Conference Coverage

This transcript has been edited for clarity.

Michelle L. O’Donoghue, MD, MPH: Hi. This is Dr. Michelle O’Donoghue reporting for Medscape. Joining me today is Dr. Sahil Parikh, who’s a cardiologist and an interventionalist at Columbia University. He’s an associate professor of medicine.

We’ll be discussing two interesting trials that were presented at the ESC Congress here in Amsterdam. They do have the potential to be very practice-changing, so I think it’s worth talking about.
 

The FIRE trial

The first trial we’ll be talking about is the FIRE trial. Perhaps setting the stage, Sahil, I’d love to get your thoughts. We’ve had data in this space to suggest that, for patients with STEMI [ST-segment elevation myocardial infarction], a strategy of complete revascularization – and not only treating the culprit lesion but also treating additional lesions – may be of benefit. Where does that lead us in terms of what we didn’t know?

Sahil A. Parikh, MD: I think that the practice has moved, at least in the United States, over the past two decades, from staging percutaneous coronary interventions over 30 days from index to intervention to now trying to do patients in the same hospitalization whenever possible to achieve complete revascularization.

I think these data support not only that complete revascularization is compulsory now in these patients, but also doing it sooner rather than later, and that the benefit applies to most of the patients that we see in clinical practice. In the earlier data, the patients were relatively youthful – under Medicare age, less than 65 – and now this dataset has a median age of 80. This is more like the real-world clinical practice that most of us are encountering, and it extends the benefit, perhaps, greater than we’ve ever seen before.

O’Donoghue: The FIRE trial is interesting. As you say, it enrolled patients who were over the age of 75, where I think that some proceduralists are probably a little bit hesitant to think about complete revascularization due to concerns about any additional contrast load on their kidneys and other types of comorbidities. Of course, for any trial, there’s going to be some patient selection.

I think it’s very reassuring that even in this older patient group, a strategy of treating all the lesions – and not only in STEMI but also in non-STEMI patients – reduced cardiovascular events and mortality. I was really quite impressed by the mortality benefit.

Parikh: The mortality curve is almost surprising to me. On the other hand, it emboldens us now that we can treat these patients more completely and earlier in their clinical presentation. Certainly, we worried about contrast exposure and the duration of procedures in this older population, but it seems that the benefit that’s derived, which we saw in younger patients where we had a natural inclination to be more aggressive, extends also to this older population.
 

MULTISTARS AMI

O’Donoghue: To the question of timing, as you mentioned, prior to this, we had a study presented earlier this year, the BIOVASC trial, which also was suggestive that maybe earlier complete revascularization was better. But it wasn’t a significant difference, at least for the primary outcome. Now we have MULTISTARS AMI, which is very supportive of what we saw earlier this year, suggesting that complete revascularization really at the time that you’re treating the culprit may be the way to go.

Parikh: All of us, as interventionalists, are circumspect about what we might do in the middle of the night versus what we would do in the light of day. Certainly it seems clear, particularly if it’s straightforward anatomy, that taking care of it in the index procedure is not only saving contrast and fluoroscopy time, but it’s also providing a clinical benefit to the patients. That’s something that will also impact how clinicians interpret these data. Previously, there was always a question about whether we should just do it in the same hospitalization or do it at the same time. I think now, increasingly, we’re emboldened to do more in the index procedure.

O’Donoghue: When you’re thinking about nonculprit lesions and which ones to treat, do you always make that determination based on physiologic guidance of some kind? Are you using instantaneous wave-free ratio? What’s your practice?

Parikh: In the acute setting, imaging is superior for at least the assessment of which is a culprit. If you see a ruptured atherothrombotic situation on optical coherence tomography, for example, that’s fairly convincing and definitive. In the absence of that physiology, we are taught to avoid in the infarct-related artery because of potential spuriously false-negative findings.

In this situation, certainly, an imaging subgroup probably would be helpful because some of the benefit is almost certainly derived from identifying the infarct-related artery by accident – in other words, doing what you thought was the nonculprit artery, which is, in fact, the culprit. I think that probably is part of this. As somebody who uses imaging in the overwhelming number of my cases, I think that imaging would be an important surrogate to this.
 

Index procedure versus staged

O’Donoghue: For the operator who is coming in to do their STEMI case at 2:00 in the morning, would these data now push you toward doing complete revascularization at that time of night, or do you think that there is wiggle room in terms of interpreting these results regarding timing, where as long as you were doing it before hospital discharge and not, let’s say, 30 days out, that you may be able to derive the same benefit? What are some of the pros and cons?

Parikh: There’s definitely a fatigue factor in the middle of the night if it’s a particularly arduous intervention for the index infarct-related artery. I think there’s a human element where it may make sense just to stop and then bring the patient back in the same hospitalization. It’s clear, though, that doing complete revascularization is better and doing it sooner is better. How soon one actually does it is a judgment call, as ever.

In our practice, we’ve been pushing ourselves to get most of the patients done in their index hospitalization. If you have a left-sided culprit, the left anterior descending artery, for example, and there’s a high-grade stenosis in the circumflex, it may make sense to take care of that in the same index procedure. If, on the other hand, it’s in the right coronary artery where you have to put a new guide in and spend more time, that may be a patient whom you stage. I think those nuances will come up as interventionalists look at the subgroup analysis data more carefully.

O’Donoghue: Those are great points, and I think they also underscore that we always need to think about what type of patient was enrolled in these studies. Certainly, if you have somebody with renal dysfunction, there might be more concern about giving them a large contrast load all in one sitting, albeit hard to know whether they do or not. But spacing that out by just a couple of days would really have a big impact.

Parikh: Very often in the STEMI patient, you don’t have the benefit of knowing the creatinine. The patient will come in immediately, if not directly from the ambulance to the cath lab, and there are no laboratories at all to work with. If the patient has never been seen in the system before, you won’t know. Again, in those situations, one may have pause, particularly if it’s an older patient. I think what’s reassuring, though, is that the data are supportive of being more aggressive earlier, and certainly this is the dataset that we were looking for.

O’Donoghue: To summarize, the two key takeaways are that, one, we now have more data to support a complete revascularization strategy and even extending that now to non-STEMI patients. Two, sooner appears to be better, so ideally, all done at the time of the index procedure. I think this is very interesting science and we’ll see how it changes practice.

Thanks for joining me today. Signing off for Medscape, this is Dr. Michelle O’Donoghue.

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group.

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

This transcript has been edited for clarity.

Michelle L. O’Donoghue, MD, MPH: Hi. This is Dr. Michelle O’Donoghue reporting for Medscape. Joining me today is Dr. Sahil Parikh, who’s a cardiologist and an interventionalist at Columbia University. He’s an associate professor of medicine.

We’ll be discussing two interesting trials that were presented at the ESC Congress here in Amsterdam. They do have the potential to be very practice-changing, so I think it’s worth talking about.
 

The FIRE trial

The first trial we’ll be talking about is the FIRE trial. Perhaps setting the stage, Sahil, I’d love to get your thoughts. We’ve had data in this space to suggest that, for patients with STEMI [ST-segment elevation myocardial infarction], a strategy of complete revascularization – and not only treating the culprit lesion but also treating additional lesions – may be of benefit. Where does that lead us in terms of what we didn’t know?

Sahil A. Parikh, MD: I think that the practice has moved, at least in the United States, over the past two decades, from staging percutaneous coronary interventions over 30 days from index to intervention to now trying to do patients in the same hospitalization whenever possible to achieve complete revascularization.

I think these data support not only that complete revascularization is compulsory now in these patients, but also doing it sooner rather than later, and that the benefit applies to most of the patients that we see in clinical practice. In the earlier data, the patients were relatively youthful – under Medicare age, less than 65 – and now this dataset has a median age of 80. This is more like the real-world clinical practice that most of us are encountering, and it extends the benefit, perhaps, greater than we’ve ever seen before.

O’Donoghue: The FIRE trial is interesting. As you say, it enrolled patients who were over the age of 75, where I think that some proceduralists are probably a little bit hesitant to think about complete revascularization due to concerns about any additional contrast load on their kidneys and other types of comorbidities. Of course, for any trial, there’s going to be some patient selection.

