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When viruses collide: Flu season during pandemic
The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.
Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.
“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”
With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.
Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”
That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.
Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
Flu vaccine ‘extra important’
The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.
The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.
But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
Risks of coinfection
About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.
“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”
Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
Distinguishing COVID-19 from flu
Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.
Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.
“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.
But even after that, symptoms can be difficult to distinguish.
“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”
But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”
Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.
Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.
In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”
Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”
The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”
That may be somewhat welcome as flu season arrives.
The physicians interviewed have no relevant disclosures.
The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.
Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.
“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”
With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.
Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”
That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.
Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
Flu vaccine ‘extra important’
The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.
The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.
But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
Risks of coinfection
About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.
“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”
Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
Distinguishing COVID-19 from flu
Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.
Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.
“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.
But even after that, symptoms can be difficult to distinguish.
“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”
But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”
Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.
Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.
In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”
Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”
The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”
That may be somewhat welcome as flu season arrives.
The physicians interviewed have no relevant disclosures.
The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.
Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.
“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”
With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.
Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”
That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.
Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
Flu vaccine ‘extra important’
The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.
The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.
But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
Risks of coinfection
About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.
“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”
Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
Distinguishing COVID-19 from flu
Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.
Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.
“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.
But even after that, symptoms can be difficult to distinguish.
“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”
But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”
Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.
Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.
In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”
Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”
The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”
That may be somewhat welcome as flu season arrives.
The physicians interviewed have no relevant disclosures.
Machine learning shows ability to predict diastolic dysfunction with ECG
A machine-learning model that uses readily available clinical and electrocardiography data may have the potential to identify left ventricular (LV) diastolic dysfunction, a key biomarker in predicting heart failure, without echocardiography, but a workable clinical platform is still far off, a team of North American researchers reported.
“This cost-effective strategy may be a valuable first clinical step for assessing the presence of LV dysfunction and may potentially aid in the early diagnosis and management of heart failure patients,” Nobuyuki Kagiyama, MD, PhD, of West Virginia University, Morgantown, and colleagues, wrote in the Journal of the American Academy of Cardiology.
The researchers reported on a multicenter, prospective study that evaluated 1,202 patients from three centers in the United States and one in Canada. To develop machine-learning models, the study pooled 814 patients from the U.S. institutions as an internal cohort. They were then randomly divided into a training set and an internal test set on an 80:20 basis (651 and 163). The 388 Canadian patients were reserved as an external set to test the model.
All patients had 12-lead ECG and simultaneous body surface signal-processed ECG (spECG) along with comprehensive two-dimensional Doppler ECG on the same day.
How the model works
The machine-learning model estimated echocardiographic LV relaxation velocities (e’) values using traditional ECG and spECG features. The model also took into account 10 basic clinical features: age; sex; systolic and diastolic blood pressure; and comorbid conditions such as cerebrovascular and cardiovascular disease, diabetes, hypertension, dyslipidemia, and chronic kidney disease.
Patient characteristics were starkly different between the internal (United States) and external (Canadian) cohorts, with the latter being 10 years older on average (65 vs. 44; P < .001), predominantly male (58.2% vs. 47.3%; P < .001) and with significantly lower rates of coronary artery disease (1.8% vs. 21.1%; P < .001), although average blood pressure was similar between the two groups.
The study used area under the curve (AUC) to calculate the predictability of the machine-learning estimated e’ values versus the guideline-based reduced e’, finding close correlation between the internal (AUC, 0.83; sensitivity, 78%; specificity, 77%; negative predictive value, 73%; and positive predictive value, 82%) and external test sets (AUC, 0.84; sensitivity, 90%; specificity, 61%; NPV, 81%; and PPV, 77%).
Similar variations between the two cohorts were reported for global LV diastolic dysfunction and reduced LV ejection fraction.
The final model used 18 features in all, including 3 clinical features (age, dyslipidemia, and hypertension), 7 scores from spECG features, and 8 from traditional ECG features.
Interpreting the results
Dr. Kagiyama and colleagues noted that, because impaired myocardial relaxation is an early sign of cardiac tissue deterioration, screening for it can aid in early detection of subclinical LVDD and earlier treatment for hypertension and diabetes. But they acknowledged that further studies are needed.
In an invited editorial, Khurram Nasir, MD, MPH, MSc, of Houston Methodist DeBakey Heart and Vascular Center and Rohan Khera, MD, MS, of Yale University, New Haven, Conn., wrote that the machine-learning model has a way to go.
They noted that the 73%-77% accuracy of the model in identifying diastolic dysfunction impedes its imminent use. “Although we are excited about the prospects of such developments, we hold out for better evidence for their actual use,” they wrote, adding that the algorithms have limited use in the clinic because most patients already get “definitive testing” if they need it.
Developing a machine-learning model that obviates the need for ECG for evaluating LV diastolic dysfunction seems dubious at this time, said Luigi Di Biase, MD, PhD, section head of electrophysiology and director of arrhythmia services at Montefiore Medical Center and professor at Albert Einstein College of Medicine, both in New York. “The echo is not a difficult test. It’s the most proven usable tool that we have in cardiology because it’s easy to reproduce, low cost, and noninvasive – so we have all that we want in medicine.”
But machine learning does have potential, added Dr. Di Biase, who’s also a member of the American College of Cardiology’s Electrophysiology Section Leadership Council. “If this application could predict the people that would develop diastolic dysfunction that leads to heart failure – because an echo at that time may be negative but there may be other features that tell me this patient will develop disease – then it would have a much different clinical impact.”
The National Science Foundation provided funding for the study. Heart Test Laboratories, doing business as Heart Sciences, provided funding and spECG devices. Dr. Kagiyama reported receiving a research grant from Hitachi Healthcare. A coauthor disclosed financial relationships with Heart Sciences, Ultronics, and Kencor Health.
Dr. Nasir, Dr. Khera, and Dr. Di Biase have no relevant financial relationships to disclose.
SOURCE: Kagiyama N et al. J Am Coll Cardiol. 2020;76:930-41.
A machine-learning model that uses readily available clinical and electrocardiography data may have the potential to identify left ventricular (LV) diastolic dysfunction, a key biomarker in predicting heart failure, without echocardiography, but a workable clinical platform is still far off, a team of North American researchers reported.
“This cost-effective strategy may be a valuable first clinical step for assessing the presence of LV dysfunction and may potentially aid in the early diagnosis and management of heart failure patients,” Nobuyuki Kagiyama, MD, PhD, of West Virginia University, Morgantown, and colleagues, wrote in the Journal of the American Academy of Cardiology.
The researchers reported on a multicenter, prospective study that evaluated 1,202 patients from three centers in the United States and one in Canada. To develop machine-learning models, the study pooled 814 patients from the U.S. institutions as an internal cohort. They were then randomly divided into a training set and an internal test set on an 80:20 basis (651 and 163). The 388 Canadian patients were reserved as an external set to test the model.
All patients had 12-lead ECG and simultaneous body surface signal-processed ECG (spECG) along with comprehensive two-dimensional Doppler ECG on the same day.
How the model works
The machine-learning model estimated echocardiographic LV relaxation velocities (e’) values using traditional ECG and spECG features. The model also took into account 10 basic clinical features: age; sex; systolic and diastolic blood pressure; and comorbid conditions such as cerebrovascular and cardiovascular disease, diabetes, hypertension, dyslipidemia, and chronic kidney disease.
