treatments. “Therefore, physicians should not use concern about unproven complications of PPI use as a justification for PPI deprescribing if there remain ongoing valid indications for PPI use,” the authors wrote.

Dr. Targownik has received investigator-initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Roche Canada, and Sandoz Canada. She is the lead on an IBD registry supported by AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Amgen Canada, Roche Canada, and Sandoz Canada. None of the companies with whom Dr. Targownik has a relation are involved in the manufacturing, distribution, or sales of PPIs or any other agents mentioned in the manuscript.

An American Gastroenterological Association practice update on deprescribing proton-pump inhibitors (PPIs) delineates conditions under which drug withdrawal should be considered, and acknowledges that conversations between physicians and patients can be complicated. An inappropriate decision to discontinue PPI therapy can have significant consequences for the patient, while continued inappropriate use raises health care costs and may rarely lead to adverse effects.

One purpose of the update is to provide guidance when patients and providers don’t have the resources to systematically examine the issue, especially when other medical concerns may be in play. The authors also suggested that physicians include pharmacists in the employment of the best practices advice.

monkeybusinessimages/Thinkstock

“None of these statements represents a radical departure from previously published guidance on PPI appropriateness and deprescribing: Our [recommendations] simply seek to summarize the evidence and to provide the clinician with a single document which distills the evidence down into clinically applicable guidance statements,” Laura Targownik, MD, associate professor of medicine at the University of Toronto and corresponding author of the practice update published in Gastroenterology said in an interview.

“PPIs are highly effective medications for specific gastrointestinal conditions, and are largely safe. However, PPIs are often used in situations where they have minimal and no proven benefit, leading to unnecessary health care spending and unnecessary exposure to drugs. Our paper helps clinicians identify which patients require long-term PPI use as well as those who may be using them unnecessarily, and provides actionable advice on how to deprescribe PPIs from those deemed to be using them without clear benefit,” said Dr. Targownik.

An estimated 7%-15% of health care patients in general and 40% of those over 70 use PPIs at any given time, making them among the most commonly used drugs. About one in four patients who start PPIs will use them for a year or more. Aside from their use for acid-mediated upper gastrointestinal conditions, PPIs often find use for less well-defined complaints. Since PPIs are available over the counter, physicians may not even be involved in a patient’s decision to use them.

Although PPI use has been associated with adverse events, including chronic kidney disease, fractures, dementia, and greater risk of COVID-19 infection, there is not high-quality evidence to suggest that PPIs are directly responsible for any of these adverse events.

The authors suggested the primary care provider should periodically review and document the complaints or indications that prompt PPI use. When a patient is found to have no chronic condition that PPIs could reasonably address, the physician should consider a trial withdrawal. Patients who take PPIs twice daily for a known chronic condition should be considered for a reduction to a once-daily dose.

In general, PPI discontinuation is not a good option for most patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture. The same is true for patients with Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis.

Before any deprescribing is considered, the patient should be evaluated for risk of upper gastrointestinal bleeding, and those at high risk are not candidates for PPI deprescribing.

When the decision is made to withdraw PPIs, the patient should be advised of an increased risk of transient upper gastrointestinal symptoms caused by rebound acid hypersecretion.

The withdrawal of PPIs can be done abruptly, or the dose can be tapered gradually.

PPI-associated adverse events should not be a consideration when discussing the option of withdrawing from PPIs. Instead, the decision should be based on the absence of a specific reason for their use. A history of such adverse events, or a current adverse event, should not be a sole reason for discontinuation, nor should risk factors associated with risk of adverse events. Concerns about adverse events have driven recent interest in reducing use of PPIs, but those adverse events were identified through retrospective studies and may be only associated with PPI use rather than caused by it. In many cases there is no plausible mechanistic cause, and no clinical trials have demonstrated increased adverse events in PPI users.

Three-quarters of physicians say they have altered treatment plans for patients because of concerns about PPI adverse events, and 80% say they would advise patients to withdraw PPIs if they learned the patient was at increased risk of upper gastrointestinal bleeding. Unnecessary withdrawal can lead to recurrent symptoms and complications when PPIs are effective treatments. “Therefore, physicians should not use concern about unproven complications of PPI use as a justification for PPI deprescribing if there remain ongoing valid indications for PPI use,” the authors wrote.

Dr. Targownik has received investigator-initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Roche Canada, and Sandoz Canada. She is the lead on an IBD registry supported by AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Amgen Canada, Roche Canada, and Sandoz Canada. None of the companies with whom Dr. Targownik has a relation are involved in the manufacturing, distribution, or sales of PPIs or any other agents mentioned in the manuscript.

An American Gastroenterological Association practice update on deprescribing proton-pump inhibitors (PPIs) delineates conditions under which drug withdrawal should be considered, and acknowledges that conversations between physicians and patients can be complicated. An inappropriate decision to discontinue PPI therapy can have significant consequences for the patient, while continued inappropriate use raises health care costs and may rarely lead to adverse effects.

One purpose of the update is to provide guidance when patients and providers don’t have the resources to systematically examine the issue, especially when other medical concerns may be in play. The authors also suggested that physicians include pharmacists in the employment of the best practices advice.

monkeybusinessimages/Thinkstock

“None of these statements represents a radical departure from previously published guidance on PPI appropriateness and deprescribing: Our [recommendations] simply seek to summarize the evidence and to provide the clinician with a single document which distills the evidence down into clinically applicable guidance statements,” Laura Targownik, MD, associate professor of medicine at the University of Toronto and corresponding author of the practice update published in Gastroenterology said in an interview.

“PPIs are highly effective medications for specific gastrointestinal conditions, and are largely safe. However, PPIs are often used in situations where they have minimal and no proven benefit, leading to unnecessary health care spending and unnecessary exposure to drugs. Our paper helps clinicians identify which patients require long-term PPI use as well as those who may be using them unnecessarily, and provides actionable advice on how to deprescribe PPIs from those deemed to be using them without clear benefit,” said Dr. Targownik.

An estimated 7%-15% of health care patients in general and 40% of those over 70 use PPIs at any given time, making them among the most commonly used drugs. About one in four patients who start PPIs will use them for a year or more. Aside from their use for acid-mediated upper gastrointestinal conditions, PPIs often find use for less well-defined complaints. Since PPIs are available over the counter, physicians may not even be involved in a patient’s decision to use them.

Although PPI use has been associated with adverse events, including chronic kidney disease, fractures, dementia, and greater risk of COVID-19 infection, there is not high-quality evidence to suggest that PPIs are directly responsible for any of these adverse events.

The authors suggested the primary care provider should periodically review and document the complaints or indications that prompt PPI use. When a patient is found to have no chronic condition that PPIs could reasonably address, the physician should consider a trial withdrawal. Patients who take PPIs twice daily for a known chronic condition should be considered for a reduction to a once-daily dose.

In general, PPI discontinuation is not a good option for most patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture. The same is true for patients with Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis.

Before any deprescribing is considered, the patient should be evaluated for risk of upper gastrointestinal bleeding, and those at high risk are not candidates for PPI deprescribing.

When the decision is made to withdraw PPIs, the patient should be advised of an increased risk of transient upper gastrointestinal symptoms caused by rebound acid hypersecretion.

The withdrawal of PPIs can be done abruptly, or the dose can be tapered gradually.

PPI-associated adverse events should not be a consideration when discussing the option of withdrawing from PPIs. Instead, the decision should be based on the absence of a specific reason for their use. A history of such adverse events, or a current adverse event, should not be a sole reason for discontinuation, nor should risk factors associated with risk of adverse events. Concerns about adverse events have driven recent interest in reducing use of PPIs, but those adverse events were identified through retrospective studies and may be only associated with PPI use rather than caused by it. In many cases there is no plausible mechanistic cause, and no clinical trials have demonstrated increased adverse events in PPI users.

Three-quarters of physicians say they have altered treatment plans for patients because of concerns about PPI adverse events, and 80% say they would advise patients to withdraw PPIs if they learned the patient was at increased risk of upper gastrointestinal bleeding. Unnecessary withdrawal can lead to recurrent symptoms and complications when PPIs are effective treatments. “Therefore, physicians should not use concern about unproven complications of PPI use as a justification for PPI deprescribing if there remain ongoing valid indications for PPI use,” the authors wrote.

Dr. Targownik has received investigator-initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Roche Canada, and Sandoz Canada. She is the lead on an IBD registry supported by AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Amgen Canada, Roche Canada, and Sandoz Canada. None of the companies with whom Dr. Targownik has a relation are involved in the manufacturing, distribution, or sales of PPIs or any other agents mentioned in the manuscript.

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

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

Catherine Hackett/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Catherine Hackett/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Catherine Hackett/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

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

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

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

Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.

The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.

The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).

The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.

It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.

“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”

The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.

Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”

He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.

“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”

Rehospitalizations and valve thrombosis

The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.

They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.

“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”

Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”

The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.

“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
 

MIs, bleeding, and LBBB

The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.

“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.

The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.

With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.

The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.

Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.

Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”

Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.

Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.

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

The American College of Cardiology has issued a new health policy statement directed at eliminating the bias, discrimination, bullying, and harassment that hamstrings the delivery of quality cardiovascular care.

“We pay a lot of attention, of course, to our patients and patient care issues but our ability to care optimally for patients is limited if the workforce is handicapped in any way,” said Pamela S. Douglas, MD, of Duke University, Durham, N.C., who cochaired the writing committee.

The document is the second in the ACC’s diversity inclusion initiative, following the 2019 report on equal compensation and opportunity in cardiology, but the foundation for the work actually started 5 years ago, she told this news organization.

“Unfortunately, COVID and other world events have created a climate in the United States where people don’t treat each other terribly well,” Dr. Douglas said. “It’s divisive and confrontational often, when it should be collaborative. So this document, at this time, was serendipitous but wonderful timing.”

The 2022 ACC Health Policy Statement on Building Respect, Civility, and Inclusion in the Cardiovascular Workforce was published online March 17 in the Journal of the American College of Cardiology.

The 63-page document provides 12 principles for building a better workplace, starting with the belief that civil behavior and respect are inherent in its core values of teamwork, collaboration, and professionalism.

The ACC calls on all organizations and individuals involved in providing cardiovascular care, education, or research to recognize the “ubiquity” of uncivil behavior and the continuum of bias, discrimination, bullying, and harassment (BDBH) that characterize it.

Some of the recommendations they offer to eliminate these behaviors include:

• Creating institutional policies and resources to ensure hiring decisions, evaluations, and departmental/program/center reviews are objective.
• Including assessments of personal behaviors related to respect and civility in performance reviews.
• Establishing confidential, fair, and transparent mechanisms for reporting and investigating individuals and/or departments suspected of BDBH.
• Adopting longitudinal metrics and accurate data collection to track progress and inform future policy and interventions.
• Encouraging independent evaluation of institutional culture and efforts to reduce BDBH.
• Celebrating those who promote and achieve excellence in reducing BDBH.

Patients behaving badly

What’s new, especially since the COVID-19 pandemic, is the number of patients who themselves engage in disrespectful and uncivil behavior, observed Dr. Douglas.

“As physicians, it was the patient’s always right. So you work to do backflips to accommodate the patient,” she said. “But when the patient says: I don’t want to be treated by anybody that comes from outside the United States, that’s not our society anymore. And that has to be addressed and dealt with.”