I think it’s very reassuring that even in this older patient group, a strategy of treating all the lesions – and not only in STEMI but also in non-STEMI patients – reduced cardiovascular events and mortality. I was really quite impressed by the mortality benefit.

Parikh: The mortality curve is almost surprising to me. On the other hand, it emboldens us now that we can treat these patients more completely and earlier in their clinical presentation. Certainly, we worried about contrast exposure and the duration of procedures in this older population, but it seems that the benefit that’s derived, which we saw in younger patients where we had a natural inclination to be more aggressive, extends also to this older population.
 

MULTISTARS AMI

O’Donoghue: To the question of timing, as you mentioned, prior to this, we had a study presented earlier this year, the BIOVASC trial, which also was suggestive that maybe earlier complete revascularization was better. But it wasn’t a significant difference, at least for the primary outcome. Now we have MULTISTARS AMI, which is very supportive of what we saw earlier this year, suggesting that complete revascularization really at the time that you’re treating the culprit may be the way to go.

Parikh: All of us, as interventionalists, are circumspect about what we might do in the middle of the night versus what we would do in the light of day. Certainly it seems clear, particularly if it’s straightforward anatomy, that taking care of it in the index procedure is not only saving contrast and fluoroscopy time, but it’s also providing a clinical benefit to the patients. That’s something that will also impact how clinicians interpret these data. Previously, there was always a question about whether we should just do it in the same hospitalization or do it at the same time. I think now, increasingly, we’re emboldened to do more in the index procedure.

O’Donoghue: When you’re thinking about nonculprit lesions and which ones to treat, do you always make that determination based on physiologic guidance of some kind? Are you using instantaneous wave-free ratio? What’s your practice?

Parikh: In the acute setting, imaging is superior for at least the assessment of which is a culprit. If you see a ruptured atherothrombotic situation on optical coherence tomography, for example, that’s fairly convincing and definitive. In the absence of that physiology, we are taught to avoid in the infarct-related artery because of potential spuriously false-negative findings.

In this situation, certainly, an imaging subgroup probably would be helpful because some of the benefit is almost certainly derived from identifying the infarct-related artery by accident – in other words, doing what you thought was the nonculprit artery, which is, in fact, the culprit. I think that probably is part of this. As somebody who uses imaging in the overwhelming number of my cases, I think that imaging would be an important surrogate to this.
 

Index procedure versus staged

O’Donoghue: For the operator who is coming in to do their STEMI case at 2:00 in the morning, would these data now push you toward doing complete revascularization at that time of night, or do you think that there is wiggle room in terms of interpreting these results regarding timing, where as long as you were doing it before hospital discharge and not, let’s say, 30 days out, that you may be able to derive the same benefit? What are some of the pros and cons?

Parikh: There’s definitely a fatigue factor in the middle of the night if it’s a particularly arduous intervention for the index infarct-related artery. I think there’s a human element where it may make sense just to stop and then bring the patient back in the same hospitalization. It’s clear, though, that doing complete revascularization is better and doing it sooner is better. How soon one actually does it is a judgment call, as ever.

In our practice, we’ve been pushing ourselves to get most of the patients done in their index hospitalization. If you have a left-sided culprit, the left anterior descending artery, for example, and there’s a high-grade stenosis in the circumflex, it may make sense to take care of that in the same index procedure. If, on the other hand, it’s in the right coronary artery where you have to put a new guide in and spend more time, that may be a patient whom you stage. I think those nuances will come up as interventionalists look at the subgroup analysis data more carefully.

O’Donoghue: Those are great points, and I think they also underscore that we always need to think about what type of patient was enrolled in these studies. Certainly, if you have somebody with renal dysfunction, there might be more concern about giving them a large contrast load all in one sitting, albeit hard to know whether they do or not. But spacing that out by just a couple of days would really have a big impact.

Parikh: Very often in the STEMI patient, you don’t have the benefit of knowing the creatinine. The patient will come in immediately, if not directly from the ambulance to the cath lab, and there are no laboratories at all to work with. If the patient has never been seen in the system before, you won’t know. Again, in those situations, one may have pause, particularly if it’s an older patient. I think what’s reassuring, though, is that the data are supportive of being more aggressive earlier, and certainly this is the dataset that we were looking for.

O’Donoghue: To summarize, the two key takeaways are that, one, we now have more data to support a complete revascularization strategy and even extending that now to non-STEMI patients. Two, sooner appears to be better, so ideally, all done at the time of the index procedure. I think this is very interesting science and we’ll see how it changes practice.

Thanks for joining me today. Signing off for Medscape, this is Dr. Michelle O’Donoghue.

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group.

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

This transcript has been edited for clarity.

Michelle L. O’Donoghue, MD, MPH: Hi. This is Dr. Michelle O’Donoghue reporting for Medscape. Joining me today is Dr. Sahil Parikh, who’s a cardiologist and an interventionalist at Columbia University. He’s an associate professor of medicine.

We’ll be discussing two interesting trials that were presented at the ESC Congress here in Amsterdam. They do have the potential to be very practice-changing, so I think it’s worth talking about.
 

The FIRE trial

The first trial we’ll be talking about is the FIRE trial. Perhaps setting the stage, Sahil, I’d love to get your thoughts. We’ve had data in this space to suggest that, for patients with STEMI [ST-segment elevation myocardial infarction], a strategy of complete revascularization – and not only treating the culprit lesion but also treating additional lesions – may be of benefit. Where does that lead us in terms of what we didn’t know?

Sahil A. Parikh, MD: I think that the practice has moved, at least in the United States, over the past two decades, from staging percutaneous coronary interventions over 30 days from index to intervention to now trying to do patients in the same hospitalization whenever possible to achieve complete revascularization.

I think these data support not only that complete revascularization is compulsory now in these patients, but also doing it sooner rather than later, and that the benefit applies to most of the patients that we see in clinical practice. In the earlier data, the patients were relatively youthful – under Medicare age, less than 65 – and now this dataset has a median age of 80. This is more like the real-world clinical practice that most of us are encountering, and it extends the benefit, perhaps, greater than we’ve ever seen before.

O’Donoghue: The FIRE trial is interesting. As you say, it enrolled patients who were over the age of 75, where I think that some proceduralists are probably a little bit hesitant to think about complete revascularization due to concerns about any additional contrast load on their kidneys and other types of comorbidities. Of course, for any trial, there’s going to be some patient selection.

I think it’s very reassuring that even in this older patient group, a strategy of treating all the lesions – and not only in STEMI but also in non-STEMI patients – reduced cardiovascular events and mortality. I was really quite impressed by the mortality benefit.

Parikh: The mortality curve is almost surprising to me. On the other hand, it emboldens us now that we can treat these patients more completely and earlier in their clinical presentation. Certainly, we worried about contrast exposure and the duration of procedures in this older population, but it seems that the benefit that’s derived, which we saw in younger patients where we had a natural inclination to be more aggressive, extends also to this older population.
 

MULTISTARS AMI

O’Donoghue: To the question of timing, as you mentioned, prior to this, we had a study presented earlier this year, the BIOVASC trial, which also was suggestive that maybe earlier complete revascularization was better. But it wasn’t a significant difference, at least for the primary outcome. Now we have MULTISTARS AMI, which is very supportive of what we saw earlier this year, suggesting that complete revascularization really at the time that you’re treating the culprit may be the way to go.

Parikh: All of us, as interventionalists, are circumspect about what we might do in the middle of the night versus what we would do in the light of day. Certainly it seems clear, particularly if it’s straightforward anatomy, that taking care of it in the index procedure is not only saving contrast and fluoroscopy time, but it’s also providing a clinical benefit to the patients. That’s something that will also impact how clinicians interpret these data. Previously, there was always a question about whether we should just do it in the same hospitalization or do it at the same time. I think now, increasingly, we’re emboldened to do more in the index procedure.

O’Donoghue: When you’re thinking about nonculprit lesions and which ones to treat, do you always make that determination based on physiologic guidance of some kind? Are you using instantaneous wave-free ratio? What’s your practice?