Patient characteristics were starkly different between the internal (United States) and external (Canadian) cohorts, with the latter being 10 years older on average (65 vs. 44; P < .001), predominantly male (58.2% vs. 47.3%; P < .001) and with significantly lower rates of coronary artery disease (1.8% vs. 21.1%; P < .001), although average blood pressure was similar between the two groups.
The study used area under the curve (AUC) to calculate the predictability of the machine-learning estimated e’ values versus the guideline-based reduced e’, finding close correlation between the internal (AUC, 0.83; sensitivity, 78%; specificity, 77%; negative predictive value, 73%; and positive predictive value, 82%) and external test sets (AUC, 0.84; sensitivity, 90%; specificity, 61%; NPV, 81%; and PPV, 77%).
Similar variations between the two cohorts were reported for global LV diastolic dysfunction and reduced LV ejection fraction.
The final model used 18 features in all, including 3 clinical features (age, dyslipidemia, and hypertension), 7 scores from spECG features, and 8 from traditional ECG features.
Interpreting the results
Dr. Kagiyama and colleagues noted that, because impaired myocardial relaxation is an early sign of cardiac tissue deterioration, screening for it can aid in early detection of subclinical LVDD and earlier treatment for hypertension and diabetes. But they acknowledged that further studies are needed.
In an invited editorial, Khurram Nasir, MD, MPH, MSc, of Houston Methodist DeBakey Heart and Vascular Center and Rohan Khera, MD, MS, of Yale University, New Haven, Conn., wrote that the machine-learning model has a way to go.
They noted that the 73%-77% accuracy of the model in identifying diastolic dysfunction impedes its imminent use. “Although we are excited about the prospects of such developments, we hold out for better evidence for their actual use,” they wrote, adding that the algorithms have limited use in the clinic because most patients already get “definitive testing” if they need it.
Developing a machine-learning model that obviates the need for ECG for evaluating LV diastolic dysfunction seems dubious at this time, said Luigi Di Biase, MD, PhD, section head of electrophysiology and director of arrhythmia services at Montefiore Medical Center and professor at Albert Einstein College of Medicine, both in New York. “The echo is not a difficult test. It’s the most proven usable tool that we have in cardiology because it’s easy to reproduce, low cost, and noninvasive – so we have all that we want in medicine.”
But machine learning does have potential, added Dr. Di Biase, who’s also a member of the American College of Cardiology’s Electrophysiology Section Leadership Council. “If this application could predict the people that would develop diastolic dysfunction that leads to heart failure – because an echo at that time may be negative but there may be other features that tell me this patient will develop disease – then it would have a much different clinical impact.”
The National Science Foundation provided funding for the study. Heart Test Laboratories, doing business as Heart Sciences, provided funding and spECG devices. Dr. Kagiyama reported receiving a research grant from Hitachi Healthcare. A coauthor disclosed financial relationships with Heart Sciences, Ultronics, and Kencor Health.
Dr. Nasir, Dr. Khera, and Dr. Di Biase have no relevant financial relationships to disclose.
SOURCE: Kagiyama N et al. J Am Coll Cardiol. 2020;76:930-41.
A machine-learning model that uses readily available clinical and electrocardiography data may have the potential to identify left ventricular (LV) diastolic dysfunction, a key biomarker in predicting heart failure, without echocardiography, but a workable clinical platform is still far off, a team of North American researchers reported.
“This cost-effective strategy may be a valuable first clinical step for assessing the presence of LV dysfunction and may potentially aid in the early diagnosis and management of heart failure patients,” Nobuyuki Kagiyama, MD, PhD, of West Virginia University, Morgantown, and colleagues, wrote in the Journal of the American Academy of Cardiology.
The researchers reported on a multicenter, prospective study that evaluated 1,202 patients from three centers in the United States and one in Canada. To develop machine-learning models, the study pooled 814 patients from the U.S. institutions as an internal cohort. They were then randomly divided into a training set and an internal test set on an 80:20 basis (651 and 163). The 388 Canadian patients were reserved as an external set to test the model.
All patients had 12-lead ECG and simultaneous body surface signal-processed ECG (spECG) along with comprehensive two-dimensional Doppler ECG on the same day.
How the model works
The machine-learning model estimated echocardiographic LV relaxation velocities (e’) values using traditional ECG and spECG features. The model also took into account 10 basic clinical features: age; sex; systolic and diastolic blood pressure; and comorbid conditions such as cerebrovascular and cardiovascular disease, diabetes, hypertension, dyslipidemia, and chronic kidney disease.
Patient characteristics were starkly different between the internal (United States) and external (Canadian) cohorts, with the latter being 10 years older on average (65 vs. 44; P < .001), predominantly male (58.2% vs. 47.3%; P < .001) and with significantly lower rates of coronary artery disease (1.8% vs. 21.1%; P < .001), although average blood pressure was similar between the two groups.
The study used area under the curve (AUC) to calculate the predictability of the machine-learning estimated e’ values versus the guideline-based reduced e’, finding close correlation between the internal (AUC, 0.83; sensitivity, 78%; specificity, 77%; negative predictive value, 73%; and positive predictive value, 82%) and external test sets (AUC, 0.84; sensitivity, 90%; specificity, 61%; NPV, 81%; and PPV, 77%).
Similar variations between the two cohorts were reported for global LV diastolic dysfunction and reduced LV ejection fraction.
The final model used 18 features in all, including 3 clinical features (age, dyslipidemia, and hypertension), 7 scores from spECG features, and 8 from traditional ECG features.
Interpreting the results
Dr. Kagiyama and colleagues noted that, because impaired myocardial relaxation is an early sign of cardiac tissue deterioration, screening for it can aid in early detection of subclinical LVDD and earlier treatment for hypertension and diabetes. But they acknowledged that further studies are needed.
In an invited editorial, Khurram Nasir, MD, MPH, MSc, of Houston Methodist DeBakey Heart and Vascular Center and Rohan Khera, MD, MS, of Yale University, New Haven, Conn., wrote that the machine-learning model has a way to go.
They noted that the 73%-77% accuracy of the model in identifying diastolic dysfunction impedes its imminent use. “Although we are excited about the prospects of such developments, we hold out for better evidence for their actual use,” they wrote, adding that the algorithms have limited use in the clinic because most patients already get “definitive testing” if they need it.
Developing a machine-learning model that obviates the need for ECG for evaluating LV diastolic dysfunction seems dubious at this time, said Luigi Di Biase, MD, PhD, section head of electrophysiology and director of arrhythmia services at Montefiore Medical Center and professor at Albert Einstein College of Medicine, both in New York. “The echo is not a difficult test. It’s the most proven usable tool that we have in cardiology because it’s easy to reproduce, low cost, and noninvasive – so we have all that we want in medicine.”
But machine learning does have potential, added Dr. Di Biase, who’s also a member of the American College of Cardiology’s Electrophysiology Section Leadership Council. “If this application could predict the people that would develop diastolic dysfunction that leads to heart failure – because an echo at that time may be negative but there may be other features that tell me this patient will develop disease – then it would have a much different clinical impact.”
The National Science Foundation provided funding for the study. Heart Test Laboratories, doing business as Heart Sciences, provided funding and spECG devices. Dr. Kagiyama reported receiving a research grant from Hitachi Healthcare. A coauthor disclosed financial relationships with Heart Sciences, Ultronics, and Kencor Health.
Dr. Nasir, Dr. Khera, and Dr. Di Biase have no relevant financial relationships to disclose.