The policy statement features a suite of online tools and resources including 15 case examples and 30 sample policies from institutions that have been anonymized and some provide an action framework for addressing this type of patient behavior, Dr. Douglas said. An individual, for example, can ask the patient why they made the remark, explaining that the provider is qualified and someone they’d like to have care for their own family. If it was a trainee on the receiving end, it’s fair for them to go back to their supervisor, mentor, or training director.

“They should back you up and explain to the patient that it’s not who we are at this hospital and that they’re happy to provide care, but they are part of the hospital and need to obey the rules and environment in this hospital,” she said.

Writing committee cochair Michael J. Mack, MD, of Baylor Scott & White Health, Plano, Tex., told tthis news organization that “one of the concepts that I hadn’t heard before that resonated with me was the term ‘upstander’ – that you can’t just be a bystander and watch this happen and do nothing. If you’re witness to this in the workplace, if it’s gender bias or racial bias, you need to get involved and reach out to that individual and see what you can do to help and be a reporter of it.”
 

But it’s all too costly

Financial constraints are often cited as a reason not to focus on bias, discrimination, bullying, and harassment in the workplace or to shelve initiatives, but it’s a false argument, say Dr. Mack and Dr. Douglas.

“One of the case examples is a cardiology practice that is suffering a decline in finances, and the board makes the recommendation that the efforts at diversity and civil workplaces need to be the first to go,” Dr. Mack explained. “And the point that’s being made in this is you can’t afford not to do it because it ends up being more costly to the business in the long run.”

Part of that cost is associated with losing valuable employees that were contributing but left because there wasn’t a culture of respectfulness and positivity in their workplace. While that’s always been a risk, it’s become a particularly compelling issue because of the workforce shortages present 3 years on in the pandemic, he said.

“There’s a new reexamination to be sure that we have a positive work environment that people want to come to work at every day,” he said. “I run our Research Institute, and normally we have a 5% vacancy rate, and our unfilled-position rate is 25% right now.”

Health care is delivered as a team today, but if a member feels disrespected, or worse – harassed, bullied, or discriminated against – they’re not going to contribute at the top of their game, Dr. Douglas said.

“It’s very well documented that bad behavior exists and that it has negative consequences for patient care for institutions, who are at great risk legally and regulatory wise,” she said. “And the document makes that clear that that risk is increasing.”

Dr. Douglas pointed out that the Joint Commission now requires good behavior in institutions that it accredits and that the Accreditation Council for Graduate Medical Education requires education around professionalism and evidence that their trainees are treated as professionals.

Funding agencies like the National Institutes of Health have also jumped into this space, recently establishing a hotline to report harassment, discrimination, and bullying perpetrated by an NIH-funded investigator, and giving institutions 30 days to investigate.

“In the last 2 years they have defunded, taken away the grants of 75 investigators, compared to zero in the 5 years before that,” Dr. Douglas said. “So I think, even though the bad behavior may be escalating, the consequences are escalating too.”

The new “2022 ACC Health Policy Statement on Building Respect, Civility, and Inclusion in the Cardiovascular Workplace” will be discussed in a session at the ACC 2022 Scientific Sessions on April 2 at 4:15 p.m. ET.

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

The American College of Cardiology has issued a new health policy statement directed at eliminating the bias, discrimination, bullying, and harassment that hamstrings the delivery of quality cardiovascular care.

“We pay a lot of attention, of course, to our patients and patient care issues but our ability to care optimally for patients is limited if the workforce is handicapped in any way,” said Pamela S. Douglas, MD, of Duke University, Durham, N.C., who cochaired the writing committee.

The document is the second in the ACC’s diversity inclusion initiative, following the 2019 report on equal compensation and opportunity in cardiology, but the foundation for the work actually started 5 years ago, she told this news organization.

“Unfortunately, COVID and other world events have created a climate in the United States where people don’t treat each other terribly well,” Dr. Douglas said. “It’s divisive and confrontational often, when it should be collaborative. So this document, at this time, was serendipitous but wonderful timing.”

The 2022 ACC Health Policy Statement on Building Respect, Civility, and Inclusion in the Cardiovascular Workforce was published online March 17 in the Journal of the American College of Cardiology.

The 63-page document provides 12 principles for building a better workplace, starting with the belief that civil behavior and respect are inherent in its core values of teamwork, collaboration, and professionalism.

The ACC calls on all organizations and individuals involved in providing cardiovascular care, education, or research to recognize the “ubiquity” of uncivil behavior and the continuum of bias, discrimination, bullying, and harassment (BDBH) that characterize it.

Some of the recommendations they offer to eliminate these behaviors include:

• Creating institutional policies and resources to ensure hiring decisions, evaluations, and departmental/program/center reviews are objective.
• Including assessments of personal behaviors related to respect and civility in performance reviews.
• Establishing confidential, fair, and transparent mechanisms for reporting and investigating individuals and/or departments suspected of BDBH.
• Adopting longitudinal metrics and accurate data collection to track progress and inform future policy and interventions.
• Encouraging independent evaluation of institutional culture and efforts to reduce BDBH.
• Celebrating those who promote and achieve excellence in reducing BDBH.

Patients behaving badly

What’s new, especially since the COVID-19 pandemic, is the number of patients who themselves engage in disrespectful and uncivil behavior, observed Dr. Douglas.

“As physicians, it was the patient’s always right. So you work to do backflips to accommodate the patient,” she said. “But when the patient says: I don’t want to be treated by anybody that comes from outside the United States, that’s not our society anymore. And that has to be addressed and dealt with.”

The policy statement features a suite of online tools and resources including 15 case examples and 30 sample policies from institutions that have been anonymized and some provide an action framework for addressing this type of patient behavior, Dr. Douglas said. An individual, for example, can ask the patient why they made the remark, explaining that the provider is qualified and someone they’d like to have care for their own family. If it was a trainee on the receiving end, it’s fair for them to go back to their supervisor, mentor, or training director.

“They should back you up and explain to the patient that it’s not who we are at this hospital and that they’re happy to provide care, but they are part of the hospital and need to obey the rules and environment in this hospital,” she said.

Writing committee cochair Michael J. Mack, MD, of Baylor Scott & White Health, Plano, Tex., told tthis news organization that “one of the concepts that I hadn’t heard before that resonated with me was the term ‘upstander’ – that you can’t just be a bystander and watch this happen and do nothing. If you’re witness to this in the workplace, if it’s gender bias or racial bias, you need to get involved and reach out to that individual and see what you can do to help and be a reporter of it.”
 

But it’s all too costly

Financial constraints are often cited as a reason not to focus on bias, discrimination, bullying, and harassment in the workplace or to shelve initiatives, but it’s a false argument, say Dr. Mack and Dr. Douglas.

“One of the case examples is a cardiology practice that is suffering a decline in finances, and the board makes the recommendation that the efforts at diversity and civil workplaces need to be the first to go,” Dr. Mack explained. “And the point that’s being made in this is you can’t afford not to do it because it ends up being more costly to the business in the long run.”

Part of that cost is associated with losing valuable employees that were contributing but left because there wasn’t a culture of respectfulness and positivity in their workplace. While that’s always been a risk, it’s become a particularly compelling issue because of the workforce shortages present 3 years on in the pandemic, he said.

“There’s a new reexamination to be sure that we have a positive work environment that people want to come to work at every day,” he said. “I run our Research Institute, and normally we have a 5% vacancy rate, and our unfilled-position rate is 25% right now.”

Health care is delivered as a team today, but if a member feels disrespected, or worse – harassed, bullied, or discriminated against – they’re not going to contribute at the top of their game, Dr. Douglas said.

“It’s very well documented that bad behavior exists and that it has negative consequences for patient care for institutions, who are at great risk legally and regulatory wise,” she said. “And the document makes that clear that that risk is increasing.”

Dr. Douglas pointed out that the Joint Commission now requires good behavior in institutions that it accredits and that the Accreditation Council for Graduate Medical Education requires education around professionalism and evidence that their trainees are treated as professionals.

Funding agencies like the National Institutes of Health have also jumped into this space, recently establishing a hotline to report harassment, discrimination, and bullying perpetrated by an NIH-funded investigator, and giving institutions 30 days to investigate.

“In the last 2 years they have defunded, taken away the grants of 75 investigators, compared to zero in the 5 years before that,” Dr. Douglas said. “So I think, even though the bad behavior may be escalating, the consequences are escalating too.”

The new “2022 ACC Health Policy Statement on Building Respect, Civility, and Inclusion in the Cardiovascular Workplace” will be discussed in a session at the ACC 2022 Scientific Sessions on April 2 at 4:15 p.m. ET.

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

The American College of Cardiology has issued a new health policy statement directed at eliminating the bias, discrimination, bullying, and harassment that hamstrings the delivery of quality cardiovascular care.

“We pay a lot of attention, of course, to our patients and patient care issues but our ability to care optimally for patients is limited if the workforce is handicapped in any way,” said Pamela S. Douglas, MD, of Duke University, Durham, N.C., who cochaired the writing committee.

The document is the second in the ACC’s diversity inclusion initiative, following the 2019 report on equal compensation and opportunity in cardiology, but the foundation for the work actually started 5 years ago, she told this news organization.

“Unfortunately, COVID and other world events have created a climate in the United States where people don’t treat each other terribly well,” Dr. Douglas said. “It’s divisive and confrontational often, when it should be collaborative. So this document, at this time, was serendipitous but wonderful timing.”

The 2022 ACC Health Policy Statement on Building Respect, Civility, and Inclusion in the Cardiovascular Workforce was published online March 17 in the Journal of the American College of Cardiology.

The 63-page document provides 12 principles for building a better workplace, starting with the belief that civil behavior and respect are inherent in its core values of teamwork, collaboration, and professionalism.

The ACC calls on all organizations and individuals involved in providing cardiovascular care, education, or research to recognize the “ubiquity” of uncivil behavior and the continuum of bias, discrimination, bullying, and harassment (BDBH) that characterize it.

Some of the recommendations they offer to eliminate these behaviors include:

• Creating institutional policies and resources to ensure hiring decisions, evaluations, and departmental/program/center reviews are objective.
• Including assessments of personal behaviors related to respect and civility in performance reviews.
• Establishing confidential, fair, and transparent mechanisms for reporting and investigating individuals and/or departments suspected of BDBH.
• Adopting longitudinal metrics and accurate data collection to track progress and inform future policy and interventions.
• Encouraging independent evaluation of institutional culture and efforts to reduce BDBH.
• Celebrating those who promote and achieve excellence in reducing BDBH.

Patients behaving badly

What’s new, especially since the COVID-19 pandemic, is the number of patients who themselves engage in disrespectful and uncivil behavior, observed Dr. Douglas.

“As physicians, it was the patient’s always right. So you work to do backflips to accommodate the patient,” she said. “But when the patient says: I don’t want to be treated by anybody that comes from outside the United States, that’s not our society anymore. And that has to be addressed and dealt with.”