Parikh: In the acute setting, imaging is superior for at least the assessment of which is a culprit. If you see a ruptured atherothrombotic situation on optical coherence tomography, for example, that’s fairly convincing and definitive. In the absence of that physiology, we are taught to avoid in the infarct-related artery because of potential spuriously false-negative findings.

In this situation, certainly, an imaging subgroup probably would be helpful because some of the benefit is almost certainly derived from identifying the infarct-related artery by accident – in other words, doing what you thought was the nonculprit artery, which is, in fact, the culprit. I think that probably is part of this. As somebody who uses imaging in the overwhelming number of my cases, I think that imaging would be an important surrogate to this.
 

Index procedure versus staged

O’Donoghue: For the operator who is coming in to do their STEMI case at 2:00 in the morning, would these data now push you toward doing complete revascularization at that time of night, or do you think that there is wiggle room in terms of interpreting these results regarding timing, where as long as you were doing it before hospital discharge and not, let’s say, 30 days out, that you may be able to derive the same benefit? What are some of the pros and cons?

Parikh: There’s definitely a fatigue factor in the middle of the night if it’s a particularly arduous intervention for the index infarct-related artery. I think there’s a human element where it may make sense just to stop and then bring the patient back in the same hospitalization. It’s clear, though, that doing complete revascularization is better and doing it sooner is better. How soon one actually does it is a judgment call, as ever.

In our practice, we’ve been pushing ourselves to get most of the patients done in their index hospitalization. If you have a left-sided culprit, the left anterior descending artery, for example, and there’s a high-grade stenosis in the circumflex, it may make sense to take care of that in the same index procedure. If, on the other hand, it’s in the right coronary artery where you have to put a new guide in and spend more time, that may be a patient whom you stage. I think those nuances will come up as interventionalists look at the subgroup analysis data more carefully.

O’Donoghue: Those are great points, and I think they also underscore that we always need to think about what type of patient was enrolled in these studies. Certainly, if you have somebody with renal dysfunction, there might be more concern about giving them a large contrast load all in one sitting, albeit hard to know whether they do or not. But spacing that out by just a couple of days would really have a big impact.

Parikh: Very often in the STEMI patient, you don’t have the benefit of knowing the creatinine. The patient will come in immediately, if not directly from the ambulance to the cath lab, and there are no laboratories at all to work with. If the patient has never been seen in the system before, you won’t know. Again, in those situations, one may have pause, particularly if it’s an older patient. I think what’s reassuring, though, is that the data are supportive of being more aggressive earlier, and certainly this is the dataset that we were looking for.

O’Donoghue: To summarize, the two key takeaways are that, one, we now have more data to support a complete revascularization strategy and even extending that now to non-STEMI patients. Two, sooner appears to be better, so ideally, all done at the time of the index procedure. I think this is very interesting science and we’ll see how it changes practice.

Thanks for joining me today. Signing off for Medscape, this is Dr. Michelle O’Donoghue.

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group.

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

Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”

“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.

“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
 

Understanding the multifaceted nature of chronic cough

Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.

Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.

Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
 

Effective management strategies

Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.

The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.

“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.

Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
 

Current treatments and future prospects

Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.

Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.

Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.

“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.

Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.

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

Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”

“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.

“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
 

Understanding the multifaceted nature of chronic cough

Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.

Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.

Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
 

Effective management strategies

Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.

The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.

“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.

Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
 

Current treatments and future prospects

Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.

Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.

Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.

“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.

Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.

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

Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”

“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.

“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
 

Understanding the multifaceted nature of chronic cough

Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.

Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.

Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
 

Effective management strategies

Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.

The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.

“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.

Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
 

Current treatments and future prospects

Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.

Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.

Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.

“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.

Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.

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

Should patients with acute myeloid leukemia (AML) for whom induction therapy fails to induce complete remission proceed to allogeneic hematopoietic stem cell transplant anyway? Or do these patients fare better when they receive an intensive salvage induction regimen to bring them into remission before transplant?

This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.

Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.

“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”

According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.

If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.

The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.

In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.

Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.

At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.

Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.

The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.

These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.

A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.

Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
 

Counterpoint: Aim for complete remission

Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.

The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.

“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.

Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.

A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.

Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.

Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.

It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.

One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.

However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.

“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.

The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Should patients with acute myeloid leukemia (AML) for whom induction therapy fails to induce complete remission proceed to allogeneic hematopoietic stem cell transplant anyway? Or do these patients fare better when they receive an intensive salvage induction regimen to bring them into remission before transplant?

This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.

Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.

“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”

According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.

If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.

The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.

In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.

Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.

At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.

Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.

The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.

These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.

A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.

Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
 

Counterpoint: Aim for complete remission

Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.

The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.

“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.

Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.

A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.

Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.

Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.

It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.

One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.

However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.

“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.

The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Should patients with acute myeloid leukemia (AML) for whom induction therapy fails to induce complete remission proceed to allogeneic hematopoietic stem cell transplant anyway? Or do these patients fare better when they receive an intensive salvage induction regimen to bring them into remission before transplant?

This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.

Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.

“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”

According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.

If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.

The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.

In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.

Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.

At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.

Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.

The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.

These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.

A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.

Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
 

Counterpoint: Aim for complete remission

Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.

The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.

“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.

Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.

A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.

Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.

Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.

It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.

One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.

However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.

“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.

The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Despite a growing list of Janus kinase (JAK) inhibitors, ruxolitinib remains the go-to for patients with symptomatic, higher risk myelofibrosis, according to Anthony M. Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta.

“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”

Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.

Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.

A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.

JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”

He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”

Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 10⁹/L.

“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”

One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.

Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.

Pacritinib is approved specifically for patients with platelet counts below 50 x 10⁹/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.

“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.

Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.

There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.

Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.

“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.

No disclosure information was reported.

Despite a growing list of Janus kinase (JAK) inhibitors, ruxolitinib remains the go-to for patients with symptomatic, higher risk myelofibrosis, according to Anthony M. Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta.

“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”

Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.

Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.

A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.

JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”

He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”

Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 10⁹/L.

“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”

One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.

Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.

Pacritinib is approved specifically for patients with platelet counts below 50 x 10⁹/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.

“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.

Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.

There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.

Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.

“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.

No disclosure information was reported.

Despite a growing list of Janus kinase (JAK) inhibitors, ruxolitinib remains the go-to for patients with symptomatic, higher risk myelofibrosis, according to Anthony M. Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta.

“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”

Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.

Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.

A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.

JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”

He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”

Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 10⁹/L.

“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”

One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.

Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.

Pacritinib is approved specifically for patients with platelet counts below 50 x 10⁹/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.

“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.

Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.

There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.

Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.

“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.

No disclosure information was reported.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

AMSTERDAM – For patients hospitalized for acute heart failure, initiating treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) before hospital discharge was safe, it appeared to improve diuresis and natriuresis while reducing the administered diuretic dose, and it meant quicker initiation of guideline-directed therapy in a controlled study of 238 patients.

Treatment with dapagliflozin was begun for people with heart failure on their first day of hospitalization for an acute episode. Such treatment “can be safely started to optimize a key medication,” Zachary Cox, PharmD, said at the annual congress of the European Society of Cardiology. It improved fluid removal, as evidenced in the “totality of diuretic measures,” it resulted in reduced doses of IV diuretics, and it shortened length of stay in the hospital.

In current U.S. practice, about 80% of people hospitalized with heart failure do not initially receive treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor during their hospital stay when they are not already taking an agent from the class, noted Dr. Cox, professor of pharmacy at Lipscomb University College of Pharmacy in Nashville, Tenn.

Physicians are often uncomfortable changing a patient’s medications on the first day of a hospitalization, he noted. “Our results should embolden physicians” to begin treatment with an SGLT2 inhibitor early during hospitalization and to then continue it chronically, Dr. Cox said in a press briefing.

“Despite the messaging [from guidelines], we still see hesitancy. We hope more evidence of safety will improve uptake.” The study’s “key message is to start guideline-directed medical therapy early,” prior to hospital discharge, Dr. Cox concluded.
 

“Some support” for SGLT2 inhibitors

The study results “provide some support for SGLT2 inhibitors facilitating decongestion and hospital discharge without observed safety issues,” said Stephen D. Wiviott, MD, designated discussant for the report and a cardiologist and professor at Harvard Medical School in Boston.