SOURCE: Kagiyama N et al. J Am Coll Cardiol. 2020;76:930-41.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
PVR reassessed as predictor of heart failure
A study of patients with pulmonary hypertension suggests a reconsideration of the accepted benchmark for pulmonary vascular hypertension as a predictor of heart failure may be warranted.
An elevated pulmonary vascular resistance of 3.0 Wood units or greater has been used as a prognostic marker for death and heart failure in pulmonary hypertension subgroups. But a large, multiyear study of a veterans population suggests that shifting that threshold to 2.2 Wood units in patients with right-heart catheterization may be justified.
Bradley A. Maron, MD, of the Veterans Affairs Boston Healthcare System and Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues evaluated 40,082 veterans in the VA Clinical Assessment, Reporting and Tracking (CART) program who had right-heart catheterization (RHC) in the VA system from Oct. 1, 2007, to Sept. 30, 2016.
“To our knowledge, these data provide the first evidence-based information on the continuum of clinical risk related to PVR in patients with elevated pulmonary artery pressure,” the researchers wrote. Their report was published online in Lancet Respiratory Medicine (2020 Jul 27. doi: 10.1016/S2213-2600(20)30317-9).
The retrospective cohort study found that all-cause mortality hazard ratio (HR), when adjusted for clinical variables, and mean pulmonary artery pressure (mPAP) increased progressively beginning at around 2.0 Wood units (WU). Clinically significant mortality HR emerged at 2.2 WU, with an adjusted risk 9% greater than a PVR of 2.1 Wood units (P < .0034), which the study considered the upper limit of normal PVR in health adults of a similar age range (61.5 to 73.5 years) as the study cohort. The researchers noted that a PVR of 3.0 WU has been the standard for forecasting outcomes in pulmonary hypertension (PH) (Eur Heart J. 2010;31:2915-57).
“Overall, these results suggest that reconsidering the hemodynamic parameters that define pulmonary hypertension in patients with cardiopulmonary disease is warranted, and they identify a need for early detection strategies to capture this large and vulnerable population,” the researchers wrote.
A subsequent analysis focused on patients with an mPAP of >19 mm HG (n = 32,725) and found that all-cause death when adjusted over a wide range of clinical variables that included PVR of 2.2 WU increased to a 25% HR. “However,” the researchers added, “a median cardiac output of < 4.0 L/min, which has been shown to be independently associated with adverse outcome, was present only when PVR was more than 4.0 Wood units.”
For a PVR of 2.2-3.0 WU, the median cardiac output was 4.87 L/min; for > 3.0 WU, it was 4.13 L/min. Among the patients with PVR > 2.2 WU (n = 15,780), 13.6% (n = 2,147) had an mPAP of 19-24 mm Hg.
In all patients with mPAP > 19 mm HG, pulmonary artery wedge pressure (PAWP) became a determining risk factor, with 15 mm HG the demarcation between low and high PAWP. At PVR of 2.2 WU, low-PAWP patients had a 52% greater adjusted risk of death and high-PAWP a 23% greater risk. At 4.0 WU, those adjusted risks rose dramatically – to 272% and 58%, for the low- and high-PAWP subgroups, respectively (P < .0001).
“Stratification of patients by PAWP had a major effect on outcome estimates in our study, illustrating the limitations of using the same PVR level to define clinical risk between precapillary and postcapillary pulmonary hypertension,” the researchers wrote.
They called for further study into how these findings impact people with PH but lower levels of cardiopulmonary disease than the cohort. “Overall, these findings support reconsidering the combination of hemodynamic variables used to identify patients with pulmonary hypertension,” the researchers stated.
The analyses of the VA CART database makes this “an interesting study,” said G. Hossein Almassi, MD, FCCP, of the Medical College of Wisconsin and Zablocki VA Medical Center in Milwaukee. “Within its limitation as a retrospective cohort study, the findings of a lower PVR and a lower mean PAP of > 19 mm being associated with increased risk of all-cause mortality and HF hospitalization are significant.”
He added: “Time will tell whether this will be an impetus for the clinicians to consider earlier therapeutic interventions in addition to lifestyle modification such as smoking cessation in this group of patients.”
Dr. Maron disclosed a financial relationship with Actelion.
SOURCE: Maron BA et al. Lancet Respir Med. 2020 Jul 27. doi: 10.1016/S2213-2600(20)30317-9.
A study of patients with pulmonary hypertension suggests a reconsideration of the accepted benchmark for pulmonary vascular hypertension as a predictor of heart failure may be warranted.
An elevated pulmonary vascular resistance of 3.0 Wood units or greater has been used as a prognostic marker for death and heart failure in pulmonary hypertension subgroups. But a large, multiyear study of a veterans population suggests that shifting that threshold to 2.2 Wood units in patients with right-heart catheterization may be justified.
Bradley A. Maron, MD, of the Veterans Affairs Boston Healthcare System and Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues evaluated 40,082 veterans in the VA Clinical Assessment, Reporting and Tracking (CART) program who had right-heart catheterization (RHC) in the VA system from Oct. 1, 2007, to Sept. 30, 2016.
“To our knowledge, these data provide the first evidence-based information on the continuum of clinical risk related to PVR in patients with elevated pulmonary artery pressure,” the researchers wrote. Their report was published online in Lancet Respiratory Medicine (2020 Jul 27. doi: 10.1016/S2213-2600(20)30317-9).
The retrospective cohort study found that all-cause mortality hazard ratio (HR), when adjusted for clinical variables, and mean pulmonary artery pressure (mPAP) increased progressively beginning at around 2.0 Wood units (WU). Clinically significant mortality HR emerged at 2.2 WU, with an adjusted risk 9% greater than a PVR of 2.1 Wood units (P < .0034), which the study considered the upper limit of normal PVR in health adults of a similar age range (61.5 to 73.5 years) as the study cohort. The researchers noted that a PVR of 3.0 WU has been the standard for forecasting outcomes in pulmonary hypertension (PH) (Eur Heart J. 2010;31:2915-57).
“Overall, these results suggest that reconsidering the hemodynamic parameters that define pulmonary hypertension in patients with cardiopulmonary disease is warranted, and they identify a need for early detection strategies to capture this large and vulnerable population,” the researchers wrote.
A subsequent analysis focused on patients with an mPAP of >19 mm HG (n = 32,725) and found that all-cause death when adjusted over a wide range of clinical variables that included PVR of 2.2 WU increased to a 25% HR. “However,” the researchers added, “a median cardiac output of < 4.0 L/min, which has been shown to be independently associated with adverse outcome, was present only when PVR was more than 4.0 Wood units.”
For a PVR of 2.2-3.0 WU, the median cardiac output was 4.87 L/min; for > 3.0 WU, it was 4.13 L/min. Among the patients with PVR > 2.2 WU (n = 15,780), 13.6% (n = 2,147) had an mPAP of 19-24 mm Hg.
In all patients with mPAP > 19 mm HG, pulmonary artery wedge pressure (PAWP) became a determining risk factor, with 15 mm HG the demarcation between low and high PAWP. At PVR of 2.2 WU, low-PAWP patients had a 52% greater adjusted risk of death and high-PAWP a 23% greater risk. At 4.0 WU, those adjusted risks rose dramatically – to 272% and 58%, for the low- and high-PAWP subgroups, respectively (P < .0001).
“Stratification of patients by PAWP had a major effect on outcome estimates in our study, illustrating the limitations of using the same PVR level to define clinical risk between precapillary and postcapillary pulmonary hypertension,” the researchers wrote.