The policy statement features a suite of online tools and resources including 15 case examples and 30 sample policies from institutions that have been anonymized and some provide an action framework for addressing this type of patient behavior, Dr. Douglas said. An individual, for example, can ask the patient why they made the remark, explaining that the provider is qualified and someone they’d like to have care for their own family. If it was a trainee on the receiving end, it’s fair for them to go back to their supervisor, mentor, or training director.

“They should back you up and explain to the patient that it’s not who we are at this hospital and that they’re happy to provide care, but they are part of the hospital and need to obey the rules and environment in this hospital,” she said.

Writing committee cochair Michael J. Mack, MD, of Baylor Scott & White Health, Plano, Tex., told tthis news organization that “one of the concepts that I hadn’t heard before that resonated with me was the term ‘upstander’ – that you can’t just be a bystander and watch this happen and do nothing. If you’re witness to this in the workplace, if it’s gender bias or racial bias, you need to get involved and reach out to that individual and see what you can do to help and be a reporter of it.”
 

But it’s all too costly

Financial constraints are often cited as a reason not to focus on bias, discrimination, bullying, and harassment in the workplace or to shelve initiatives, but it’s a false argument, say Dr. Mack and Dr. Douglas.

“One of the case examples is a cardiology practice that is suffering a decline in finances, and the board makes the recommendation that the efforts at diversity and civil workplaces need to be the first to go,” Dr. Mack explained. “And the point that’s being made in this is you can’t afford not to do it because it ends up being more costly to the business in the long run.”

Part of that cost is associated with losing valuable employees that were contributing but left because there wasn’t a culture of respectfulness and positivity in their workplace. While that’s always been a risk, it’s become a particularly compelling issue because of the workforce shortages present 3 years on in the pandemic, he said.

“There’s a new reexamination to be sure that we have a positive work environment that people want to come to work at every day,” he said. “I run our Research Institute, and normally we have a 5% vacancy rate, and our unfilled-position rate is 25% right now.”

Health care is delivered as a team today, but if a member feels disrespected, or worse – harassed, bullied, or discriminated against – they’re not going to contribute at the top of their game, Dr. Douglas said.

“It’s very well documented that bad behavior exists and that it has negative consequences for patient care for institutions, who are at great risk legally and regulatory wise,” she said. “And the document makes that clear that that risk is increasing.”

Dr. Douglas pointed out that the Joint Commission now requires good behavior in institutions that it accredits and that the Accreditation Council for Graduate Medical Education requires education around professionalism and evidence that their trainees are treated as professionals.

Funding agencies like the National Institutes of Health have also jumped into this space, recently establishing a hotline to report harassment, discrimination, and bullying perpetrated by an NIH-funded investigator, and giving institutions 30 days to investigate.

“In the last 2 years they have defunded, taken away the grants of 75 investigators, compared to zero in the 5 years before that,” Dr. Douglas said. “So I think, even though the bad behavior may be escalating, the consequences are escalating too.”

The new “2022 ACC Health Policy Statement on Building Respect, Civility, and Inclusion in the Cardiovascular Workplace” will be discussed in a session at the ACC 2022 Scientific Sessions on April 2 at 4:15 p.m. ET.

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

All Kawasaki disease (KD) patients should be treated first with intravenous immunoglobulin, according to an updated guideline issued jointly by the American College of Rheumatology and the Vasculitis Foundation.

KD has low mortality when treated appropriately, guideline first author Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, and colleagues wrote.

The update is important at this time because new evidence continues to emerge in the clinical management of KD, Dr. Gorelik said in an interview.

“In addition, this guideline approaches Kawasaki disease from a perspective of acting as an adjunct to the already existing and excellent American Heart Association guidelines by adding information in areas that rheumatologists may play a role,” Dr. Gorelik said. “This is specifically regarding patients who may require additional therapy beyond standard IVIg, such as patients who may be at higher risk of morbidity from disease and patients who have refractory disease,” he explained.

The guideline, published in Arthritis & Rheumatology, includes 11 recommendations, 1 good practice statement, and 1 ungraded position statement. The good practice statement emphasizes that all patients with KD should be initially treated with IVIg.

The position statement advises that either nonglucocorticoid immunosuppressive therapy or glucocorticoids may be used for patients with acute KD whose fever persists despite repeated IVIg treatment. No clinical evidence currently supports the superiority of either nonglucocorticoid immunosuppressive therapy or glucocorticoids; therefore, the authors support the use of either based on what is appropriate in any given clinical situation. Although optimal dosage and duration of glucocorticoids have yet to be determined in a U.S. population, the authors described a typical glucocorticoid dosage as starting prednisone at 2 mg/kg per day, with a maximum of 60 mg/day, and dose tapering over 15 days.

The 11 recommendations consist of 7 strong and 4 conditional recommendations. The strong recommendations focus on prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in patients with unexplained macrophage activation syndrome or shock. The conditional recommendations support using established therapy promptly at disease onset, then identifying cases in which additional therapy is needed.

Dr. Gorelik highlighted four clinical takeaways from the guideline. First, “patients with higher risk for complications do exist in Kawasaki disease, and that these patients can be treated more aggressively,” he said. “Specifically, patients with aneurysms seen at first ultrasound, and patients who are under 6 months, are more likely to have progressive and/or refractory disease; these patients can be treated with an adjunctive short course of corticosteroids.”

Second, “the use of high-dose aspirin for patients with Kawasaki disease does not have strong basis in evidence. While aspirin itself of some dose is necessary for patients with Kawasaki disease, use of either high- or low-dose aspirin has the same outcome for patients, and a physician may choose either of these in practice,” he said.

Third, “we continue to recommend that refractory patients with Kawasaki disease be treated with a second dose of IVIg; however, there are many scenarios in which a physician may choose either corticosteroids [either a single high dose of >10 mg/kg, or a short moderate-dose course of 2 mg/kg per day for 5-7 days] or a biologic agent such as infliximab. ... These are valid choices for therapy in patients with refractory Kawasaki disease,” he emphasized.

Fourth, “physicians should discard the idea of treating before [and conversely, not treating after] 10 days of fever,” Dr. Gorelik said. “Patients with Kawasaki disease should be treated as soon as the diagnosis is made, regardless of whether this patient is on day 5, day 12, or day 20 of symptoms.”

Update incorporates emerging evidence

Potential barriers to implementing the guideline in practice include the challenge of weaning doctors from practices that are habitual in medicine, Dr. Gorelik said. “One of these is the use of high-dose aspirin for Kawasaki disease; a number of studies have shown over the past decade or more that high-dose aspirin has no greater effect than lower-dose aspirin for Kawasaki disease. Despite all of these studies, the use of high-dose aspirin continued. High-dose aspirin for Kawasaki disease was used in the era prior to use of IVIg as an anti-inflammatory agent. However, it has poor efficacy in this regard, and the true benefit for aspirin is for anticoagulation for patients at risk of a clot, and this is just as effective in lower doses. Expressing this in a guideline could help to change practices by helping physicians understand not only what they are guided to do, but why.”

Additional research is needed to better identify high-risk patients in non-Japanese populations, he noted. “While studies from Japan suggest that higher-risk patients can be identified based on various parameters, these have not been well replicated in non-Japanese populations. Good research that identifies which patients may be more at risk in other populations would be helpful to more precisely target high-risk therapy.”

Other research needs include a clearer understanding of the best therapies for refractory patients, Dr. Gorelik said. “One area of the most difficulty was determining whether patients with refractory disease should have repeated IVIg or a switch to glucocorticoids and biologic agents. Some of this research is underway, and some was published just as these guidelines were being drawn, and this particular area is one that is likely to change significantly. While currently we recommend a repeated dose of IVIg, it is likely that over the very near term, the use of repeated IVIg in KD will be curtailed” because of concerns such as the relatively high rate of hemolysis. Research to identify which therapy has a noninferior effect with a superior risk profile is needed; such research “will likely result in a future iteration of these guidelines specifically related to this question,” he concluded.

The KD guideline is the final companion to three additional ACR/VF vasculitis guidelines that were released in July 2021. The guideline research received no outside funding. The researchers had no financial conflicts to disclose.

All Kawasaki disease (KD) patients should be treated first with intravenous immunoglobulin, according to an updated guideline issued jointly by the American College of Rheumatology and the Vasculitis Foundation.

KD has low mortality when treated appropriately, guideline first author Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, and colleagues wrote.

The update is important at this time because new evidence continues to emerge in the clinical management of KD, Dr. Gorelik said in an interview.

“In addition, this guideline approaches Kawasaki disease from a perspective of acting as an adjunct to the already existing and excellent American Heart Association guidelines by adding information in areas that rheumatologists may play a role,” Dr. Gorelik said. “This is specifically regarding patients who may require additional therapy beyond standard IVIg, such as patients who may be at higher risk of morbidity from disease and patients who have refractory disease,” he explained.

The guideline, published in Arthritis & Rheumatology, includes 11 recommendations, 1 good practice statement, and 1 ungraded position statement. The good practice statement emphasizes that all patients with KD should be initially treated with IVIg.

The position statement advises that either nonglucocorticoid immunosuppressive therapy or glucocorticoids may be used for patients with acute KD whose fever persists despite repeated IVIg treatment. No clinical evidence currently supports the superiority of either nonglucocorticoid immunosuppressive therapy or glucocorticoids; therefore, the authors support the use of either based on what is appropriate in any given clinical situation. Although optimal dosage and duration of glucocorticoids have yet to be determined in a U.S. population, the authors described a typical glucocorticoid dosage as starting prednisone at 2 mg/kg per day, with a maximum of 60 mg/day, and dose tapering over 15 days.

The 11 recommendations consist of 7 strong and 4 conditional recommendations. The strong recommendations focus on prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in patients with unexplained macrophage activation syndrome or shock. The conditional recommendations support using established therapy promptly at disease onset, then identifying cases in which additional therapy is needed.

Dr. Gorelik highlighted four clinical takeaways from the guideline. First, “patients with higher risk for complications do exist in Kawasaki disease, and that these patients can be treated more aggressively,” he said. “Specifically, patients with aneurysms seen at first ultrasound, and patients who are under 6 months, are more likely to have progressive and/or refractory disease; these patients can be treated with an adjunctive short course of corticosteroids.”

Second, “the use of high-dose aspirin for patients with Kawasaki disease does not have strong basis in evidence. While aspirin itself of some dose is necessary for patients with Kawasaki disease, use of either high- or low-dose aspirin has the same outcome for patients, and a physician may choose either of these in practice,” he said.

Third, “we continue to recommend that refractory patients with Kawasaki disease be treated with a second dose of IVIg; however, there are many scenarios in which a physician may choose either corticosteroids [either a single high dose of >10 mg/kg, or a short moderate-dose course of 2 mg/kg per day for 5-7 days] or a biologic agent such as infliximab. ... These are valid choices for therapy in patients with refractory Kawasaki disease,” he emphasized.

Fourth, “physicians should discard the idea of treating before [and conversely, not treating after] 10 days of fever,” Dr. Gorelik said. “Patients with Kawasaki disease should be treated as soon as the diagnosis is made, regardless of whether this patient is on day 5, day 12, or day 20 of symptoms.”