While initiation of an SGLT2 inhibitor during an acute heart failure hospitalization received endorsement as a top management priority in both the 2023 heart failure guidelines of the European Society of Cardiology and in 2022 U.S. guidelines, evidence of the safety and efficacy of this approach has been scanty, Dr. Wiviott noted.

Two prior studies addressed the issue. The SOLOIST-WHF trial tested the combined SGLT1 and SGLT2 inhibitor sotagliflozin (Inpefa, Lexicon) for patients recently hospitalized for heart failure, but only 142 of the 596 participants who were randomly assigned to receive sotagliflozin began receiving it at least a day before hospital discharge; for the remaining 454, treatment with sotagliflozin began on their discharge day, noted Dr. Wiviott.

In the EMPULSE trial, 530 people hospitalized for acute heart failure were randomly assigned to initially receive empagliflozin (Jardiance, Boehringer Ingelheim and Lilly) or placebo during hospitalization. The primary endpoint was largely driven by an improvement in the patient-reported outcome, as assessed on the basis of the Kansas City Cardiomyopathy Questionnaire Total Symptom Score, Dr. Wiviott added.

The DICTATE-AHF study included 238 adults who were within 24 hours of first presenting to any of six participating U.S. hospitals with hypervolemic acute heart failure. All patients underwent a standard treatment protocol with IV loop diuretics, and half received additional, open-label treatment with a daily 10-mg dose of dapagliflozin.

The average age of the patients was 65 years, 71% had type 2 diabetes (the study excluded people with type 1 diabetes), and about half had a left ventricular ejection fraction of 40% or less.
 

Similar weight loss with lower diuretics dose

The study’s primary outcome was a measure of diuretic efficiency, calculated as a person’s cumulative weight change divided by the cumulative dose of loop diuretics.

Both treatment arms experienced nearly identical weight loss, but for the people who received dapagliflozin, this occurred with a lower cumulative dose of diuretics. The diuretic efficiency with dapagliflozin produced comparable weight loss with a 35% lower amount of loop diuretic dose, a difference that fell just short of significance (P = .06).

However, treatment with dapagliflozin also significantly boosted 24-hour natriuresis and 24-hour diuresis, and it significantly shortened the time to stopping treatment with IV diuretics and to hospital discharge, Dr. Cox reported. Dapagliflozin initiation and ongoing treatment was also safe and well tolerated compared with usual care.

The fact that the primary endpoint fell short of significance was “largely related” to the study’s relatively small size, Dr. Wiviott suggested. He noted that the DAPA ACT HF-TIMI 68 study, which is a much larger and potentially more definitive study of the safety and efficacy of dapagliflozin in comparison with usual care for patients with acute heart failure, is in progress. The study includes about 2,400 patients.

The primary outcome is the combined rate of cardiovascular death or worsening heart failure during the 2 months following randomization. Results are expected in 2024.

DICTATE-AHF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Cox has received research funding from AstraZeneca and has been a consultant to Roche and Translational Catalyst. Dr. Wiviott has received research funding from AstraZeneca and from Merck and has been a consultant to Icon Clinical and Novo Nordisk.
 

A version of this article appeared on Medscape.com.

It’s important to have counselors available for people diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS), according to medical oncologist Lachelle D. Weeks, MD, PhD, a specialist in both conditions at the Dana Farber Cancer Institute, Boston.

The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.

CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.

CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.

A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.

With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.

Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.

Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.

The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.

“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.

High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.

The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.

“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.

“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.

The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.

It’s important to have counselors available for people diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS), according to medical oncologist Lachelle D. Weeks, MD, PhD, a specialist in both conditions at the Dana Farber Cancer Institute, Boston.

The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.

CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.

CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.

A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.

With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.

Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.

Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.

The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.

“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.

High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.

The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.

“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.

“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.

The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.

It’s important to have counselors available for people diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS), according to medical oncologist Lachelle D. Weeks, MD, PhD, a specialist in both conditions at the Dana Farber Cancer Institute, Boston.

The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.

CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.

CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.

A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.

With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.

Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.

Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.

The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.

“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.

High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.

The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.

“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.

“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.

The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.

To avoid cardiovascular disease, the American Heart Association (AHA) recommends performing at least 150 minutes of moderate-intensity aerobic activity every week, 75 minutes of intense aerobic activity every week, or a combination of both, preferably spread out throughout the week. But how knowledgeable are physicians when it comes to prescribing exercise, and how should patients be assessed so that appropriate physical activity can be recommended?

In a presentation titled, “Patient Evaluation and Exercise Prescription in Primary Prevention,” Thelma Sánchez Grillo, MD, a cardiologist at the Clínica Bíblica Hospital in San José, Costa Rica, explained the benefits and risks of exercise and gave recommendations for proper patient assessment before prescribing physical activity.

“Exercise has cardioprotective, emotional, antiarrhythmic, and antithrombotic benefits, and it reduces stress,” she explained.

She also noted that the risk regarding cardiopulmonary and musculoskeletal components must be evaluated, because exercise can itself trigger coronary events, and the last thing intended when prescribing exercise is to cause complications. “We must recommend exercise progressively. We can’t suggest a high-intensity regimen to a patient if they haven’t had any preconditioning where collateral circulation could be developed and lung and cardiac capacity could be improved.”

Dr. Sánchez went on to say that, according to the AHA, patients should be classified as follows: those who exercise and those who don’t, those with a history of cardiovascular, metabolic, or renal disease, and those with symptomatic and asymptomatic diseases, in order to consider the parameters when recommending exercise.

“If the patient has symptoms and is doing light physical activity, like walking, they can keep doing this exercise and don’t need further assessments. But if they have a symptomatic disease and are not exercising, they need to be evaluated after exercise has been prescribed, and not just clinically, either. Some sort of diagnostic method should be considered. Also, for patients who are physically active and who desire to increase the intensity of their exercise, the recommendation is to perform a detailed clinical examination and, if necessary, perform additional imaging studies.”

Warning signs

• Dizziness.
• Orthopnea.
• Abnormal heart rate.
• Edema in the lower extremities.
• Chest pain, especially when occurring with exercise.
• Intermittent claudication.
• Heart murmurs.
• Dyspnea.
• Reduced output.
• Fatigue.

Calibrating exercise parameters

The parameters of frequency (number of sessions per week), intensity (perceived exertion measured by heart rate reached), time, and type (aerobic exercise vs. strength training) should be considered when forming an appropriate prescription for exercise, explained Dr. Sánchez.

“The big problem is that most physicians don’t know how to prescribe it properly. And beyond knowing how, the important thing is that, when we’re with the patient during the consultation, we ought to be doing more than just establishing a routine. We need to be motivators and we need to be identifying obstacles and the patient’s interest in exercise, because it’s clear that incorporating physical activity into our daily lives helps improve the quality and length of life,” the specialist added.

The recommendations are straightforward: for individuals aged 18-64 years, 150 minutes of moderate-intensity activity per week, whether aerobic, strength training, or mixed, should be prescribed. “We need to encourage moving more and sitting less, and recommend comprehensive programs that include coordination, balance, and muscle strengthening. If a sedentary lifestyle is a risk factor, we need to encourage patients to start performing physical activity for 1-2 minutes every hour, because any exercise must be gradual and progressive to avoid complications,” she noted.
 

Evaluate, then recommend

The specialist emphasized the importance of making personalized prescriptions, exercising caution, and performing adequate assessments to know which exercise routine to recommend. “The patient should also be involved in their self-care and must have an adequate diet and hydration, and we need to remind them that they shouldn’t be exercising if they have an infection, due to the risk of myocarditis and sudden death,” she added.

Rafaelina Concepción, MD, cardiologist from the Dominican Republic and vice president of the Inter-American Society of Cardiology for Central America and the Caribbean, agreed with the importance of assessing risk and risk factors for patients who request an exercise routine. “For example, in patients with prediabetes, it has been shown that exercising can slow the progression to diabetes. The essential thing is to use stratification and know what kind of exercise to recommend, whether aerobic, strength training, or a combination of the two, to improve functional capacity without reaching the threshold heart rate while reducing the risk of other comorbidities like hypertension, obesity, and high lipids, and achieving lifestyle changes.”