They called for further study into how these findings impact people with PH but lower levels of cardiopulmonary disease than the cohort. “Overall, these findings support reconsidering the combination of hemodynamic variables used to identify patients with pulmonary hypertension,” the researchers stated.
The analyses of the VA CART database makes this “an interesting study,” said G. Hossein Almassi, MD, FCCP, of the Medical College of Wisconsin and Zablocki VA Medical Center in Milwaukee. “Within its limitation as a retrospective cohort study, the findings of a lower PVR and a lower mean PAP of > 19 mm being associated with increased risk of all-cause mortality and HF hospitalization are significant.”
He added: “Time will tell whether this will be an impetus for the clinicians to consider earlier therapeutic interventions in addition to lifestyle modification such as smoking cessation in this group of patients.”
Dr. Maron disclosed a financial relationship with Actelion.
SOURCE: Maron BA et al. Lancet Respir Med. 2020 Jul 27. doi: 10.1016/S2213-2600(20)30317-9.
A study of patients with pulmonary hypertension suggests a reconsideration of the accepted benchmark for pulmonary vascular hypertension as a predictor of heart failure may be warranted.
An elevated pulmonary vascular resistance of 3.0 Wood units or greater has been used as a prognostic marker for death and heart failure in pulmonary hypertension subgroups. But a large, multiyear study of a veterans population suggests that shifting that threshold to 2.2 Wood units in patients with right-heart catheterization may be justified.
Bradley A. Maron, MD, of the Veterans Affairs Boston Healthcare System and Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues evaluated 40,082 veterans in the VA Clinical Assessment, Reporting and Tracking (CART) program who had right-heart catheterization (RHC) in the VA system from Oct. 1, 2007, to Sept. 30, 2016.
“To our knowledge, these data provide the first evidence-based information on the continuum of clinical risk related to PVR in patients with elevated pulmonary artery pressure,” the researchers wrote. Their report was published online in Lancet Respiratory Medicine (2020 Jul 27. doi: 10.1016/S2213-2600(20)30317-9).
The retrospective cohort study found that all-cause mortality hazard ratio (HR), when adjusted for clinical variables, and mean pulmonary artery pressure (mPAP) increased progressively beginning at around 2.0 Wood units (WU). Clinically significant mortality HR emerged at 2.2 WU, with an adjusted risk 9% greater than a PVR of 2.1 Wood units (P < .0034), which the study considered the upper limit of normal PVR in health adults of a similar age range (61.5 to 73.5 years) as the study cohort. The researchers noted that a PVR of 3.0 WU has been the standard for forecasting outcomes in pulmonary hypertension (PH) (Eur Heart J. 2010;31:2915-57).
“Overall, these results suggest that reconsidering the hemodynamic parameters that define pulmonary hypertension in patients with cardiopulmonary disease is warranted, and they identify a need for early detection strategies to capture this large and vulnerable population,” the researchers wrote.
A subsequent analysis focused on patients with an mPAP of >19 mm HG (n = 32,725) and found that all-cause death when adjusted over a wide range of clinical variables that included PVR of 2.2 WU increased to a 25% HR. “However,” the researchers added, “a median cardiac output of < 4.0 L/min, which has been shown to be independently associated with adverse outcome, was present only when PVR was more than 4.0 Wood units.”
For a PVR of 2.2-3.0 WU, the median cardiac output was 4.87 L/min; for > 3.0 WU, it was 4.13 L/min. Among the patients with PVR > 2.2 WU (n = 15,780), 13.6% (n = 2,147) had an mPAP of 19-24 mm Hg.
In all patients with mPAP > 19 mm HG, pulmonary artery wedge pressure (PAWP) became a determining risk factor, with 15 mm HG the demarcation between low and high PAWP. At PVR of 2.2 WU, low-PAWP patients had a 52% greater adjusted risk of death and high-PAWP a 23% greater risk. At 4.0 WU, those adjusted risks rose dramatically – to 272% and 58%, for the low- and high-PAWP subgroups, respectively (P < .0001).
“Stratification of patients by PAWP had a major effect on outcome estimates in our study, illustrating the limitations of using the same PVR level to define clinical risk between precapillary and postcapillary pulmonary hypertension,” the researchers wrote.
They called for further study into how these findings impact people with PH but lower levels of cardiopulmonary disease than the cohort. “Overall, these findings support reconsidering the combination of hemodynamic variables used to identify patients with pulmonary hypertension,” the researchers stated.
The analyses of the VA CART database makes this “an interesting study,” said G. Hossein Almassi, MD, FCCP, of the Medical College of Wisconsin and Zablocki VA Medical Center in Milwaukee. “Within its limitation as a retrospective cohort study, the findings of a lower PVR and a lower mean PAP of > 19 mm being associated with increased risk of all-cause mortality and HF hospitalization are significant.”
He added: “Time will tell whether this will be an impetus for the clinicians to consider earlier therapeutic interventions in addition to lifestyle modification such as smoking cessation in this group of patients.”
Dr. Maron disclosed a financial relationship with Actelion.
SOURCE: Maron BA et al. Lancet Respir Med. 2020 Jul 27. doi: 10.1016/S2213-2600(20)30317-9.
FROM LANCET RESPIRATORY MEDICINE
MSBase study validates therapy for relapse in secondary progressive MS
An observational cohort study of a prospective international database of patients with multiple sclerosis has reported that medical therapy can reduce disability progression in patients with active secondary progressive MS (SPMS) who are prone to inflammatory relapses.
The international researchers, led by Nathanial Lizak, MMBS, of the University of Melbourne, conducted the cohort study of 1,621 patients with SPMS from the MSBase international registry, which prospectively collected the information from 1995 to 2018. Their findings were published in JAMA Neurology.
“ wrote Dr. Lizak and colleagues of the MSBase Study Group.
Therapy’s impact on disease progression
To ensure that they had timely data on the early disease course of all study patients, they researchers only included patients whose diagnosis and first documented Expanded Disability Status Scale (EDSS) score were no more than 24 months apart. At SPMS conversion, 1,494 patients had an EDSS score of less than 7 (on a scale of 0-10); during the follow-up period, 267 of them (17.9%) crossed over the threshold of 7.
Dr. Lizak and colleagues noted that early treatment during relapsing remitting MS didn’t impact outcomes after SPMS conversion.
For evaluating the MS Severity Score (MSSS), the study split the cohort into three groups depending on the efficacy of therapy: low-efficacy treatments, mostly consisting of interferon-beta and glatiramer acetate; medium-efficacy treatments, mostly fingolimod and dimethyl fumarate; and high-efficacy treatments, predominately natalizumab and mitoxantrone.
The MSSS progression slope in the cohort had an average reduction of 0.02 points per year. “For patients who experienced superimposed relapses during SPMS, a reduced MSSS progression slope during SPMS was observed among those who received disease-modifying therapies for a greater proportion of time during SPMS,” Dr. Lizak and colleagues wrote.
MSSS progression slope reduction was more pronounced in the medium- and high-efficacy groups, with a reduction of beta 0.22 (P = .06) and 0.034 (P = .002), respectively.
“Based on our models, the level of disability in patients with active SPMS who are continuously treated with high-efficacy immunotherapies would progress more slowly in comparison with the general population with MS by a mean (standard deviation) of 1.56 (4.60) deciles over 10 years,” Dr. Lizak and colleagues wrote.