Update incorporates emerging evidence

Potential barriers to implementing the guideline in practice include the challenge of weaning doctors from practices that are habitual in medicine, Dr. Gorelik said. “One of these is the use of high-dose aspirin for Kawasaki disease; a number of studies have shown over the past decade or more that high-dose aspirin has no greater effect than lower-dose aspirin for Kawasaki disease. Despite all of these studies, the use of high-dose aspirin continued. High-dose aspirin for Kawasaki disease was used in the era prior to use of IVIg as an anti-inflammatory agent. However, it has poor efficacy in this regard, and the true benefit for aspirin is for anticoagulation for patients at risk of a clot, and this is just as effective in lower doses. Expressing this in a guideline could help to change practices by helping physicians understand not only what they are guided to do, but why.”

Additional research is needed to better identify high-risk patients in non-Japanese populations, he noted. “While studies from Japan suggest that higher-risk patients can be identified based on various parameters, these have not been well replicated in non-Japanese populations. Good research that identifies which patients may be more at risk in other populations would be helpful to more precisely target high-risk therapy.”

Other research needs include a clearer understanding of the best therapies for refractory patients, Dr. Gorelik said. “One area of the most difficulty was determining whether patients with refractory disease should have repeated IVIg or a switch to glucocorticoids and biologic agents. Some of this research is underway, and some was published just as these guidelines were being drawn, and this particular area is one that is likely to change significantly. While currently we recommend a repeated dose of IVIg, it is likely that over the very near term, the use of repeated IVIg in KD will be curtailed” because of concerns such as the relatively high rate of hemolysis. Research to identify which therapy has a noninferior effect with a superior risk profile is needed; such research “will likely result in a future iteration of these guidelines specifically related to this question,” he concluded.

The KD guideline is the final companion to three additional ACR/VF vasculitis guidelines that were released in July 2021. The guideline research received no outside funding. The researchers had no financial conflicts to disclose.

All Kawasaki disease (KD) patients should be treated first with intravenous immunoglobulin, according to an updated guideline issued jointly by the American College of Rheumatology and the Vasculitis Foundation.

KD has low mortality when treated appropriately, guideline first author Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, and colleagues wrote.

The update is important at this time because new evidence continues to emerge in the clinical management of KD, Dr. Gorelik said in an interview.

“In addition, this guideline approaches Kawasaki disease from a perspective of acting as an adjunct to the already existing and excellent American Heart Association guidelines by adding information in areas that rheumatologists may play a role,” Dr. Gorelik said. “This is specifically regarding patients who may require additional therapy beyond standard IVIg, such as patients who may be at higher risk of morbidity from disease and patients who have refractory disease,” he explained.

The guideline, published in Arthritis & Rheumatology, includes 11 recommendations, 1 good practice statement, and 1 ungraded position statement. The good practice statement emphasizes that all patients with KD should be initially treated with IVIg.

The position statement advises that either nonglucocorticoid immunosuppressive therapy or glucocorticoids may be used for patients with acute KD whose fever persists despite repeated IVIg treatment. No clinical evidence currently supports the superiority of either nonglucocorticoid immunosuppressive therapy or glucocorticoids; therefore, the authors support the use of either based on what is appropriate in any given clinical situation. Although optimal dosage and duration of glucocorticoids have yet to be determined in a U.S. population, the authors described a typical glucocorticoid dosage as starting prednisone at 2 mg/kg per day, with a maximum of 60 mg/day, and dose tapering over 15 days.

The 11 recommendations consist of 7 strong and 4 conditional recommendations. The strong recommendations focus on prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in patients with unexplained macrophage activation syndrome or shock. The conditional recommendations support using established therapy promptly at disease onset, then identifying cases in which additional therapy is needed.

Dr. Gorelik highlighted four clinical takeaways from the guideline. First, “patients with higher risk for complications do exist in Kawasaki disease, and that these patients can be treated more aggressively,” he said. “Specifically, patients with aneurysms seen at first ultrasound, and patients who are under 6 months, are more likely to have progressive and/or refractory disease; these patients can be treated with an adjunctive short course of corticosteroids.”

Second, “the use of high-dose aspirin for patients with Kawasaki disease does not have strong basis in evidence. While aspirin itself of some dose is necessary for patients with Kawasaki disease, use of either high- or low-dose aspirin has the same outcome for patients, and a physician may choose either of these in practice,” he said.

Third, “we continue to recommend that refractory patients with Kawasaki disease be treated with a second dose of IVIg; however, there are many scenarios in which a physician may choose either corticosteroids [either a single high dose of >10 mg/kg, or a short moderate-dose course of 2 mg/kg per day for 5-7 days] or a biologic agent such as infliximab. ... These are valid choices for therapy in patients with refractory Kawasaki disease,” he emphasized.

Fourth, “physicians should discard the idea of treating before [and conversely, not treating after] 10 days of fever,” Dr. Gorelik said. “Patients with Kawasaki disease should be treated as soon as the diagnosis is made, regardless of whether this patient is on day 5, day 12, or day 20 of symptoms.”

Update incorporates emerging evidence

Potential barriers to implementing the guideline in practice include the challenge of weaning doctors from practices that are habitual in medicine, Dr. Gorelik said. “One of these is the use of high-dose aspirin for Kawasaki disease; a number of studies have shown over the past decade or more that high-dose aspirin has no greater effect than lower-dose aspirin for Kawasaki disease. Despite all of these studies, the use of high-dose aspirin continued. High-dose aspirin for Kawasaki disease was used in the era prior to use of IVIg as an anti-inflammatory agent. However, it has poor efficacy in this regard, and the true benefit for aspirin is for anticoagulation for patients at risk of a clot, and this is just as effective in lower doses. Expressing this in a guideline could help to change practices by helping physicians understand not only what they are guided to do, but why.”

Additional research is needed to better identify high-risk patients in non-Japanese populations, he noted. “While studies from Japan suggest that higher-risk patients can be identified based on various parameters, these have not been well replicated in non-Japanese populations. Good research that identifies which patients may be more at risk in other populations would be helpful to more precisely target high-risk therapy.”

Other research needs include a clearer understanding of the best therapies for refractory patients, Dr. Gorelik said. “One area of the most difficulty was determining whether patients with refractory disease should have repeated IVIg or a switch to glucocorticoids and biologic agents. Some of this research is underway, and some was published just as these guidelines were being drawn, and this particular area is one that is likely to change significantly. While currently we recommend a repeated dose of IVIg, it is likely that over the very near term, the use of repeated IVIg in KD will be curtailed” because of concerns such as the relatively high rate of hemolysis. Research to identify which therapy has a noninferior effect with a superior risk profile is needed; such research “will likely result in a future iteration of these guidelines specifically related to this question,” he concluded.

The KD guideline is the final companion to three additional ACR/VF vasculitis guidelines that were released in July 2021. The guideline research received no outside funding. The researchers had no financial conflicts to disclose.

The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.

The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.

The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.

AlexLMX/Getty Images

“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”

The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine. 

“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
 

Myocarditis

The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.

It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.

The document makes the following recommendations in regard to COVID-related myocarditis:

When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.

Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.

Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.

As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.

The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.

But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.

In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
 

Long COVID

The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.

Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.

Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”

The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:

PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.

PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.

The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.

For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.

Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.

Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.

Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.

Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
 

Return to play for athletes

The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.

But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.

They make the following recommendations:

• For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
• For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
• Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
• For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
• For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.

Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.

Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.

The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.

“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.

The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.

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

The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.

The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.

The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.

AlexLMX/Getty Images

“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”

The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine. 

“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
 

Myocarditis

The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.

It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.

The document makes the following recommendations in regard to COVID-related myocarditis:

When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.

Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.

Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.

As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.

The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.

But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.

In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
 

Long COVID

The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.

Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.

Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”

The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:

PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.

PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.

The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.

For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.

Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.

Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.

Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.

Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
 

Return to play for athletes

The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.

But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.

They make the following recommendations:

• For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
• For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
• Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
• For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
• For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.

Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.

Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.

The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.

“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.

The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.

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

The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.

The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.

The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.

AlexLMX/Getty Images

“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”

The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine. 

“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
 

Myocarditis

The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.

It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.

The document makes the following recommendations in regard to COVID-related myocarditis:

When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.

Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.

Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.

As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.

The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.

But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.

In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
 

Long COVID

The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.

Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.

Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”

The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:

PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.

PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.

The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.

For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.

Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.

Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.

Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.

Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
 

Return to play for athletes

The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.

But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.

They make the following recommendations:

• For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
• For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
• Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
• For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
• For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.

Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.

Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.

The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.

“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.

The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.

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

The American Academy of Neurology (AAN) has released new expert guidance on palliative care for patients with stroke, dementia, Parkinson’s disease, and other neurologic disorders.

Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.

“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.

The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
 

Guidance across the lifespan

The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.

For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.

They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.

Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
 

Ethical considerations

When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.

The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.

When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.

Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.

The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.

In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.

Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.

These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
 

Stroke, dementia, Parkinson’s guidance

For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.

For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.

They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.

For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.

It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.

On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.

Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.

In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
 

Well-timed update

Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.

“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.

She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.

Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”

However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”

“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.

Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.

There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.

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

The American Academy of Neurology (AAN) has released new expert guidance on palliative care for patients with stroke, dementia, Parkinson’s disease, and other neurologic disorders.

Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.

“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.

The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
 

Guidance across the lifespan

The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.

For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.

They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.

Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
 

Ethical considerations

When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.

The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.

When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.

Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.

The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.

In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.

Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.

These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
 

Stroke, dementia, Parkinson’s guidance

For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.

For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.

They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.

For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.

It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.

On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.

Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.

In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
 

Well-timed update

Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.

“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.

She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.

Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”

However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”

“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.

Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.

There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.

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

The American Academy of Neurology (AAN) has released new expert guidance on palliative care for patients with stroke, dementia, Parkinson’s disease, and other neurologic disorders.

Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.

“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.

The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
 

Guidance across the lifespan

The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.

For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.

They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.

Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
 

Ethical considerations

When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.

The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.

When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.

Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.

The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.

In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.

Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.

These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
 

Stroke, dementia, Parkinson’s guidance

For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.

For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.

They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.

For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.

It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.

On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.

Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.

In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
 

Well-timed update

Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.

“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.

She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.

Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”

However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”

“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.

Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.

There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.

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

Treatment of systemic juvenile idiopathic arthritis (sJIA) should emphasize early use of conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), compared with the previous reliance on NSAIDs and glucocorticoids, according to new guidelines from the American College of Rheumatology. The recently published 2021 guidelines focus on therapeutic approaches for oligoarthritis, temporomandibular joint (TMJ) arthritis, and sJIA.

“Systemic JIA should be treated early with biologics to rapidly bring disease under control and to avoid long-term use of glucocorticoids,” Karen Onel, MD, chief of the division of pediatric rheumatology at Weill Cornell Medicine, New York, and lead author of the guidelines, told this news organization. “Unfortunately, biologics can and are frequently denied for first-line use. For this reason, the guidelines are critically important as they demonstrate that first-line use of biologics are standard of care for the treatment of sJIA.”

The new publication is the second part of the ACR’s process to update JIA guidelines that began in 2017 and complements the release in 2019 of guidelines on the management of nonsystemic polyarthritis, sacroiliitis, and enthesitis, as well as a separate guidance on JIA-associated uveitis. The new guidelines include a second publication focused on nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Both sets of guidelines grew out of a 15-member panel that included young adults with JIA and caregivers of children with JIA, and which required at least 70% agreement on recommendations.