Carlos Franco, MD, a cardiologist in El Salvador, emphasized that there is no such thing as zero risk when evaluating a patient. “Of course, there’s a difference between an athlete and someone who isn’t physically active, but we need to profile all patients correctly, evaluate risk factors in detail, not overlook subclinical cardiovascular disease, and check whether they need stress testing or additional imaging to assess cardiac functional capacity. Also, exercise must be prescribed gradually, and the patient’s nutritional status must be assessed.”

Dr. Franco ended by explaining that physicians must understand how to prescribe the basics of exercise and make small interventions of reasonable intensity, provide practical advice, and, to the extent possible, rely on specialists such as physiatrists, sports specialists, and physical therapists.

This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.

To avoid cardiovascular disease, the American Heart Association (AHA) recommends performing at least 150 minutes of moderate-intensity aerobic activity every week, 75 minutes of intense aerobic activity every week, or a combination of both, preferably spread out throughout the week. But how knowledgeable are physicians when it comes to prescribing exercise, and how should patients be assessed so that appropriate physical activity can be recommended?

In a presentation titled, “Patient Evaluation and Exercise Prescription in Primary Prevention,” Thelma Sánchez Grillo, MD, a cardiologist at the Clínica Bíblica Hospital in San José, Costa Rica, explained the benefits and risks of exercise and gave recommendations for proper patient assessment before prescribing physical activity.

“Exercise has cardioprotective, emotional, antiarrhythmic, and antithrombotic benefits, and it reduces stress,” she explained.

She also noted that the risk regarding cardiopulmonary and musculoskeletal components must be evaluated, because exercise can itself trigger coronary events, and the last thing intended when prescribing exercise is to cause complications. “We must recommend exercise progressively. We can’t suggest a high-intensity regimen to a patient if they haven’t had any preconditioning where collateral circulation could be developed and lung and cardiac capacity could be improved.”

Dr. Sánchez went on to say that, according to the AHA, patients should be classified as follows: those who exercise and those who don’t, those with a history of cardiovascular, metabolic, or renal disease, and those with symptomatic and asymptomatic diseases, in order to consider the parameters when recommending exercise.

“If the patient has symptoms and is doing light physical activity, like walking, they can keep doing this exercise and don’t need further assessments. But if they have a symptomatic disease and are not exercising, they need to be evaluated after exercise has been prescribed, and not just clinically, either. Some sort of diagnostic method should be considered. Also, for patients who are physically active and who desire to increase the intensity of their exercise, the recommendation is to perform a detailed clinical examination and, if necessary, perform additional imaging studies.”

Warning signs

• Dizziness.
• Orthopnea.
• Abnormal heart rate.
• Edema in the lower extremities.
• Chest pain, especially when occurring with exercise.
• Intermittent claudication.
• Heart murmurs.
• Dyspnea.
• Reduced output.
• Fatigue.

Calibrating exercise parameters

The parameters of frequency (number of sessions per week), intensity (perceived exertion measured by heart rate reached), time, and type (aerobic exercise vs. strength training) should be considered when forming an appropriate prescription for exercise, explained Dr. Sánchez.

“The big problem is that most physicians don’t know how to prescribe it properly. And beyond knowing how, the important thing is that, when we’re with the patient during the consultation, we ought to be doing more than just establishing a routine. We need to be motivators and we need to be identifying obstacles and the patient’s interest in exercise, because it’s clear that incorporating physical activity into our daily lives helps improve the quality and length of life,” the specialist added.

The recommendations are straightforward: for individuals aged 18-64 years, 150 minutes of moderate-intensity activity per week, whether aerobic, strength training, or mixed, should be prescribed. “We need to encourage moving more and sitting less, and recommend comprehensive programs that include coordination, balance, and muscle strengthening. If a sedentary lifestyle is a risk factor, we need to encourage patients to start performing physical activity for 1-2 minutes every hour, because any exercise must be gradual and progressive to avoid complications,” she noted.
 

Evaluate, then recommend

The specialist emphasized the importance of making personalized prescriptions, exercising caution, and performing adequate assessments to know which exercise routine to recommend. “The patient should also be involved in their self-care and must have an adequate diet and hydration, and we need to remind them that they shouldn’t be exercising if they have an infection, due to the risk of myocarditis and sudden death,” she added.

Rafaelina Concepción, MD, cardiologist from the Dominican Republic and vice president of the Inter-American Society of Cardiology for Central America and the Caribbean, agreed with the importance of assessing risk and risk factors for patients who request an exercise routine. “For example, in patients with prediabetes, it has been shown that exercising can slow the progression to diabetes. The essential thing is to use stratification and know what kind of exercise to recommend, whether aerobic, strength training, or a combination of the two, to improve functional capacity without reaching the threshold heart rate while reducing the risk of other comorbidities like hypertension, obesity, and high lipids, and achieving lifestyle changes.”

Carlos Franco, MD, a cardiologist in El Salvador, emphasized that there is no such thing as zero risk when evaluating a patient. “Of course, there’s a difference between an athlete and someone who isn’t physically active, but we need to profile all patients correctly, evaluate risk factors in detail, not overlook subclinical cardiovascular disease, and check whether they need stress testing or additional imaging to assess cardiac functional capacity. Also, exercise must be prescribed gradually, and the patient’s nutritional status must be assessed.”

Dr. Franco ended by explaining that physicians must understand how to prescribe the basics of exercise and make small interventions of reasonable intensity, provide practical advice, and, to the extent possible, rely on specialists such as physiatrists, sports specialists, and physical therapists.

This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.

To avoid cardiovascular disease, the American Heart Association (AHA) recommends performing at least 150 minutes of moderate-intensity aerobic activity every week, 75 minutes of intense aerobic activity every week, or a combination of both, preferably spread out throughout the week. But how knowledgeable are physicians when it comes to prescribing exercise, and how should patients be assessed so that appropriate physical activity can be recommended?

In a presentation titled, “Patient Evaluation and Exercise Prescription in Primary Prevention,” Thelma Sánchez Grillo, MD, a cardiologist at the Clínica Bíblica Hospital in San José, Costa Rica, explained the benefits and risks of exercise and gave recommendations for proper patient assessment before prescribing physical activity.

“Exercise has cardioprotective, emotional, antiarrhythmic, and antithrombotic benefits, and it reduces stress,” she explained.

She also noted that the risk regarding cardiopulmonary and musculoskeletal components must be evaluated, because exercise can itself trigger coronary events, and the last thing intended when prescribing exercise is to cause complications. “We must recommend exercise progressively. We can’t suggest a high-intensity regimen to a patient if they haven’t had any preconditioning where collateral circulation could be developed and lung and cardiac capacity could be improved.”

Dr. Sánchez went on to say that, according to the AHA, patients should be classified as follows: those who exercise and those who don’t, those with a history of cardiovascular, metabolic, or renal disease, and those with symptomatic and asymptomatic diseases, in order to consider the parameters when recommending exercise.

“If the patient has symptoms and is doing light physical activity, like walking, they can keep doing this exercise and don’t need further assessments. But if they have a symptomatic disease and are not exercising, they need to be evaluated after exercise has been prescribed, and not just clinically, either. Some sort of diagnostic method should be considered. Also, for patients who are physically active and who desire to increase the intensity of their exercise, the recommendation is to perform a detailed clinical examination and, if necessary, perform additional imaging studies.”

Warning signs

• Dizziness.
• Orthopnea.
• Abnormal heart rate.
• Edema in the lower extremities.
• Chest pain, especially when occurring with exercise.
• Intermittent claudication.
• Heart murmurs.
• Dyspnea.
• Reduced output.
• Fatigue.

Calibrating exercise parameters

The parameters of frequency (number of sessions per week), intensity (perceived exertion measured by heart rate reached), time, and type (aerobic exercise vs. strength training) should be considered when forming an appropriate prescription for exercise, explained Dr. Sánchez.

“The big problem is that most physicians don’t know how to prescribe it properly. And beyond knowing how, the important thing is that, when we’re with the patient during the consultation, we ought to be doing more than just establishing a routine. We need to be motivators and we need to be identifying obstacles and the patient’s interest in exercise, because it’s clear that incorporating physical activity into our daily lives helps improve the quality and length of life,” the specialist added.