While the researchers cited a number of studies that didn’t support immunotherapy for SPMS, they also did cite the EXPAND trial to support treatment with siponimod in SPMS patients (Lancet. 2018;391:1263-73). The ASCEND trial of natalizumab enrolled a largely relapse-free cohort and found no link between treatment and disability progression in SPMS (Lancet Neurol. 2018;17:405-15), and a previous report by the MSBase Study Group found no benefit of therapy when adjusted for SPMS relapse rates (Neurology. 2017;89:1050-9).
“Together with the present study, the existing data converge on the suggestion that relapses during SPMS provide a therapeutic target and a marker of future response to immunotherapy during SPMS,” Dr. Lizak and colleagues wrote.
Challenging dogma
Commenting on the research, Mark Freedman, HBSc, MSc, MD, said that the MSBase study makes an important contribution to the literature on management of SPMS. “Up until this point we’ve been basing our assumptions on secondary progressive MS on natural history studies, which are actually quite old, dating back 20-30 years.” Dr. Freedman is senior scientist in the Neuroscience Program at the Ottawa Hospital Research Institute and professor of medicine in neurology at the University of Ottawa.
He said “the most damaging” of those studies was by the late Christian Confavreaux, MD, and colleagues in Lyon, France (N Engl J Med. 2000;343:1430-8), that reported relapses didn’t alter the progression of disability. “In other words, once you’re in EDSS of 4, it’s a runaway train; it doesn’t matter what you do,” Dr. Freedman said.
“That was kind of dogma for years,” he said. “The reason this publication is important is because it’s suggesting that’s not the case.” In other words, the MSBase cohort study is validating what neurologists have been doing in the real world for years: treating patients with SPMS who have relapses.
Dr Lizak reported receiving travel compensation from Merck outside the scope of the study. His coauthors reported numerous financial relationships.
SOURCE: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453
An observational cohort study of a prospective international database of patients with multiple sclerosis has reported that medical therapy can reduce disability progression in patients with active secondary progressive MS (SPMS) who are prone to inflammatory relapses.
The international researchers, led by Nathanial Lizak, MMBS, of the University of Melbourne, conducted the cohort study of 1,621 patients with SPMS from the MSBase international registry, which prospectively collected the information from 1995 to 2018. Their findings were published in JAMA Neurology.
“ wrote Dr. Lizak and colleagues of the MSBase Study Group.
Therapy’s impact on disease progression
To ensure that they had timely data on the early disease course of all study patients, they researchers only included patients whose diagnosis and first documented Expanded Disability Status Scale (EDSS) score were no more than 24 months apart. At SPMS conversion, 1,494 patients had an EDSS score of less than 7 (on a scale of 0-10); during the follow-up period, 267 of them (17.9%) crossed over the threshold of 7.
Dr. Lizak and colleagues noted that early treatment during relapsing remitting MS didn’t impact outcomes after SPMS conversion.
For evaluating the MS Severity Score (MSSS), the study split the cohort into three groups depending on the efficacy of therapy: low-efficacy treatments, mostly consisting of interferon-beta and glatiramer acetate; medium-efficacy treatments, mostly fingolimod and dimethyl fumarate; and high-efficacy treatments, predominately natalizumab and mitoxantrone.
The MSSS progression slope in the cohort had an average reduction of 0.02 points per year. “For patients who experienced superimposed relapses during SPMS, a reduced MSSS progression slope during SPMS was observed among those who received disease-modifying therapies for a greater proportion of time during SPMS,” Dr. Lizak and colleagues wrote.
MSSS progression slope reduction was more pronounced in the medium- and high-efficacy groups, with a reduction of beta 0.22 (P = .06) and 0.034 (P = .002), respectively.
“Based on our models, the level of disability in patients with active SPMS who are continuously treated with high-efficacy immunotherapies would progress more slowly in comparison with the general population with MS by a mean (standard deviation) of 1.56 (4.60) deciles over 10 years,” Dr. Lizak and colleagues wrote.
While the researchers cited a number of studies that didn’t support immunotherapy for SPMS, they also did cite the EXPAND trial to support treatment with siponimod in SPMS patients (Lancet. 2018;391:1263-73). The ASCEND trial of natalizumab enrolled a largely relapse-free cohort and found no link between treatment and disability progression in SPMS (Lancet Neurol. 2018;17:405-15), and a previous report by the MSBase Study Group found no benefit of therapy when adjusted for SPMS relapse rates (Neurology. 2017;89:1050-9).
“Together with the present study, the existing data converge on the suggestion that relapses during SPMS provide a therapeutic target and a marker of future response to immunotherapy during SPMS,” Dr. Lizak and colleagues wrote.
Challenging dogma
Commenting on the research, Mark Freedman, HBSc, MSc, MD, said that the MSBase study makes an important contribution to the literature on management of SPMS. “Up until this point we’ve been basing our assumptions on secondary progressive MS on natural history studies, which are actually quite old, dating back 20-30 years.” Dr. Freedman is senior scientist in the Neuroscience Program at the Ottawa Hospital Research Institute and professor of medicine in neurology at the University of Ottawa.
He said “the most damaging” of those studies was by the late Christian Confavreaux, MD, and colleagues in Lyon, France (N Engl J Med. 2000;343:1430-8), that reported relapses didn’t alter the progression of disability. “In other words, once you’re in EDSS of 4, it’s a runaway train; it doesn’t matter what you do,” Dr. Freedman said.
“That was kind of dogma for years,” he said. “The reason this publication is important is because it’s suggesting that’s not the case.” In other words, the MSBase cohort study is validating what neurologists have been doing in the real world for years: treating patients with SPMS who have relapses.
Dr Lizak reported receiving travel compensation from Merck outside the scope of the study. His coauthors reported numerous financial relationships.
SOURCE: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453
An observational cohort study of a prospective international database of patients with multiple sclerosis has reported that medical therapy can reduce disability progression in patients with active secondary progressive MS (SPMS) who are prone to inflammatory relapses.
The international researchers, led by Nathanial Lizak, MMBS, of the University of Melbourne, conducted the cohort study of 1,621 patients with SPMS from the MSBase international registry, which prospectively collected the information from 1995 to 2018. Their findings were published in JAMA Neurology.
“ wrote Dr. Lizak and colleagues of the MSBase Study Group.
Therapy’s impact on disease progression
To ensure that they had timely data on the early disease course of all study patients, they researchers only included patients whose diagnosis and first documented Expanded Disability Status Scale (EDSS) score were no more than 24 months apart. At SPMS conversion, 1,494 patients had an EDSS score of less than 7 (on a scale of 0-10); during the follow-up period, 267 of them (17.9%) crossed over the threshold of 7.
Dr. Lizak and colleagues noted that early treatment during relapsing remitting MS didn’t impact outcomes after SPMS conversion.
For evaluating the MS Severity Score (MSSS), the study split the cohort into three groups depending on the efficacy of therapy: low-efficacy treatments, mostly consisting of interferon-beta and glatiramer acetate; medium-efficacy treatments, mostly fingolimod and dimethyl fumarate; and high-efficacy treatments, predominately natalizumab and mitoxantrone.
The MSSS progression slope in the cohort had an average reduction of 0.02 points per year. “For patients who experienced superimposed relapses during SPMS, a reduced MSSS progression slope during SPMS was observed among those who received disease-modifying therapies for a greater proportion of time during SPMS,” Dr. Lizak and colleagues wrote.
MSSS progression slope reduction was more pronounced in the medium- and high-efficacy groups, with a reduction of beta 0.22 (P = .06) and 0.034 (P = .002), respectively.