“Though the scope of the two guidelines differed, one thing they had in common is the recognition of the importance of shared decision-making with the patient/caregiver,” Dr. Onel said. “Not every decision will be appropriate for every patient, which is why it was so instrumental to receive input from both patients and caregivers when creating these recommendations.”
 

Oligoarticular and TMJ arthritis

Oligoarticular and TMJ arthritis have similar recommendations, beginning with NSAIDs conditionally recommended and intra-articular glucocorticoids (IAGCs) strongly recommended as part of initial therapy. For oligoarticular arthritis, the guidelines specifically include a strong recommendation of triamcinolone hexacetonide as the preferred agent; no preferred agent is recommended for TMJ arthritis.

“The one thing that the panel was unanimous about was the use of triamcinolone hexacetonide for intra-articular steroid injections in oligoarticular kids,” Susan Shenoi, MBBS, MS, an associate professor and clinical director of pediatric rheumatology at Seattle Children’s Hospital and Research Center, said in an interview. “Triamcinolone hexacetonide has not been available recently, and through advocacy efforts, there is now a pathway to get that medication,” added Dr. Shenoi, a coauthor on the guidelines.

Dr. Onel said that “triamcinolone hexacetonide has been shown to be superior to alternative injectable glucocorticoids in achieving and maintaining remission in children with JIA,” but its unavailability meant physicians had to consider less effective, more potent, or more costly alternatives.” To address the shortage, “the FDA allowed the importation of one particular formulation of triamcinolone hexacetonide [Hexatrione 2%] specifically for joint injections in patients with JIA.”

The guidelines conditionally recommend against oral glucocorticoids for initial therapy for both oligoarticular and TMJ arthritis. In fact, throughout the guidelines it’s clear that the authors emphasize using steroids as little as possible, Dr. Shenoi said.

“Steroids are great anti-inflammatories, but in kids we worry about the long-term effects on growth and metabolism, and now we have many more DMARDs available,” Dr. Shenoi said.

The guidelines strongly recommend conventional synthetic DMARDs for patients with either of these diseases who cannot tolerate or do not respond to NSAIDs or IAGCs, with methotrexate conditionally recommended over leflunomide (Arava) for TMJ and over leflunomide, sulfasalazine (Azulfidine, Sulfazine), and hydroxychloroquine, respectively, for oligoarticular arthritis.

“NSAIDs remain widely used despite evidence supporting early use of DMARDs,” Dr. Onel said. “NSAIDs are readily available and familiar; however, they will not prevent disease progression. These guidelines should encourage short courses of NSAIDs only.”

If patients do not respond to or cannot tolerate NSAIDs, IAGCs, and at least one conventional DMARD, the guidelines strongly recommend a biologic DMARD for oligoarticular arthritis and conditionally recommend one for TMJ arthritis, without any preferences to the specific agent.

The guidelines also advise using validated disease activity measures to guide treatment decisions.

“The most important thing when you’re looking at these patients is to determine, do they have active disease or not?” Dr. Shenoi said. “If they have active disease, then you really want to step up therapy.” Using the relatively new concept of treat-to-target, Dr. Shenoi added that a crucial part of shared decision-making with the family is identifying the most appropriate target for that family “and then really trying hard to achieve that target.”

The guidelines also list risk factors for poor outcome that can be used to guide treatment decisions.

“Specific involvement of key joints, such as TMJ, wrist, sacroiliac, hip, and ankle, and other features were considered reasonable justification for early escalation of therapy,” Dr. Onel said. Other features included presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, and symmetric disease. “Moving quickly may be needed for a patient who is rapidly worsening, while moving slower may be appropriate for somebody who has improved substantially, but not fully.”

Systemic JIA with and without macrophage activation syndrome

For systemic JIA without macrophage activation syndrome (MAS), the guidelines similarly advise against oral glucocorticoids as initial monotherapy while conditionally recommending NSAIDs for initial monotherapy. Where the guidelines differ most from those for oligoarticular and TMJ arthritis is in progression of DMARD use, with a strong recommendation against conventional synthetic DMARDs as an initial monotherapy and interleukin-1 and IL-6 inhibitors conditionally recommended for initial monotherapy.

For patients who don’t adequately respond to NSAIDs or glucocorticoids, IL-1 and IL-6 inhibitors are strongly recommended over a single or combination of conventional DMARDs. Residual arthritis or an incomplete response to IL-1 or IL-6 inhibitors should lead next to biologic or conventional DMARDs instead of long-term glucocorticoids.

For patients with MAS, the guidelines conditionally recommend IL-1 and IL-6 inhibitors over calcineurin inhibitor monotherapy to reach inactive disease and MAS resolution, with glucocorticoids conditionally recommended in initial treatment. Again, however, for patients with incomplete responses to IL-1 or IL-6 inhibitors or with residual arthritis, the guidelines advise biologic or conventional DMARDs over long-term glucocorticoids.

In patients with sJIA with or without a history of MAS who have inactive disease, practitioners should taper and discontinue glucocorticoids (a strong recommendation). A conditional recommendation for tapering and discontinuing biologic DMARDs follows attainment of inactive disease.

Beyond pharmacology

Although many of the nonpharmacologic recommendations did not have strong evidence based on assessment with Grading of Recommendations Assessment, Development, and Evaluation methodology, consensus was more often the case than not, Dr. Onel said, such as with vaccination.

“There was strong support for the use of immunizations in children with JIA and specific guidance for children with JIA receiving immunosuppression, not on immunosuppression, and children who are underimmunized or unimmunized,” she said. “Although the supportive evidence was very low as per GRADE, panel members were strongly in favor [of immunizations], given risk of infection for immunosuppressed children as well as the preponderance of evidence in similar disease states, such as IBD [inflammatory bowel disease].”

An area with less consensus was whether to check antibody titers for vaccine-preventable childhood infections before beginning immunosuppressive medication, but more panelists opposed the practice than supported it, Dr. Onel said.

“Some panelists felt that the information might be useful for risk management in case of an outbreak or exposure,” she said. “Most believed that screening a fully immunized child was of low benefit and might delay treatment and incur unnecessary cost.”

The process of developing the documents also reveals where the biggest gaps are in research. 

“One of the things that we should strive for in the future is really to do more systematic studies so we have better quality of evidence going forward,” Dr. Shenoi said. Overall, however, the guidelines also reveal the progress made in treatment of JIA.

“We now know some of the key cytokines that are involved in the disease pathogenesis, and we have effective therapies for some of these pathways,” Dr. Shenoi said. “We used to use a lot more toxic medication for systemic JIA, and in past decades, these patients used to be on steroids forever. Now we have targeted therapies, and we have some patients who don’t ever need steroids because people are moving toward targeted therapies and having good results. That’s a huge step forward in the field.”

The research was funded by the ACR. Dr. Shenoi has been a consultant for Pfizer. Dr. Onel disclosed no relevant financial relationships.

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

Treatment of systemic juvenile idiopathic arthritis (sJIA) should emphasize early use of conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), compared with the previous reliance on NSAIDs and glucocorticoids, according to new guidelines from the American College of Rheumatology. The recently published 2021 guidelines focus on therapeutic approaches for oligoarthritis, temporomandibular joint (TMJ) arthritis, and sJIA.

“Systemic JIA should be treated early with biologics to rapidly bring disease under control and to avoid long-term use of glucocorticoids,” Karen Onel, MD, chief of the division of pediatric rheumatology at Weill Cornell Medicine, New York, and lead author of the guidelines, told this news organization. “Unfortunately, biologics can and are frequently denied for first-line use. For this reason, the guidelines are critically important as they demonstrate that first-line use of biologics are standard of care for the treatment of sJIA.”

The new publication is the second part of the ACR’s process to update JIA guidelines that began in 2017 and complements the release in 2019 of guidelines on the management of nonsystemic polyarthritis, sacroiliitis, and enthesitis, as well as a separate guidance on JIA-associated uveitis. The new guidelines include a second publication focused on nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Both sets of guidelines grew out of a 15-member panel that included young adults with JIA and caregivers of children with JIA, and which required at least 70% agreement on recommendations.

“Though the scope of the two guidelines differed, one thing they had in common is the recognition of the importance of shared decision-making with the patient/caregiver,” Dr. Onel said. “Not every decision will be appropriate for every patient, which is why it was so instrumental to receive input from both patients and caregivers when creating these recommendations.”
 

Oligoarticular and TMJ arthritis

Oligoarticular and TMJ arthritis have similar recommendations, beginning with NSAIDs conditionally recommended and intra-articular glucocorticoids (IAGCs) strongly recommended as part of initial therapy. For oligoarticular arthritis, the guidelines specifically include a strong recommendation of triamcinolone hexacetonide as the preferred agent; no preferred agent is recommended for TMJ arthritis.

“The one thing that the panel was unanimous about was the use of triamcinolone hexacetonide for intra-articular steroid injections in oligoarticular kids,” Susan Shenoi, MBBS, MS, an associate professor and clinical director of pediatric rheumatology at Seattle Children’s Hospital and Research Center, said in an interview. “Triamcinolone hexacetonide has not been available recently, and through advocacy efforts, there is now a pathway to get that medication,” added Dr. Shenoi, a coauthor on the guidelines.

Dr. Onel said that “triamcinolone hexacetonide has been shown to be superior to alternative injectable glucocorticoids in achieving and maintaining remission in children with JIA,” but its unavailability meant physicians had to consider less effective, more potent, or more costly alternatives.” To address the shortage, “the FDA allowed the importation of one particular formulation of triamcinolone hexacetonide [Hexatrione 2%] specifically for joint injections in patients with JIA.”

The guidelines conditionally recommend against oral glucocorticoids for initial therapy for both oligoarticular and TMJ arthritis. In fact, throughout the guidelines it’s clear that the authors emphasize using steroids as little as possible, Dr. Shenoi said.

“Steroids are great anti-inflammatories, but in kids we worry about the long-term effects on growth and metabolism, and now we have many more DMARDs available,” Dr. Shenoi said.

The guidelines strongly recommend conventional synthetic DMARDs for patients with either of these diseases who cannot tolerate or do not respond to NSAIDs or IAGCs, with methotrexate conditionally recommended over leflunomide (Arava) for TMJ and over leflunomide, sulfasalazine (Azulfidine, Sulfazine), and hydroxychloroquine, respectively, for oligoarticular arthritis.

“NSAIDs remain widely used despite evidence supporting early use of DMARDs,” Dr. Onel said. “NSAIDs are readily available and familiar; however, they will not prevent disease progression. These guidelines should encourage short courses of NSAIDs only.”

If patients do not respond to or cannot tolerate NSAIDs, IAGCs, and at least one conventional DMARD, the guidelines strongly recommend a biologic DMARD for oligoarticular arthritis and conditionally recommend one for TMJ arthritis, without any preferences to the specific agent.

The guidelines also advise using validated disease activity measures to guide treatment decisions.

“The most important thing when you’re looking at these patients is to determine, do they have active disease or not?” Dr. Shenoi said. “If they have active disease, then you really want to step up therapy.” Using the relatively new concept of treat-to-target, Dr. Shenoi added that a crucial part of shared decision-making with the family is identifying the most appropriate target for that family “and then really trying hard to achieve that target.”