The recommendations are straightforward: for individuals aged 18-64 years, 150 minutes of moderate-intensity activity per week, whether aerobic, strength training, or mixed, should be prescribed. “We need to encourage moving more and sitting less, and recommend comprehensive programs that include coordination, balance, and muscle strengthening. If a sedentary lifestyle is a risk factor, we need to encourage patients to start performing physical activity for 1-2 minutes every hour, because any exercise must be gradual and progressive to avoid complications,” she noted.
 

Evaluate, then recommend

The specialist emphasized the importance of making personalized prescriptions, exercising caution, and performing adequate assessments to know which exercise routine to recommend. “The patient should also be involved in their self-care and must have an adequate diet and hydration, and we need to remind them that they shouldn’t be exercising if they have an infection, due to the risk of myocarditis and sudden death,” she added.

Rafaelina Concepción, MD, cardiologist from the Dominican Republic and vice president of the Inter-American Society of Cardiology for Central America and the Caribbean, agreed with the importance of assessing risk and risk factors for patients who request an exercise routine. “For example, in patients with prediabetes, it has been shown that exercising can slow the progression to diabetes. The essential thing is to use stratification and know what kind of exercise to recommend, whether aerobic, strength training, or a combination of the two, to improve functional capacity without reaching the threshold heart rate while reducing the risk of other comorbidities like hypertension, obesity, and high lipids, and achieving lifestyle changes.”

Carlos Franco, MD, a cardiologist in El Salvador, emphasized that there is no such thing as zero risk when evaluating a patient. “Of course, there’s a difference between an athlete and someone who isn’t physically active, but we need to profile all patients correctly, evaluate risk factors in detail, not overlook subclinical cardiovascular disease, and check whether they need stress testing or additional imaging to assess cardiac functional capacity. Also, exercise must be prescribed gradually, and the patient’s nutritional status must be assessed.”

Dr. Franco ended by explaining that physicians must understand how to prescribe the basics of exercise and make small interventions of reasonable intensity, provide practical advice, and, to the extent possible, rely on specialists such as physiatrists, sports specialists, and physical therapists.

This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.

AMSTERDAM – At the Radical Health Festival Helsinki this past June, Gerhard Hindricks, MD, PhD, was challenged by a young man when he dared to look into the crystal ball. “In the middle of my presentation, a maybe 25-year-old man stood up and said, ‘Dr. Hindricks, in 10 years, we will no longer need you!’ ” Dr. Hindricks noted at the great debate event “Will Artificial Intelligence Replace Cardiologists?” held at the annual congress of the European Society of Cardiology. He subsequently had an interesting discussion with the man. In his opinion, the future role of the physician is “an unavoidable discussion for cardiovascular medicine.”

Dr. Hindricks, from the University of Leipzig (Germany), considered artificial intelligence in cardiology to be “potentially the most important topic of the congress” and suggested that “we have to be more open to introducing new technologies into our practice. I sometimes have the impression that we are neither quick nor open enough to introducing new technologies, to leaving the old and to letting the new, better technology be effective in our patients.”
 

Asset or threat?

AI is dramatically changing the field and the role of the physician – but it is not making cardiologists superfluous. In this respect, Dr. Hindricks; Folkert Asselbergs, MD, PhD, professor of cardiology at the Amsterdam Heart Center; and Harriette Van Spall, MD, associate professor of medicine at McMaster University in Hamilton, Ont., were unanimous: They agreed, although they assess the opportunities and risks posed by AI differently.

Dr. Asselbergs saw AI as less of a threat and more of an asset. In his opinion, a cardiology-specific speech model could be used to the advantage of both patient and physician. A medical chatbot could offer patients information and suggested readings, and it could create the patient’s self-reported medical history and medical summaries for laypersons.

For physicians, a medical chatbot could be beneficial in the creation of patient reports, the selection of relevant literature, the creation of automated laboratory orders, the review of clinical discharge reports, for consultations, and for processing the consultations, as well as for complying with guidelines.

Dr. Asselbergs considered AI’s primary advantage to be the time that it saves, which can then be used “for complex interventions, palliative care, and acute treatment.”

The advantages of AI, he said, include the following:

• Efficiency and scale of AI in data analysis
• Automation
• AI does not get tired and is not biased
• Proactive health care provision and early intervention
• Reduction in health care costs
• Remains up to date with the latest knowledge.

He sees the following disadvantages:

• Lack of human contact, empathy, and the physician-patient relationship
• Ethical implications and challenges
• The potential for AI to make incorrect diagnoses or to be influenced by bias in the training data.

Medical supervision needed

For Dr. Van Spall, AI is primarily a tool. A generative AI could create useful materials such as images, videos, text, sound, 3D models, virtual environments, notes for clinical visits, medical summaries, and answers to clinical queries. But “the use of AI can lead to misinformation and expose the patient to risk, and there are no laws regulating liability.”

Dr. Van Spall stressed that AI could greatly increase efficiency. For example, in echocardiography, chamber volumes and function can be quantified automatically. ECGs can be interpreted automatically. “Even the workload associated with reading off of screens can be reduced, compared with unsupported reading.” However, she maintained that the use of AI requires medical supervision. “AI cannot function without cardiologists,” since it has “enormous limitations.” Dr. Van Spall does not see “any way to close the gaps that cardiologists may leave in terms of knowledge, service, and communication.”

According to the American College of Cardiology, 26% of the 32,000 cardiologists in the United States are older than 61 years. “That is a net loss of 546 cardiologists per year. We must use AI to support cardiologists, not to replace them,” said Dr. Van Spall.
 

Cardiologists becoming supervisors?

Dr. Asselbergs saw AI as a means of creating more equality. “Nearly everyone now has a smartphone. Let’s take ultrasound via AI as an example. There are rural areas that have no access to health care. If nurses or dietitians there create an ultrasound based on AI and send pictures for medical analysis, it will really help people.”

Dr. Hindricks hypothesized that machine learning and AI will make a huge difference in the field of rare diseases. Rare diseases are massively underdiagnosed simply because they are so rare and it requires a lot of experience to recognize them. “Digital elements can significantly support this,” said Dr. Hindricks.

For Dr. Van Spall, AI could make care and treatment safer. There will be more digital tools and virtual models available during training too. “I believe that the cardiologist will continue to occupy an important role, in terms of communication and processes. I do not see this role disappearing,” she said. Efficiency and precision are so important. “To make good decisions, we also want to get in touch with the person we trust.”

For Dr. Asselbergs, the role of cardiologists will change to one of a supervisor. “More joint decision-making, more discussion with our patients: I think this is the direction we’re heading in.”

This article was translated from the Medscape German Edition.

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

AMSTERDAM – At the Radical Health Festival Helsinki this past June, Gerhard Hindricks, MD, PhD, was challenged by a young man when he dared to look into the crystal ball. “In the middle of my presentation, a maybe 25-year-old man stood up and said, ‘Dr. Hindricks, in 10 years, we will no longer need you!’ ” Dr. Hindricks noted at the great debate event “Will Artificial Intelligence Replace Cardiologists?” held at the annual congress of the European Society of Cardiology. He subsequently had an interesting discussion with the man. In his opinion, the future role of the physician is “an unavoidable discussion for cardiovascular medicine.”

Dr. Hindricks, from the University of Leipzig (Germany), considered artificial intelligence in cardiology to be “potentially the most important topic of the congress” and suggested that “we have to be more open to introducing new technologies into our practice. I sometimes have the impression that we are neither quick nor open enough to introducing new technologies, to leaving the old and to letting the new, better technology be effective in our patients.”
 

Asset or threat?

AI is dramatically changing the field and the role of the physician – but it is not making cardiologists superfluous. In this respect, Dr. Hindricks; Folkert Asselbergs, MD, PhD, professor of cardiology at the Amsterdam Heart Center; and Harriette Van Spall, MD, associate professor of medicine at McMaster University in Hamilton, Ont., were unanimous: They agreed, although they assess the opportunities and risks posed by AI differently.

Dr. Asselbergs saw AI as less of a threat and more of an asset. In his opinion, a cardiology-specific speech model could be used to the advantage of both patient and physician. A medical chatbot could offer patients information and suggested readings, and it could create the patient’s self-reported medical history and medical summaries for laypersons.