“Based on our models, the level of disability in patients with active SPMS who are continuously treated with high-efficacy immunotherapies would progress more slowly in comparison with the general population with MS by a mean (standard deviation) of 1.56 (4.60) deciles over 10 years,” Dr. Lizak and colleagues wrote.
While the researchers cited a number of studies that didn’t support immunotherapy for SPMS, they also did cite the EXPAND trial to support treatment with siponimod in SPMS patients (Lancet. 2018;391:1263-73). The ASCEND trial of natalizumab enrolled a largely relapse-free cohort and found no link between treatment and disability progression in SPMS (Lancet Neurol. 2018;17:405-15), and a previous report by the MSBase Study Group found no benefit of therapy when adjusted for SPMS relapse rates (Neurology. 2017;89:1050-9).
“Together with the present study, the existing data converge on the suggestion that relapses during SPMS provide a therapeutic target and a marker of future response to immunotherapy during SPMS,” Dr. Lizak and colleagues wrote.
Challenging dogma
Commenting on the research, Mark Freedman, HBSc, MSc, MD, said that the MSBase study makes an important contribution to the literature on management of SPMS. “Up until this point we’ve been basing our assumptions on secondary progressive MS on natural history studies, which are actually quite old, dating back 20-30 years.” Dr. Freedman is senior scientist in the Neuroscience Program at the Ottawa Hospital Research Institute and professor of medicine in neurology at the University of Ottawa.
He said “the most damaging” of those studies was by the late Christian Confavreaux, MD, and colleagues in Lyon, France (N Engl J Med. 2000;343:1430-8), that reported relapses didn’t alter the progression of disability. “In other words, once you’re in EDSS of 4, it’s a runaway train; it doesn’t matter what you do,” Dr. Freedman said.
“That was kind of dogma for years,” he said. “The reason this publication is important is because it’s suggesting that’s not the case.” In other words, the MSBase cohort study is validating what neurologists have been doing in the real world for years: treating patients with SPMS who have relapses.
Dr Lizak reported receiving travel compensation from Merck outside the scope of the study. His coauthors reported numerous financial relationships.
SOURCE: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453
FROM JAMA NEUROLOGY
ACC panel defines, advises on heart failure with ‘recovered’ EF
Because heart failure patients with recovered ejection fraction are a complex and diverse group, little consensus has emerged on how to define, diagnose, and manage this growing population.
To provide some clarity for identifying and treating these patients, a Journal of the American College of Cardiology scientific expert panel has issued a consensus document. Published Aug. 3 in the Journal of the American College of Cardiology, it provides a working definition of heart failure with recovered ejection fraction (HFrecEF) and recommends approaches for treatment and follow-up.
Defining a new class of HF
“Part of the impetus of this was to bring attention to what we think is a new class of heart failure, and it requires different treatment modalities and different ways of thinking about it,” expert panel member Douglas L. Mann, MD, cardiologist-in-chief at Barnes Jewish Hospital in St. Louis, said in an interview. “It’s a newly discovered HF biology about which we know very little and it’s very confusing to just go on the ejection fraction alone.”
The panel, led by Jane E. Wilcox, MD, of Northwestern University, Chicago, recommends three components for a working definition of HFrecEF: 1) documentation of a decreased left ventricle ejection fraction (LVEF) of less than 40% at baseline; 2) a 10% or greater absolute improvement in LVEF; and 3) a second measurement of LVEF >40%.
“We try to give it a nomenclature that clearly indicates what it is,” Dr. Mann said. “There has been a lot of confusing terminology.” Among the terms the panel calls out in the lexicon of modestly recovered EF, in addition to HFrecEF, are HF improved EF, HF with preserved EF (HFpEF), borderline HFpEF and HF with mid-range EF (HFmrEF).
The panel also recommends that guideline-based medical and device therapies for HFrecEF should continue indefinitely until there’s a better understanding of the biology and clinical epidemiology of HFrecEF, and that these patients should have close clinical follow-up because of the high risk of HF relapse.
Determining EF’s ‘trajectory’
The findings presented in the statement should help cardiologists distinguish HFrecEF from HFpEF, Dr. Mann noted. “Because EF is moving, we also have to emphasize the importance of following the trajectory of EF,” he said. “It’s not enough to know where the EF is; you have to know where it came from – if it had been from a higher number or a lower number – because that will help inform you about the patient’s disease.”
In that regard, the panel states that the level of change in LVEF – the “trajectory” – will provide clues to the nature and extent of myocardial injury, degree and duration of LV remodeling, and the type of therapy that’s indicated. Clinicians should consider HFmrEF, a description the European Society of Cardiology has endorsed, as an entity different from HFrecEF without data on LVEF trajectory.
The statement delves into the biology of HFrecEF, defining reverse LV remodeling as the restoration of some normalization to cardiac myocyte size and LV chamber geometry that results in a leftward shift toward normalization of end-diastolic pressure volume. The panel also noted that cardiac remodeling in reverse LV remodeling and recovery of LV function is bidirectional and involves multiple molecular and cellular changes that contribute to changes in the heart’s size, shape and function, and explains the role gene expression has in HF-related LV changes.
The statement explores the recovery of LV function, noting that spontaneous recovery often occurs when the cause of the myocardial dysfunction resolves. Common causes are chronic tachycardia and thyroid disease.
That panel noted that “super responders” to cardiac resynchronization therapy can provide insight into HFrecEF. Favorable responders include women, patients with nonischemic HF, very wide ECG ventricular depolarization wavelength with left-bundle branch block morphology, and dyssynchrony on ECG.
The panel states that, “regardless of the definition of HFrecEF,” the evidence suggests that younger patients, women, and those with nonischemic disease, shorter disease duration, and relatively few comorbidities are more likely to recover LVEF – and their outcomes are typically better than those of patients with HF reduced EF (HFrEF) and HFpEF.
Clinicians should bear in mind, however, that patients on guideline-directed medical therapy (GDMT) who achieve complete normalization of LV structure and function are prone to recurrent LV dysfunction and HF. The panel explored the role of potential treatment for three different etiologies of HF. Little is known about Takotsubo cardiomyopathy, considered a transient form of LV dysfunction, in terms of how many of these patients will develop HFrEF or if they’ll benefit from GDMT. Alcohol-induced cardiomyopathy patients should continue on medical therapy even if they have HFrecEF, as should patients with fulminant and nonfulminant myocarditis.
Managing HFrecEF
Management should include assessment of jugular vein distention and signs of volume overload – “particularly concerning in HFrecEF” – the panel noted. ECG is cost effective, and signs of left-bundle branch block are predictors of low success with GDMT alone. The panel also recommended a family history going back three generations and consideration of genetic testing to determine the risk for sudden cardiac death. Two-dimensional ECG can help predict GDMT response and cardiovascular magnetic resonance imaging can provide information about myocardial substrate at the time of diagnosis of HFrEF.
The panel suggested four areas for future research: 1) improved phenotyping of HFrEF; 2) use of inception cohorts to better understand the natural history of HFrecEF; 3) clinical trials to better define those clinical care components most effective at maintaining remission; and 4) basic studies to better define the biology of HFrecEF. “The goal,” wrote Dr. Wilcox and colleagues, “is to develop new therapeutic targets that will enable patients with HFrecEF to experience a durable remission from HF.”