The guidelines also list risk factors for poor outcome that can be used to guide treatment decisions.

“Specific involvement of key joints, such as TMJ, wrist, sacroiliac, hip, and ankle, and other features were considered reasonable justification for early escalation of therapy,” Dr. Onel said. Other features included presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, and symmetric disease. “Moving quickly may be needed for a patient who is rapidly worsening, while moving slower may be appropriate for somebody who has improved substantially, but not fully.”

Systemic JIA with and without macrophage activation syndrome

For systemic JIA without macrophage activation syndrome (MAS), the guidelines similarly advise against oral glucocorticoids as initial monotherapy while conditionally recommending NSAIDs for initial monotherapy. Where the guidelines differ most from those for oligoarticular and TMJ arthritis is in progression of DMARD use, with a strong recommendation against conventional synthetic DMARDs as an initial monotherapy and interleukin-1 and IL-6 inhibitors conditionally recommended for initial monotherapy.

For patients who don’t adequately respond to NSAIDs or glucocorticoids, IL-1 and IL-6 inhibitors are strongly recommended over a single or combination of conventional DMARDs. Residual arthritis or an incomplete response to IL-1 or IL-6 inhibitors should lead next to biologic or conventional DMARDs instead of long-term glucocorticoids.

For patients with MAS, the guidelines conditionally recommend IL-1 and IL-6 inhibitors over calcineurin inhibitor monotherapy to reach inactive disease and MAS resolution, with glucocorticoids conditionally recommended in initial treatment. Again, however, for patients with incomplete responses to IL-1 or IL-6 inhibitors or with residual arthritis, the guidelines advise biologic or conventional DMARDs over long-term glucocorticoids.

In patients with sJIA with or without a history of MAS who have inactive disease, practitioners should taper and discontinue glucocorticoids (a strong recommendation). A conditional recommendation for tapering and discontinuing biologic DMARDs follows attainment of inactive disease.

Beyond pharmacology

Although many of the nonpharmacologic recommendations did not have strong evidence based on assessment with Grading of Recommendations Assessment, Development, and Evaluation methodology, consensus was more often the case than not, Dr. Onel said, such as with vaccination.

“There was strong support for the use of immunizations in children with JIA and specific guidance for children with JIA receiving immunosuppression, not on immunosuppression, and children who are underimmunized or unimmunized,” she said. “Although the supportive evidence was very low as per GRADE, panel members were strongly in favor [of immunizations], given risk of infection for immunosuppressed children as well as the preponderance of evidence in similar disease states, such as IBD [inflammatory bowel disease].”

An area with less consensus was whether to check antibody titers for vaccine-preventable childhood infections before beginning immunosuppressive medication, but more panelists opposed the practice than supported it, Dr. Onel said.

“Some panelists felt that the information might be useful for risk management in case of an outbreak or exposure,” she said. “Most believed that screening a fully immunized child was of low benefit and might delay treatment and incur unnecessary cost.”

The process of developing the documents also reveals where the biggest gaps are in research. 

“One of the things that we should strive for in the future is really to do more systematic studies so we have better quality of evidence going forward,” Dr. Shenoi said. Overall, however, the guidelines also reveal the progress made in treatment of JIA.

“We now know some of the key cytokines that are involved in the disease pathogenesis, and we have effective therapies for some of these pathways,” Dr. Shenoi said. “We used to use a lot more toxic medication for systemic JIA, and in past decades, these patients used to be on steroids forever. Now we have targeted therapies, and we have some patients who don’t ever need steroids because people are moving toward targeted therapies and having good results. That’s a huge step forward in the field.”

The research was funded by the ACR. Dr. Shenoi has been a consultant for Pfizer. Dr. Onel disclosed no relevant financial relationships.

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

Treatment of systemic juvenile idiopathic arthritis (sJIA) should emphasize early use of conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), compared with the previous reliance on NSAIDs and glucocorticoids, according to new guidelines from the American College of Rheumatology. The recently published 2021 guidelines focus on therapeutic approaches for oligoarthritis, temporomandibular joint (TMJ) arthritis, and sJIA.

“Systemic JIA should be treated early with biologics to rapidly bring disease under control and to avoid long-term use of glucocorticoids,” Karen Onel, MD, chief of the division of pediatric rheumatology at Weill Cornell Medicine, New York, and lead author of the guidelines, told this news organization. “Unfortunately, biologics can and are frequently denied for first-line use. For this reason, the guidelines are critically important as they demonstrate that first-line use of biologics are standard of care for the treatment of sJIA.”

The new publication is the second part of the ACR’s process to update JIA guidelines that began in 2017 and complements the release in 2019 of guidelines on the management of nonsystemic polyarthritis, sacroiliitis, and enthesitis, as well as a separate guidance on JIA-associated uveitis. The new guidelines include a second publication focused on nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Both sets of guidelines grew out of a 15-member panel that included young adults with JIA and caregivers of children with JIA, and which required at least 70% agreement on recommendations.

“Though the scope of the two guidelines differed, one thing they had in common is the recognition of the importance of shared decision-making with the patient/caregiver,” Dr. Onel said. “Not every decision will be appropriate for every patient, which is why it was so instrumental to receive input from both patients and caregivers when creating these recommendations.”
 

Oligoarticular and TMJ arthritis

Oligoarticular and TMJ arthritis have similar recommendations, beginning with NSAIDs conditionally recommended and intra-articular glucocorticoids (IAGCs) strongly recommended as part of initial therapy. For oligoarticular arthritis, the guidelines specifically include a strong recommendation of triamcinolone hexacetonide as the preferred agent; no preferred agent is recommended for TMJ arthritis.

“The one thing that the panel was unanimous about was the use of triamcinolone hexacetonide for intra-articular steroid injections in oligoarticular kids,” Susan Shenoi, MBBS, MS, an associate professor and clinical director of pediatric rheumatology at Seattle Children’s Hospital and Research Center, said in an interview. “Triamcinolone hexacetonide has not been available recently, and through advocacy efforts, there is now a pathway to get that medication,” added Dr. Shenoi, a coauthor on the guidelines.

Dr. Onel said that “triamcinolone hexacetonide has been shown to be superior to alternative injectable glucocorticoids in achieving and maintaining remission in children with JIA,” but its unavailability meant physicians had to consider less effective, more potent, or more costly alternatives.” To address the shortage, “the FDA allowed the importation of one particular formulation of triamcinolone hexacetonide [Hexatrione 2%] specifically for joint injections in patients with JIA.”

The guidelines conditionally recommend against oral glucocorticoids for initial therapy for both oligoarticular and TMJ arthritis. In fact, throughout the guidelines it’s clear that the authors emphasize using steroids as little as possible, Dr. Shenoi said.

“Steroids are great anti-inflammatories, but in kids we worry about the long-term effects on growth and metabolism, and now we have many more DMARDs available,” Dr. Shenoi said.

The guidelines strongly recommend conventional synthetic DMARDs for patients with either of these diseases who cannot tolerate or do not respond to NSAIDs or IAGCs, with methotrexate conditionally recommended over leflunomide (Arava) for TMJ and over leflunomide, sulfasalazine (Azulfidine, Sulfazine), and hydroxychloroquine, respectively, for oligoarticular arthritis.

“NSAIDs remain widely used despite evidence supporting early use of DMARDs,” Dr. Onel said. “NSAIDs are readily available and familiar; however, they will not prevent disease progression. These guidelines should encourage short courses of NSAIDs only.”

If patients do not respond to or cannot tolerate NSAIDs, IAGCs, and at least one conventional DMARD, the guidelines strongly recommend a biologic DMARD for oligoarticular arthritis and conditionally recommend one for TMJ arthritis, without any preferences to the specific agent.

The guidelines also advise using validated disease activity measures to guide treatment decisions.

“The most important thing when you’re looking at these patients is to determine, do they have active disease or not?” Dr. Shenoi said. “If they have active disease, then you really want to step up therapy.” Using the relatively new concept of treat-to-target, Dr. Shenoi added that a crucial part of shared decision-making with the family is identifying the most appropriate target for that family “and then really trying hard to achieve that target.”

The guidelines also list risk factors for poor outcome that can be used to guide treatment decisions.

“Specific involvement of key joints, such as TMJ, wrist, sacroiliac, hip, and ankle, and other features were considered reasonable justification for early escalation of therapy,” Dr. Onel said. Other features included presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, and symmetric disease. “Moving quickly may be needed for a patient who is rapidly worsening, while moving slower may be appropriate for somebody who has improved substantially, but not fully.”

Systemic JIA with and without macrophage activation syndrome

For systemic JIA without macrophage activation syndrome (MAS), the guidelines similarly advise against oral glucocorticoids as initial monotherapy while conditionally recommending NSAIDs for initial monotherapy. Where the guidelines differ most from those for oligoarticular and TMJ arthritis is in progression of DMARD use, with a strong recommendation against conventional synthetic DMARDs as an initial monotherapy and interleukin-1 and IL-6 inhibitors conditionally recommended for initial monotherapy.

For patients who don’t adequately respond to NSAIDs or glucocorticoids, IL-1 and IL-6 inhibitors are strongly recommended over a single or combination of conventional DMARDs. Residual arthritis or an incomplete response to IL-1 or IL-6 inhibitors should lead next to biologic or conventional DMARDs instead of long-term glucocorticoids.

For patients with MAS, the guidelines conditionally recommend IL-1 and IL-6 inhibitors over calcineurin inhibitor monotherapy to reach inactive disease and MAS resolution, with glucocorticoids conditionally recommended in initial treatment. Again, however, for patients with incomplete responses to IL-1 or IL-6 inhibitors or with residual arthritis, the guidelines advise biologic or conventional DMARDs over long-term glucocorticoids.

In patients with sJIA with or without a history of MAS who have inactive disease, practitioners should taper and discontinue glucocorticoids (a strong recommendation). A conditional recommendation for tapering and discontinuing biologic DMARDs follows attainment of inactive disease.

Beyond pharmacology

Although many of the nonpharmacologic recommendations did not have strong evidence based on assessment with Grading of Recommendations Assessment, Development, and Evaluation methodology, consensus was more often the case than not, Dr. Onel said, such as with vaccination.

“There was strong support for the use of immunizations in children with JIA and specific guidance for children with JIA receiving immunosuppression, not on immunosuppression, and children who are underimmunized or unimmunized,” she said. “Although the supportive evidence was very low as per GRADE, panel members were strongly in favor [of immunizations], given risk of infection for immunosuppressed children as well as the preponderance of evidence in similar disease states, such as IBD [inflammatory bowel disease].”

An area with less consensus was whether to check antibody titers for vaccine-preventable childhood infections before beginning immunosuppressive medication, but more panelists opposed the practice than supported it, Dr. Onel said.

“Some panelists felt that the information might be useful for risk management in case of an outbreak or exposure,” she said. “Most believed that screening a fully immunized child was of low benefit and might delay treatment and incur unnecessary cost.”

The process of developing the documents also reveals where the biggest gaps are in research. 

“One of the things that we should strive for in the future is really to do more systematic studies so we have better quality of evidence going forward,” Dr. Shenoi said. Overall, however, the guidelines also reveal the progress made in treatment of JIA.