For physicians, a medical chatbot could be beneficial in the creation of patient reports, the selection of relevant literature, the creation of automated laboratory orders, the review of clinical discharge reports, for consultations, and for processing the consultations, as well as for complying with guidelines.

Dr. Asselbergs considered AI’s primary advantage to be the time that it saves, which can then be used “for complex interventions, palliative care, and acute treatment.”

The advantages of AI, he said, include the following:

• Efficiency and scale of AI in data analysis
• Automation
• AI does not get tired and is not biased
• Proactive health care provision and early intervention
• Reduction in health care costs
• Remains up to date with the latest knowledge.

He sees the following disadvantages:

• Lack of human contact, empathy, and the physician-patient relationship
• Ethical implications and challenges
• The potential for AI to make incorrect diagnoses or to be influenced by bias in the training data.

Medical supervision needed

For Dr. Van Spall, AI is primarily a tool. A generative AI could create useful materials such as images, videos, text, sound, 3D models, virtual environments, notes for clinical visits, medical summaries, and answers to clinical queries. But “the use of AI can lead to misinformation and expose the patient to risk, and there are no laws regulating liability.”

Dr. Van Spall stressed that AI could greatly increase efficiency. For example, in echocardiography, chamber volumes and function can be quantified automatically. ECGs can be interpreted automatically. “Even the workload associated with reading off of screens can be reduced, compared with unsupported reading.” However, she maintained that the use of AI requires medical supervision. “AI cannot function without cardiologists,” since it has “enormous limitations.” Dr. Van Spall does not see “any way to close the gaps that cardiologists may leave in terms of knowledge, service, and communication.”

According to the American College of Cardiology, 26% of the 32,000 cardiologists in the United States are older than 61 years. “That is a net loss of 546 cardiologists per year. We must use AI to support cardiologists, not to replace them,” said Dr. Van Spall.
 

Cardiologists becoming supervisors?

Dr. Asselbergs saw AI as a means of creating more equality. “Nearly everyone now has a smartphone. Let’s take ultrasound via AI as an example. There are rural areas that have no access to health care. If nurses or dietitians there create an ultrasound based on AI and send pictures for medical analysis, it will really help people.”

Dr. Hindricks hypothesized that machine learning and AI will make a huge difference in the field of rare diseases. Rare diseases are massively underdiagnosed simply because they are so rare and it requires a lot of experience to recognize them. “Digital elements can significantly support this,” said Dr. Hindricks.

For Dr. Van Spall, AI could make care and treatment safer. There will be more digital tools and virtual models available during training too. “I believe that the cardiologist will continue to occupy an important role, in terms of communication and processes. I do not see this role disappearing,” she said. Efficiency and precision are so important. “To make good decisions, we also want to get in touch with the person we trust.”

For Dr. Asselbergs, the role of cardiologists will change to one of a supervisor. “More joint decision-making, more discussion with our patients: I think this is the direction we’re heading in.”

This article was translated from the Medscape German Edition.

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

AMSTERDAM – At the Radical Health Festival Helsinki this past June, Gerhard Hindricks, MD, PhD, was challenged by a young man when he dared to look into the crystal ball. “In the middle of my presentation, a maybe 25-year-old man stood up and said, ‘Dr. Hindricks, in 10 years, we will no longer need you!’ ” Dr. Hindricks noted at the great debate event “Will Artificial Intelligence Replace Cardiologists?” held at the annual congress of the European Society of Cardiology. He subsequently had an interesting discussion with the man. In his opinion, the future role of the physician is “an unavoidable discussion for cardiovascular medicine.”

Dr. Hindricks, from the University of Leipzig (Germany), considered artificial intelligence in cardiology to be “potentially the most important topic of the congress” and suggested that “we have to be more open to introducing new technologies into our practice. I sometimes have the impression that we are neither quick nor open enough to introducing new technologies, to leaving the old and to letting the new, better technology be effective in our patients.”
 

Asset or threat?

AI is dramatically changing the field and the role of the physician – but it is not making cardiologists superfluous. In this respect, Dr. Hindricks; Folkert Asselbergs, MD, PhD, professor of cardiology at the Amsterdam Heart Center; and Harriette Van Spall, MD, associate professor of medicine at McMaster University in Hamilton, Ont., were unanimous: They agreed, although they assess the opportunities and risks posed by AI differently.

Dr. Asselbergs saw AI as less of a threat and more of an asset. In his opinion, a cardiology-specific speech model could be used to the advantage of both patient and physician. A medical chatbot could offer patients information and suggested readings, and it could create the patient’s self-reported medical history and medical summaries for laypersons.

For physicians, a medical chatbot could be beneficial in the creation of patient reports, the selection of relevant literature, the creation of automated laboratory orders, the review of clinical discharge reports, for consultations, and for processing the consultations, as well as for complying with guidelines.

Dr. Asselbergs considered AI’s primary advantage to be the time that it saves, which can then be used “for complex interventions, palliative care, and acute treatment.”

The advantages of AI, he said, include the following:

• Efficiency and scale of AI in data analysis
• Automation
• AI does not get tired and is not biased
• Proactive health care provision and early intervention
• Reduction in health care costs
• Remains up to date with the latest knowledge.

He sees the following disadvantages:

• Lack of human contact, empathy, and the physician-patient relationship
• Ethical implications and challenges
• The potential for AI to make incorrect diagnoses or to be influenced by bias in the training data.

Medical supervision needed

For Dr. Van Spall, AI is primarily a tool. A generative AI could create useful materials such as images, videos, text, sound, 3D models, virtual environments, notes for clinical visits, medical summaries, and answers to clinical queries. But “the use of AI can lead to misinformation and expose the patient to risk, and there are no laws regulating liability.”

Dr. Van Spall stressed that AI could greatly increase efficiency. For example, in echocardiography, chamber volumes and function can be quantified automatically. ECGs can be interpreted automatically. “Even the workload associated with reading off of screens can be reduced, compared with unsupported reading.” However, she maintained that the use of AI requires medical supervision. “AI cannot function without cardiologists,” since it has “enormous limitations.” Dr. Van Spall does not see “any way to close the gaps that cardiologists may leave in terms of knowledge, service, and communication.”

According to the American College of Cardiology, 26% of the 32,000 cardiologists in the United States are older than 61 years. “That is a net loss of 546 cardiologists per year. We must use AI to support cardiologists, not to replace them,” said Dr. Van Spall.
 

Cardiologists becoming supervisors?

Dr. Asselbergs saw AI as a means of creating more equality. “Nearly everyone now has a smartphone. Let’s take ultrasound via AI as an example. There are rural areas that have no access to health care. If nurses or dietitians there create an ultrasound based on AI and send pictures for medical analysis, it will really help people.”

Dr. Hindricks hypothesized that machine learning and AI will make a huge difference in the field of rare diseases. Rare diseases are massively underdiagnosed simply because they are so rare and it requires a lot of experience to recognize them. “Digital elements can significantly support this,” said Dr. Hindricks.

For Dr. Van Spall, AI could make care and treatment safer. There will be more digital tools and virtual models available during training too. “I believe that the cardiologist will continue to occupy an important role, in terms of communication and processes. I do not see this role disappearing,” she said. Efficiency and precision are so important. “To make good decisions, we also want to get in touch with the person we trust.”

For Dr. Asselbergs, the role of cardiologists will change to one of a supervisor. “More joint decision-making, more discussion with our patients: I think this is the direction we’re heading in.”

This article was translated from the Medscape German Edition.

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

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

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

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

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

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

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

SAN DIEGO – Emerging research on so-called “clock genes” suggests that the human skin has different daytime and nighttime needs, according to Ava Shamban, MD.

“Paying attention to the circadian rhythm of the skin is every bit as important as moisturizing the skin,” Dr. Shamban, a dermatologist who practices in Santa Monica, Calif., said at the annual Masters of Aesthetics Symposium. “It is paramount to both your morning and evening skin regimen routine,” she added.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. “These natural processes respond primarily to light and dark and affect most living things, including animals, plants, and microbes,” she said. “The circadian system is composed of peripheral circadian oscillators in many other cells, including the skin.”