Dr. Wilcox reported receiving funding from the National Institutes of Health and the American Heart Association, and financial relationships with Abbott, Medtronic, and Cytokinetics. Dr. Mann has received funding from NIH and reports financial relationships with MyoKardia and Novartis. Coauthors reported funding from NIH and AHA and financial relationships with Novartis, Amgen, AstraZeneca, Thoratec Corporation (Abbott), Sanofi, Pfizer, MyoKardia and American Regent.
SOURCE: Wilcox JE et al. J Am Coll Cardiol. 2020;76:719-34.
Because heart failure patients with recovered ejection fraction are a complex and diverse group, little consensus has emerged on how to define, diagnose, and manage this growing population.
To provide some clarity for identifying and treating these patients, a Journal of the American College of Cardiology scientific expert panel has issued a consensus document. Published Aug. 3 in the Journal of the American College of Cardiology, it provides a working definition of heart failure with recovered ejection fraction (HFrecEF) and recommends approaches for treatment and follow-up.
Defining a new class of HF
“Part of the impetus of this was to bring attention to what we think is a new class of heart failure, and it requires different treatment modalities and different ways of thinking about it,” expert panel member Douglas L. Mann, MD, cardiologist-in-chief at Barnes Jewish Hospital in St. Louis, said in an interview. “It’s a newly discovered HF biology about which we know very little and it’s very confusing to just go on the ejection fraction alone.”
The panel, led by Jane E. Wilcox, MD, of Northwestern University, Chicago, recommends three components for a working definition of HFrecEF: 1) documentation of a decreased left ventricle ejection fraction (LVEF) of less than 40% at baseline; 2) a 10% or greater absolute improvement in LVEF; and 3) a second measurement of LVEF >40%.
“We try to give it a nomenclature that clearly indicates what it is,” Dr. Mann said. “There has been a lot of confusing terminology.” Among the terms the panel calls out in the lexicon of modestly recovered EF, in addition to HFrecEF, are HF improved EF, HF with preserved EF (HFpEF), borderline HFpEF and HF with mid-range EF (HFmrEF).
The panel also recommends that guideline-based medical and device therapies for HFrecEF should continue indefinitely until there’s a better understanding of the biology and clinical epidemiology of HFrecEF, and that these patients should have close clinical follow-up because of the high risk of HF relapse.
Determining EF’s ‘trajectory’
The findings presented in the statement should help cardiologists distinguish HFrecEF from HFpEF, Dr. Mann noted. “Because EF is moving, we also have to emphasize the importance of following the trajectory of EF,” he said. “It’s not enough to know where the EF is; you have to know where it came from – if it had been from a higher number or a lower number – because that will help inform you about the patient’s disease.”
In that regard, the panel states that the level of change in LVEF – the “trajectory” – will provide clues to the nature and extent of myocardial injury, degree and duration of LV remodeling, and the type of therapy that’s indicated. Clinicians should consider HFmrEF, a description the European Society of Cardiology has endorsed, as an entity different from HFrecEF without data on LVEF trajectory.
The statement delves into the biology of HFrecEF, defining reverse LV remodeling as the restoration of some normalization to cardiac myocyte size and LV chamber geometry that results in a leftward shift toward normalization of end-diastolic pressure volume. The panel also noted that cardiac remodeling in reverse LV remodeling and recovery of LV function is bidirectional and involves multiple molecular and cellular changes that contribute to changes in the heart’s size, shape and function, and explains the role gene expression has in HF-related LV changes.
The statement explores the recovery of LV function, noting that spontaneous recovery often occurs when the cause of the myocardial dysfunction resolves. Common causes are chronic tachycardia and thyroid disease.
That panel noted that “super responders” to cardiac resynchronization therapy can provide insight into HFrecEF. Favorable responders include women, patients with nonischemic HF, very wide ECG ventricular depolarization wavelength with left-bundle branch block morphology, and dyssynchrony on ECG.
The panel states that, “regardless of the definition of HFrecEF,” the evidence suggests that younger patients, women, and those with nonischemic disease, shorter disease duration, and relatively few comorbidities are more likely to recover LVEF – and their outcomes are typically better than those of patients with HF reduced EF (HFrEF) and HFpEF.
Clinicians should bear in mind, however, that patients on guideline-directed medical therapy (GDMT) who achieve complete normalization of LV structure and function are prone to recurrent LV dysfunction and HF. The panel explored the role of potential treatment for three different etiologies of HF. Little is known about Takotsubo cardiomyopathy, considered a transient form of LV dysfunction, in terms of how many of these patients will develop HFrEF or if they’ll benefit from GDMT. Alcohol-induced cardiomyopathy patients should continue on medical therapy even if they have HFrecEF, as should patients with fulminant and nonfulminant myocarditis.
Managing HFrecEF
Management should include assessment of jugular vein distention and signs of volume overload – “particularly concerning in HFrecEF” – the panel noted. ECG is cost effective, and signs of left-bundle branch block are predictors of low success with GDMT alone. The panel also recommended a family history going back three generations and consideration of genetic testing to determine the risk for sudden cardiac death. Two-dimensional ECG can help predict GDMT response and cardiovascular magnetic resonance imaging can provide information about myocardial substrate at the time of diagnosis of HFrEF.
The panel suggested four areas for future research: 1) improved phenotyping of HFrEF; 2) use of inception cohorts to better understand the natural history of HFrecEF; 3) clinical trials to better define those clinical care components most effective at maintaining remission; and 4) basic studies to better define the biology of HFrecEF. “The goal,” wrote Dr. Wilcox and colleagues, “is to develop new therapeutic targets that will enable patients with HFrecEF to experience a durable remission from HF.”
Dr. Wilcox reported receiving funding from the National Institutes of Health and the American Heart Association, and financial relationships with Abbott, Medtronic, and Cytokinetics. Dr. Mann has received funding from NIH and reports financial relationships with MyoKardia and Novartis. Coauthors reported funding from NIH and AHA and financial relationships with Novartis, Amgen, AstraZeneca, Thoratec Corporation (Abbott), Sanofi, Pfizer, MyoKardia and American Regent.
SOURCE: Wilcox JE et al. J Am Coll Cardiol. 2020;76:719-34.
Because heart failure patients with recovered ejection fraction are a complex and diverse group, little consensus has emerged on how to define, diagnose, and manage this growing population.
To provide some clarity for identifying and treating these patients, a Journal of the American College of Cardiology scientific expert panel has issued a consensus document. Published Aug. 3 in the Journal of the American College of Cardiology, it provides a working definition of heart failure with recovered ejection fraction (HFrecEF) and recommends approaches for treatment and follow-up.
Defining a new class of HF
“Part of the impetus of this was to bring attention to what we think is a new class of heart failure, and it requires different treatment modalities and different ways of thinking about it,” expert panel member Douglas L. Mann, MD, cardiologist-in-chief at Barnes Jewish Hospital in St. Louis, said in an interview. “It’s a newly discovered HF biology about which we know very little and it’s very confusing to just go on the ejection fraction alone.”
The panel, led by Jane E. Wilcox, MD, of Northwestern University, Chicago, recommends three components for a working definition of HFrecEF: 1) documentation of a decreased left ventricle ejection fraction (LVEF) of less than 40% at baseline; 2) a 10% or greater absolute improvement in LVEF; and 3) a second measurement of LVEF >40%.
“We try to give it a nomenclature that clearly indicates what it is,” Dr. Mann said. “There has been a lot of confusing terminology.” Among the terms the panel calls out in the lexicon of modestly recovered EF, in addition to HFrecEF, are HF improved EF, HF with preserved EF (HFpEF), borderline HFpEF and HF with mid-range EF (HFmrEF).