“We now know some of the key cytokines that are involved in the disease pathogenesis, and we have effective therapies for some of these pathways,” Dr. Shenoi said. “We used to use a lot more toxic medication for systemic JIA, and in past decades, these patients used to be on steroids forever. Now we have targeted therapies, and we have some patients who don’t ever need steroids because people are moving toward targeted therapies and having good results. That’s a huge step forward in the field.”

The research was funded by the ACR. Dr. Shenoi has been a consultant for Pfizer. Dr. Onel disclosed no relevant financial relationships.

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

A new expert commentary from the American Gastroenterological Association focuses on noninvasive screening options for colorectal cancer (CRC), as well as approaches to ensure quality in noninvasive screening programs. The commentary was published in Gastroenterology.

The American Cancer Society reported in its Cancer Facts & Figures 2021 report that lifetime risk of CRC in the United States is 4%, and those with above average risk are recommended to undergo CRC screening at an earlier age, with colonoscopy as a screening modality. Between 75% and 80% of the U.S. population is considered at average risk, and this is the group covered by the expert commentary. In this group, CRC rates jump from 35.1 to 61.2 cases per 100,000 people between the ages of 45-49 years and 50-54 years. Early-onset (before 50) CRC accounts for 12% of all cases and 7% of CRC-related deaths.

The authors noted that the U.S. Preventive Services Task Force made a grade B recommendation for individuals to begin screening at age 45, regardless of screening method, and their modeling suggests that screening initialization at 45 rather than 50 years increases life-years gained by 6.2% at the cost of a 17% increase in colonoscopies.

According to the commentary authors, a hybrid approach combining annual fecal immunochemical testing (FIT) at age 45-49, followed by colonoscopy between ages 50 and 70, could result in substantial gains in life-years while prioritizing colonoscopies for advancing age, which is associated with increased risk of advanced adenomas (AA) and CRC.
 

Exploring options

For stool-based CRC screening, FIT has generally replaced guaiac fecal occult blood testing because of better patient adherence and fewer restrictions on medicine and diet. FIT can produce a quantitative result measured in micrograms of hemoglobin per gram, or qualitatively positive above a threshold of 20 mcg per gram. The MTsDNA (Cologuard) test combines FIT with two DNA methylation markers, KRAS mutation screening, and a measurement of total human DNA, with use of an algorithm of combined results to determine positivity. It is approved only for average-risk individuals aged 45-85.

In cases where MTsDNA tests positive, but colonoscopy reveals no findings, an aerodigestive cancer could be present. However, this is considered rare based on a study that revealed that 2.4% of patients with discordant results developed an aerodigestive cancer during a median 5.4 years of follow-up, compared with 1.1% of cases with negative MTsDNA and negative colonoscopy. The difference was not statistically significant. The commentary authors suggest that no further testing is required after a negative high-quality colonoscopy and that patients can resume screening at normal intervals with any of the recommended tests.

The Septin 9 blood test (Epi proColon) is another screening option, and is FDA approved for average-risk individuals older than 50 years. It detects methylation of the promoter region of the Septin 9 gene. It has a 48% sensitivity and 91.5% specificity for CRC, as well as a sensitivity of 11.2% for AA. One model found that Septin 9 screening every 1 or 2 years could lead to more quality-adjusted life-years gained and prevention of more deaths than annual FIT, but with more colonoscopies. CRC screening guidelines do not endorse Septin 9, but screening studies are in progress to assess its performance.
 

Ensuring quality

“The linchpin for effective noninvasive screening programs is adherence, and several measures of adherence are required,” the authors wrote. To ensure high quality of noninvasive screening programs, it is important to create metrics and employ continuous monitoring of compliance, and to initiate changes when adherence and outcomes lag. Important metrics include patient compliance, rapid reporting of test results, timely implementation of follow-up colonoscopies, and systems put in place to restore patients to appropriate CRC screening intervals.

The authors suggested several specific metrics and attainable performance goals. The ratio of tests completed within 1 year to tests ordered should reach 90% or more. Outreach should be conducted to patients who do not complete testing within 1 month of the order. All patients should be contacted with 2 weeks of test results, and those who test negative should be made aware of the appropriate interval for future screening, along with the method of contact.

At least 80% of patients who receive a positive test should be offered a colonoscopy date within 3 months, and all within 6 months, because delay past that time is associated with greater risk of AA, CRC, and advanced-stage CRC. Within 6 months of a positive noninvasive test, at least 95% of patients should have undergone a colonoscopy, unless they are too ill, have moved, or cannot be reached. “Quality metrics for noninvasive screening programs should be set and program performance should be measured and ideally reported publicly,” the authors summarized. “Poor adherence at any level should trigger review of established protocols and facilitate change to ensure high-quality screening.”

Two authors disclosed relationships with Freenome and/or Check-Cap, but the third disclosed no conflicts.
 

A new expert commentary from the American Gastroenterological Association focuses on noninvasive screening options for colorectal cancer (CRC), as well as approaches to ensure quality in noninvasive screening programs. The commentary was published in Gastroenterology.

The American Cancer Society reported in its Cancer Facts & Figures 2021 report that lifetime risk of CRC in the United States is 4%, and those with above average risk are recommended to undergo CRC screening at an earlier age, with colonoscopy as a screening modality. Between 75% and 80% of the U.S. population is considered at average risk, and this is the group covered by the expert commentary. In this group, CRC rates jump from 35.1 to 61.2 cases per 100,000 people between the ages of 45-49 years and 50-54 years. Early-onset (before 50) CRC accounts for 12% of all cases and 7% of CRC-related deaths.

The authors noted that the U.S. Preventive Services Task Force made a grade B recommendation for individuals to begin screening at age 45, regardless of screening method, and their modeling suggests that screening initialization at 45 rather than 50 years increases life-years gained by 6.2% at the cost of a 17% increase in colonoscopies.

According to the commentary authors, a hybrid approach combining annual fecal immunochemical testing (FIT) at age 45-49, followed by colonoscopy between ages 50 and 70, could result in substantial gains in life-years while prioritizing colonoscopies for advancing age, which is associated with increased risk of advanced adenomas (AA) and CRC.
 

Exploring options

For stool-based CRC screening, FIT has generally replaced guaiac fecal occult blood testing because of better patient adherence and fewer restrictions on medicine and diet. FIT can produce a quantitative result measured in micrograms of hemoglobin per gram, or qualitatively positive above a threshold of 20 mcg per gram. The MTsDNA (Cologuard) test combines FIT with two DNA methylation markers, KRAS mutation screening, and a measurement of total human DNA, with use of an algorithm of combined results to determine positivity. It is approved only for average-risk individuals aged 45-85.

In cases where MTsDNA tests positive, but colonoscopy reveals no findings, an aerodigestive cancer could be present. However, this is considered rare based on a study that revealed that 2.4% of patients with discordant results developed an aerodigestive cancer during a median 5.4 years of follow-up, compared with 1.1% of cases with negative MTsDNA and negative colonoscopy. The difference was not statistically significant. The commentary authors suggest that no further testing is required after a negative high-quality colonoscopy and that patients can resume screening at normal intervals with any of the recommended tests.

The Septin 9 blood test (Epi proColon) is another screening option, and is FDA approved for average-risk individuals older than 50 years. It detects methylation of the promoter region of the Septin 9 gene. It has a 48% sensitivity and 91.5% specificity for CRC, as well as a sensitivity of 11.2% for AA. One model found that Septin 9 screening every 1 or 2 years could lead to more quality-adjusted life-years gained and prevention of more deaths than annual FIT, but with more colonoscopies. CRC screening guidelines do not endorse Septin 9, but screening studies are in progress to assess its performance.
 

Ensuring quality

“The linchpin for effective noninvasive screening programs is adherence, and several measures of adherence are required,” the authors wrote. To ensure high quality of noninvasive screening programs, it is important to create metrics and employ continuous monitoring of compliance, and to initiate changes when adherence and outcomes lag. Important metrics include patient compliance, rapid reporting of test results, timely implementation of follow-up colonoscopies, and systems put in place to restore patients to appropriate CRC screening intervals.

The authors suggested several specific metrics and attainable performance goals. The ratio of tests completed within 1 year to tests ordered should reach 90% or more. Outreach should be conducted to patients who do not complete testing within 1 month of the order. All patients should be contacted with 2 weeks of test results, and those who test negative should be made aware of the appropriate interval for future screening, along with the method of contact.

At least 80% of patients who receive a positive test should be offered a colonoscopy date within 3 months, and all within 6 months, because delay past that time is associated with greater risk of AA, CRC, and advanced-stage CRC. Within 6 months of a positive noninvasive test, at least 95% of patients should have undergone a colonoscopy, unless they are too ill, have moved, or cannot be reached. “Quality metrics for noninvasive screening programs should be set and program performance should be measured and ideally reported publicly,” the authors summarized. “Poor adherence at any level should trigger review of established protocols and facilitate change to ensure high-quality screening.”

Two authors disclosed relationships with Freenome and/or Check-Cap, but the third disclosed no conflicts.
 

A new expert commentary from the American Gastroenterological Association focuses on noninvasive screening options for colorectal cancer (CRC), as well as approaches to ensure quality in noninvasive screening programs. The commentary was published in Gastroenterology.

The American Cancer Society reported in its Cancer Facts & Figures 2021 report that lifetime risk of CRC in the United States is 4%, and those with above average risk are recommended to undergo CRC screening at an earlier age, with colonoscopy as a screening modality. Between 75% and 80% of the U.S. population is considered at average risk, and this is the group covered by the expert commentary. In this group, CRC rates jump from 35.1 to 61.2 cases per 100,000 people between the ages of 45-49 years and 50-54 years. Early-onset (before 50) CRC accounts for 12% of all cases and 7% of CRC-related deaths.

The authors noted that the U.S. Preventive Services Task Force made a grade B recommendation for individuals to begin screening at age 45, regardless of screening method, and their modeling suggests that screening initialization at 45 rather than 50 years increases life-years gained by 6.2% at the cost of a 17% increase in colonoscopies.

According to the commentary authors, a hybrid approach combining annual fecal immunochemical testing (FIT) at age 45-49, followed by colonoscopy between ages 50 and 70, could result in substantial gains in life-years while prioritizing colonoscopies for advancing age, which is associated with increased risk of advanced adenomas (AA) and CRC.
 

Exploring options

For stool-based CRC screening, FIT has generally replaced guaiac fecal occult blood testing because of better patient adherence and fewer restrictions on medicine and diet. FIT can produce a quantitative result measured in micrograms of hemoglobin per gram, or qualitatively positive above a threshold of 20 mcg per gram. The MTsDNA (Cologuard) test combines FIT with two DNA methylation markers, KRAS mutation screening, and a measurement of total human DNA, with use of an algorithm of combined results to determine positivity. It is approved only for average-risk individuals aged 45-85.

In cases where MTsDNA tests positive, but colonoscopy reveals no findings, an aerodigestive cancer could be present. However, this is considered rare based on a study that revealed that 2.4% of patients with discordant results developed an aerodigestive cancer during a median 5.4 years of follow-up, compared with 1.1% of cases with negative MTsDNA and negative colonoscopy. The difference was not statistically significant. The commentary authors suggest that no further testing is required after a negative high-quality colonoscopy and that patients can resume screening at normal intervals with any of the recommended tests.