The science has been around awhile, but dermatologists didn’t understand its impact until recently, she said.

In 1729, the French astronomer Jean-Jacques d’Ortous de Mairan demonstrated that mimosa leaves, which open at dawn and close at dusk, continued this cycle even when kept in darkness. In the 1970s, Seymour Benzer and Ronald Konopka showed that mutations in an unknown gene disrupted the circadian clock of fruit flies.

And in 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for discovering molecular mechanisms that control circadian rhythm. Using fruit flies as a model, they isolated a gene that controls the normal daily biological rhythm.

“They showed that this gene encodes a protein that accumulates in the cell during the night and is then degraded during the day, and they identified additional protein components, exposing the mechanism governing the self-sustaining clockwork inside the cell,” said Dr. Shamban.

In humans and other mammals, the primary body clock is located in the suprachiasmatic nucleus, a cluster of approximately 10,000 neurons located on either side of the midline above the optic chiasma, about 3 cm behind the eyes. Several clock genes have been identified that regulate and control transcription and translation.

“Expression of these core clock genes inside the cell influences many signaling pathways, which allows the cells to identify the time of day and perform their appropriate function,” Dr. Shamban said. “Furthermore, phosphorylation of core clock proteins leads to degradation to keep the 24-hour cycle in sync.”

Photoreceptive molecules known as opsins also appear to play a role in regulating the skin’s clock. A systematic review of 22 articles published in 2020 found that opsins are present in keratinocytes, melanocytes, dermal fibroblasts, and hair follicle cells, and they have been shown to mediate wound healing, melanogenesis, hair growth, and skin photoaging in human and nonhuman species.

“You may wonder, why does the skin respond so nicely to light?” Dr. Shamban said. “Because it contains opsins, and light exposure through opsin-regulated pathways stimulates melanin production.”

Patients can support their skin’s clock genes by understanding that skin barrier functions such as photoprotection and sebum production are increased during the day, while skin permeability processes such as DNA repair, cell proliferation, and blood flow are enhanced at night.

“Your skin has different daytime and nighttime needs,” Dr. Shamban commented. “Simply put, daytime is defense, and nighttime is offense. I think we’ve known this intuitively, but to know that there is science supporting this idea is important.”

Dr. Shamban wrote the book “Heal Your Skin: The Breakthrough Plan for Renewal” (Wiley, 2011). She disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – Emerging research on so-called “clock genes” suggests that the human skin has different daytime and nighttime needs, according to Ava Shamban, MD.

“Paying attention to the circadian rhythm of the skin is every bit as important as moisturizing the skin,” Dr. Shamban, a dermatologist who practices in Santa Monica, Calif., said at the annual Masters of Aesthetics Symposium. “It is paramount to both your morning and evening skin regimen routine,” she added.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. “These natural processes respond primarily to light and dark and affect most living things, including animals, plants, and microbes,” she said. “The circadian system is composed of peripheral circadian oscillators in many other cells, including the skin.”

The science has been around awhile, but dermatologists didn’t understand its impact until recently, she said.

In 1729, the French astronomer Jean-Jacques d’Ortous de Mairan demonstrated that mimosa leaves, which open at dawn and close at dusk, continued this cycle even when kept in darkness. In the 1970s, Seymour Benzer and Ronald Konopka showed that mutations in an unknown gene disrupted the circadian clock of fruit flies.

And in 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for discovering molecular mechanisms that control circadian rhythm. Using fruit flies as a model, they isolated a gene that controls the normal daily biological rhythm.

“They showed that this gene encodes a protein that accumulates in the cell during the night and is then degraded during the day, and they identified additional protein components, exposing the mechanism governing the self-sustaining clockwork inside the cell,” said Dr. Shamban.

In humans and other mammals, the primary body clock is located in the suprachiasmatic nucleus, a cluster of approximately 10,000 neurons located on either side of the midline above the optic chiasma, about 3 cm behind the eyes. Several clock genes have been identified that regulate and control transcription and translation.

“Expression of these core clock genes inside the cell influences many signaling pathways, which allows the cells to identify the time of day and perform their appropriate function,” Dr. Shamban said. “Furthermore, phosphorylation of core clock proteins leads to degradation to keep the 24-hour cycle in sync.”

Photoreceptive molecules known as opsins also appear to play a role in regulating the skin’s clock. A systematic review of 22 articles published in 2020 found that opsins are present in keratinocytes, melanocytes, dermal fibroblasts, and hair follicle cells, and they have been shown to mediate wound healing, melanogenesis, hair growth, and skin photoaging in human and nonhuman species.

“You may wonder, why does the skin respond so nicely to light?” Dr. Shamban said. “Because it contains opsins, and light exposure through opsin-regulated pathways stimulates melanin production.”

Patients can support their skin’s clock genes by understanding that skin barrier functions such as photoprotection and sebum production are increased during the day, while skin permeability processes such as DNA repair, cell proliferation, and blood flow are enhanced at night.

“Your skin has different daytime and nighttime needs,” Dr. Shamban commented. “Simply put, daytime is defense, and nighttime is offense. I think we’ve known this intuitively, but to know that there is science supporting this idea is important.”

Dr. Shamban wrote the book “Heal Your Skin: The Breakthrough Plan for Renewal” (Wiley, 2011). She disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – Emerging research on so-called “clock genes” suggests that the human skin has different daytime and nighttime needs, according to Ava Shamban, MD.

“Paying attention to the circadian rhythm of the skin is every bit as important as moisturizing the skin,” Dr. Shamban, a dermatologist who practices in Santa Monica, Calif., said at the annual Masters of Aesthetics Symposium. “It is paramount to both your morning and evening skin regimen routine,” she added.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. “These natural processes respond primarily to light and dark and affect most living things, including animals, plants, and microbes,” she said. “The circadian system is composed of peripheral circadian oscillators in many other cells, including the skin.”

The science has been around awhile, but dermatologists didn’t understand its impact until recently, she said.

In 1729, the French astronomer Jean-Jacques d’Ortous de Mairan demonstrated that mimosa leaves, which open at dawn and close at dusk, continued this cycle even when kept in darkness. In the 1970s, Seymour Benzer and Ronald Konopka showed that mutations in an unknown gene disrupted the circadian clock of fruit flies.

And in 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for discovering molecular mechanisms that control circadian rhythm. Using fruit flies as a model, they isolated a gene that controls the normal daily biological rhythm.

“They showed that this gene encodes a protein that accumulates in the cell during the night and is then degraded during the day, and they identified additional protein components, exposing the mechanism governing the self-sustaining clockwork inside the cell,” said Dr. Shamban.

In humans and other mammals, the primary body clock is located in the suprachiasmatic nucleus, a cluster of approximately 10,000 neurons located on either side of the midline above the optic chiasma, about 3 cm behind the eyes. Several clock genes have been identified that regulate and control transcription and translation.

“Expression of these core clock genes inside the cell influences many signaling pathways, which allows the cells to identify the time of day and perform their appropriate function,” Dr. Shamban said. “Furthermore, phosphorylation of core clock proteins leads to degradation to keep the 24-hour cycle in sync.”

Photoreceptive molecules known as opsins also appear to play a role in regulating the skin’s clock. A systematic review of 22 articles published in 2020 found that opsins are present in keratinocytes, melanocytes, dermal fibroblasts, and hair follicle cells, and they have been shown to mediate wound healing, melanogenesis, hair growth, and skin photoaging in human and nonhuman species.

“You may wonder, why does the skin respond so nicely to light?” Dr. Shamban said. “Because it contains opsins, and light exposure through opsin-regulated pathways stimulates melanin production.”

Patients can support their skin’s clock genes by understanding that skin barrier functions such as photoprotection and sebum production are increased during the day, while skin permeability processes such as DNA repair, cell proliferation, and blood flow are enhanced at night.

“Your skin has different daytime and nighttime needs,” Dr. Shamban commented. “Simply put, daytime is defense, and nighttime is offense. I think we’ve known this intuitively, but to know that there is science supporting this idea is important.”

Dr. Shamban wrote the book “Heal Your Skin: The Breakthrough Plan for Renewal” (Wiley, 2011). She disclosed that she conducts clinical trials for many pharmaceutical and device companies.