The Septin 9 blood test (Epi proColon) is another screening option, and is FDA approved for average-risk individuals older than 50 years. It detects methylation of the promoter region of the Septin 9 gene. It has a 48% sensitivity and 91.5% specificity for CRC, as well as a sensitivity of 11.2% for AA. One model found that Septin 9 screening every 1 or 2 years could lead to more quality-adjusted life-years gained and prevention of more deaths than annual FIT, but with more colonoscopies. CRC screening guidelines do not endorse Septin 9, but screening studies are in progress to assess its performance.
 

Ensuring quality

“The linchpin for effective noninvasive screening programs is adherence, and several measures of adherence are required,” the authors wrote. To ensure high quality of noninvasive screening programs, it is important to create metrics and employ continuous monitoring of compliance, and to initiate changes when adherence and outcomes lag. Important metrics include patient compliance, rapid reporting of test results, timely implementation of follow-up colonoscopies, and systems put in place to restore patients to appropriate CRC screening intervals.

The authors suggested several specific metrics and attainable performance goals. The ratio of tests completed within 1 year to tests ordered should reach 90% or more. Outreach should be conducted to patients who do not complete testing within 1 month of the order. All patients should be contacted with 2 weeks of test results, and those who test negative should be made aware of the appropriate interval for future screening, along with the method of contact.

At least 80% of patients who receive a positive test should be offered a colonoscopy date within 3 months, and all within 6 months, because delay past that time is associated with greater risk of AA, CRC, and advanced-stage CRC. Within 6 months of a positive noninvasive test, at least 95% of patients should have undergone a colonoscopy, unless they are too ill, have moved, or cannot be reached. “Quality metrics for noninvasive screening programs should be set and program performance should be measured and ideally reported publicly,” the authors summarized. “Poor adherence at any level should trigger review of established protocols and facilitate change to ensure high-quality screening.”

Two authors disclosed relationships with Freenome and/or Check-Cap, but the third disclosed no conflicts.
 

New recommendations from the American Gastroenterological Association focus on choice of systemic therapy in hepatocellular carcinoma (HCC) patients. The guideline authors point out that prognosis and treatment decisions are both heavily dependent on a combination of the severity of underlying disease and biological characteristics of the tumor.

The document includes options for patients who are ineligible for locoregional therapy or resection, patients with metastatic disease and preserved liver function, patients with poor liver function, and patients receiving adjuvant therapy following surgery or locoregional therapy (LRT).

Intermediate or advanced tumor stage is common among HCC patients, and curative options such as surgery and ablation are generally limited to early-stage disease. LRTs – including transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and systemic therapy – may be employed against advanced or metastatic HCC, according to the authors, led by Grace L. Su, MD, of the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor, and the Veterans Affairs Ann Arbor Healthcare System.

In 2007, the Food and Drug Administration approved the multikinase inhibitor sorafenib as the first systemic therapy for HCC. The new guideline comes in the wake of new systemic therapeutic options that have arrived in the years since, including molecularly targeted therapy and immunotherapy. The authors of the guidance, published in Gastroenterology, include advice on both first- and second-line therapies.

Certainty of evidence for the recommendations ranges from low to very low, indicating limited or very little confidence in the effect estimated, and the true effect is likely to be considerably different than predicted by best current estimates. Accordingly, the recommendations are conditional, and decisions should be made with the values and preferences of the individual patient in mind.

In patients with preserved liver function who are ineligible for LRT or resection, or who have metastatic disease, the authors suggest that first-line treatment should be the combination of atezolizumab and bevacizumab rather than sorafenib. Bevacizumab comes with a bleeding risk, so patients should first be evaluated endoscopically and treated for esophageal varices. For patients who are ineligible for bevacizumab, alternatives are lenvatinib or sorafenib. Patients who are more concerned about disease progression than adverse events may want to consider lenvatinib rather than sorafenib, while those concerned about blood pressure control and who are less concerned about adverse skin reactions may choose sorafenib.

Options for second-line therapy after sorafenib include cabozantinib (mortality reduction, 2.2 months) and pembrolizumab (mortality reduction, 3.3 months). Patients with alpha-fetoprotein levels higher than 400 ng/mL may be candidates for treatment with ramucirumab (mortality reduction, 1.2 months). Another option is regorafenib (mortality reduction, 2.8 months). Patients who are more concerned about adverse effects than a potential survival benefit with any of these therapies may reasonably choose no systemic therapy.

For HCC patients with poor liver function, who are not eligible for LRT or resection, or with metastatic disease, the guidelines recommend against routine use of sorafenib.

In the setting of adjuvant therapy following curative surgical resection, curative local ablation, or TACE LRT, the guidelines recommend against the use of sorafenib. The authors also recommended against the use of bevacizumab following TACE LRT.

The authors noted that there is no high-quality comparative evidence in the second-line setting for atezolizumab plus bevacizumab, sorafenib, or lenvatinib. There is a dearth of evidence and few biomarkers to guide personalization of therapies, which places the emphasis on patient preferences, risks, and benefits.

The authors disclosed no conflicts.

New recommendations from the American Gastroenterological Association focus on choice of systemic therapy in hepatocellular carcinoma (HCC) patients. The guideline authors point out that prognosis and treatment decisions are both heavily dependent on a combination of the severity of underlying disease and biological characteristics of the tumor.

The document includes options for patients who are ineligible for locoregional therapy or resection, patients with metastatic disease and preserved liver function, patients with poor liver function, and patients receiving adjuvant therapy following surgery or locoregional therapy (LRT).

Intermediate or advanced tumor stage is common among HCC patients, and curative options such as surgery and ablation are generally limited to early-stage disease. LRTs – including transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and systemic therapy – may be employed against advanced or metastatic HCC, according to the authors, led by Grace L. Su, MD, of the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor, and the Veterans Affairs Ann Arbor Healthcare System.

In 2007, the Food and Drug Administration approved the multikinase inhibitor sorafenib as the first systemic therapy for HCC. The new guideline comes in the wake of new systemic therapeutic options that have arrived in the years since, including molecularly targeted therapy and immunotherapy. The authors of the guidance, published in Gastroenterology, include advice on both first- and second-line therapies.

Certainty of evidence for the recommendations ranges from low to very low, indicating limited or very little confidence in the effect estimated, and the true effect is likely to be considerably different than predicted by best current estimates. Accordingly, the recommendations are conditional, and decisions should be made with the values and preferences of the individual patient in mind.

In patients with preserved liver function who are ineligible for LRT or resection, or who have metastatic disease, the authors suggest that first-line treatment should be the combination of atezolizumab and bevacizumab rather than sorafenib. Bevacizumab comes with a bleeding risk, so patients should first be evaluated endoscopically and treated for esophageal varices. For patients who are ineligible for bevacizumab, alternatives are lenvatinib or sorafenib. Patients who are more concerned about disease progression than adverse events may want to consider lenvatinib rather than sorafenib, while those concerned about blood pressure control and who are less concerned about adverse skin reactions may choose sorafenib.

Options for second-line therapy after sorafenib include cabozantinib (mortality reduction, 2.2 months) and pembrolizumab (mortality reduction, 3.3 months). Patients with alpha-fetoprotein levels higher than 400 ng/mL may be candidates for treatment with ramucirumab (mortality reduction, 1.2 months). Another option is regorafenib (mortality reduction, 2.8 months). Patients who are more concerned about adverse effects than a potential survival benefit with any of these therapies may reasonably choose no systemic therapy.

For HCC patients with poor liver function, who are not eligible for LRT or resection, or with metastatic disease, the guidelines recommend against routine use of sorafenib.

In the setting of adjuvant therapy following curative surgical resection, curative local ablation, or TACE LRT, the guidelines recommend against the use of sorafenib. The authors also recommended against the use of bevacizumab following TACE LRT.

The authors noted that there is no high-quality comparative evidence in the second-line setting for atezolizumab plus bevacizumab, sorafenib, or lenvatinib. There is a dearth of evidence and few biomarkers to guide personalization of therapies, which places the emphasis on patient preferences, risks, and benefits.

The authors disclosed no conflicts.

New recommendations from the American Gastroenterological Association focus on choice of systemic therapy in hepatocellular carcinoma (HCC) patients. The guideline authors point out that prognosis and treatment decisions are both heavily dependent on a combination of the severity of underlying disease and biological characteristics of the tumor.

The document includes options for patients who are ineligible for locoregional therapy or resection, patients with metastatic disease and preserved liver function, patients with poor liver function, and patients receiving adjuvant therapy following surgery or locoregional therapy (LRT).

Intermediate or advanced tumor stage is common among HCC patients, and curative options such as surgery and ablation are generally limited to early-stage disease. LRTs – including transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and systemic therapy – may be employed against advanced or metastatic HCC, according to the authors, led by Grace L. Su, MD, of the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor, and the Veterans Affairs Ann Arbor Healthcare System.

In 2007, the Food and Drug Administration approved the multikinase inhibitor sorafenib as the first systemic therapy for HCC. The new guideline comes in the wake of new systemic therapeutic options that have arrived in the years since, including molecularly targeted therapy and immunotherapy. The authors of the guidance, published in Gastroenterology, include advice on both first- and second-line therapies.

Certainty of evidence for the recommendations ranges from low to very low, indicating limited or very little confidence in the effect estimated, and the true effect is likely to be considerably different than predicted by best current estimates. Accordingly, the recommendations are conditional, and decisions should be made with the values and preferences of the individual patient in mind.

In patients with preserved liver function who are ineligible for LRT or resection, or who have metastatic disease, the authors suggest that first-line treatment should be the combination of atezolizumab and bevacizumab rather than sorafenib. Bevacizumab comes with a bleeding risk, so patients should first be evaluated endoscopically and treated for esophageal varices. For patients who are ineligible for bevacizumab, alternatives are lenvatinib or sorafenib. Patients who are more concerned about disease progression than adverse events may want to consider lenvatinib rather than sorafenib, while those concerned about blood pressure control and who are less concerned about adverse skin reactions may choose sorafenib.

Options for second-line therapy after sorafenib include cabozantinib (mortality reduction, 2.2 months) and pembrolizumab (mortality reduction, 3.3 months). Patients with alpha-fetoprotein levels higher than 400 ng/mL may be candidates for treatment with ramucirumab (mortality reduction, 1.2 months). Another option is regorafenib (mortality reduction, 2.8 months). Patients who are more concerned about adverse effects than a potential survival benefit with any of these therapies may reasonably choose no systemic therapy.

For HCC patients with poor liver function, who are not eligible for LRT or resection, or with metastatic disease, the guidelines recommend against routine use of sorafenib.

In the setting of adjuvant therapy following curative surgical resection, curative local ablation, or TACE LRT, the guidelines recommend against the use of sorafenib. The authors also recommended against the use of bevacizumab following TACE LRT.

The authors noted that there is no high-quality comparative evidence in the second-line setting for atezolizumab plus bevacizumab, sorafenib, or lenvatinib. There is a dearth of evidence and few biomarkers to guide personalization of therapies, which places the emphasis on patient preferences, risks, and benefits.

The authors disclosed no conflicts.