The panel also recommends that guideline-based medical and device therapies for HFrecEF should continue indefinitely until there’s a better understanding of the biology and clinical epidemiology of HFrecEF, and that these patients should have close clinical follow-up because of the high risk of HF relapse.
Determining EF’s ‘trajectory’
The findings presented in the statement should help cardiologists distinguish HFrecEF from HFpEF, Dr. Mann noted. “Because EF is moving, we also have to emphasize the importance of following the trajectory of EF,” he said. “It’s not enough to know where the EF is; you have to know where it came from – if it had been from a higher number or a lower number – because that will help inform you about the patient’s disease.”
In that regard, the panel states that the level of change in LVEF – the “trajectory” – will provide clues to the nature and extent of myocardial injury, degree and duration of LV remodeling, and the type of therapy that’s indicated. Clinicians should consider HFmrEF, a description the European Society of Cardiology has endorsed, as an entity different from HFrecEF without data on LVEF trajectory.
The statement delves into the biology of HFrecEF, defining reverse LV remodeling as the restoration of some normalization to cardiac myocyte size and LV chamber geometry that results in a leftward shift toward normalization of end-diastolic pressure volume. The panel also noted that cardiac remodeling in reverse LV remodeling and recovery of LV function is bidirectional and involves multiple molecular and cellular changes that contribute to changes in the heart’s size, shape and function, and explains the role gene expression has in HF-related LV changes.
The statement explores the recovery of LV function, noting that spontaneous recovery often occurs when the cause of the myocardial dysfunction resolves. Common causes are chronic tachycardia and thyroid disease.
That panel noted that “super responders” to cardiac resynchronization therapy can provide insight into HFrecEF. Favorable responders include women, patients with nonischemic HF, very wide ECG ventricular depolarization wavelength with left-bundle branch block morphology, and dyssynchrony on ECG.
The panel states that, “regardless of the definition of HFrecEF,” the evidence suggests that younger patients, women, and those with nonischemic disease, shorter disease duration, and relatively few comorbidities are more likely to recover LVEF – and their outcomes are typically better than those of patients with HF reduced EF (HFrEF) and HFpEF.
Clinicians should bear in mind, however, that patients on guideline-directed medical therapy (GDMT) who achieve complete normalization of LV structure and function are prone to recurrent LV dysfunction and HF. The panel explored the role of potential treatment for three different etiologies of HF. Little is known about Takotsubo cardiomyopathy, considered a transient form of LV dysfunction, in terms of how many of these patients will develop HFrEF or if they’ll benefit from GDMT. Alcohol-induced cardiomyopathy patients should continue on medical therapy even if they have HFrecEF, as should patients with fulminant and nonfulminant myocarditis.
Managing HFrecEF
Management should include assessment of jugular vein distention and signs of volume overload – “particularly concerning in HFrecEF” – the panel noted. ECG is cost effective, and signs of left-bundle branch block are predictors of low success with GDMT alone. The panel also recommended a family history going back three generations and consideration of genetic testing to determine the risk for sudden cardiac death. Two-dimensional ECG can help predict GDMT response and cardiovascular magnetic resonance imaging can provide information about myocardial substrate at the time of diagnosis of HFrEF.
The panel suggested four areas for future research: 1) improved phenotyping of HFrEF; 2) use of inception cohorts to better understand the natural history of HFrecEF; 3) clinical trials to better define those clinical care components most effective at maintaining remission; and 4) basic studies to better define the biology of HFrecEF. “The goal,” wrote Dr. Wilcox and colleagues, “is to develop new therapeutic targets that will enable patients with HFrecEF to experience a durable remission from HF.”
Dr. Wilcox reported receiving funding from the National Institutes of Health and the American Heart Association, and financial relationships with Abbott, Medtronic, and Cytokinetics. Dr. Mann has received funding from NIH and reports financial relationships with MyoKardia and Novartis. Coauthors reported funding from NIH and AHA and financial relationships with Novartis, Amgen, AstraZeneca, Thoratec Corporation (Abbott), Sanofi, Pfizer, MyoKardia and American Regent.
SOURCE: Wilcox JE et al. J Am Coll Cardiol. 2020;76:719-34.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Most younger MI patients wouldn’t get statins under guidelines
Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.
“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”
The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).
The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.
The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.
“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
Key findings
The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).
Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).
After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).
The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”
How to protect younger patients
“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.
“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.
Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.
Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.”
The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).
“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.
Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.
SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.
Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.
“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”
The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).
The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.
The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.
“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
Key findings
The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).
Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).
After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).
The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”
How to protect younger patients
“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.
“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.
Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.
Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.”
The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).
“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.
Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.
SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.
Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.
“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”
The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).
The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.
The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.
“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
Key findings
The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).
Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).
After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).
The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”
How to protect younger patients
“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.
“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.
Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.
Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.”
The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).
“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.
Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.
SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
AHA statement addresses genetic testing for CVD
A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.
The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.
Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”
The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”
The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.
“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.
The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.
After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.
But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.
Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”
Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.
According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.
The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.
Dr. Musunuru and writing group members have no relevant financial relationships to disclose.
SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.
A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.
The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.
Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”
The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”
The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.
“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.
The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.
After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.
But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.
Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”
Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.
According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.
The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.
Dr. Musunuru and writing group members have no relevant financial relationships to disclose.
SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.
A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.
The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.
Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”
The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”
The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.
“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.
The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.
After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.
But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.
Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”
Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.
According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.
The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.
Dr. Musunuru and writing group members have no relevant financial relationships to disclose.
SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.
FROM CIRCULATION: GENOMIC AND PRECISION MEDICINE
Hypertension medication adjustment less likely with polypill
A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.
However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.
The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.
A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).
The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.
“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.
“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.
The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.
Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.
“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.
In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.
“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”
Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.
SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.
A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.
However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.
The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.
A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).
The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.
“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.
“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.
The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.
Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.
“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.
In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.
“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”
Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.
SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.
A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.
However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.
The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.
A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).
The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.
“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.
“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.
The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.
Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.
“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.
In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.
“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”
Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.
SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.
FROM JAMA CARDIOLOGY
Wear N95 masks during endoscopy
COVID-19 guideline update
Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.
The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.
The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:
1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).
2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).
3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).
4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).
For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.
For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.
Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.
The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.
“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”
For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.
The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.
The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.
There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.
SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.
Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.
COVID-19 guideline update
COVID-19 guideline update
Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.
The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.
The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:
1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).
2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).
3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).
4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).
For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.
For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.
Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.
The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.
“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”
For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.
The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.
The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.
There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.
SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.
Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.
Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.
The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.
The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:
1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).
2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).
3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).
4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).
For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.
For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.
Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.
The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.
“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”
For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.
The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.
The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.
There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.
SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.
Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.
Commonalities challenge the threshold of high-frequency episodic and low-frequency chronic migraine
according to an analysis of almost 17,000 patients from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study presented at the virtual annual meeting of the American Headache Society.
“The results showed substantial overlap in levels of burden, anxiety, depression and health utilization, including outpatient, inpatient and emergency department visits, among CaMEO respondents with high-frequency episodic migraine and those with low-frequency chronic migraine,” said Richard B. Lipton, MD, of the Albert Einstein College of Medicine, New York.
The study analyzed data on 16,789 respondents to CaMEO, the longitudinal, web-based study designed to characterize the course of episodic and chronic migraine. The study population consisted of four subgroups based on the number of self-reporting monthly headache days (MHDs):
- Low- and moderate-frequency episodic migraine (LFEM; zero to seven MHDs; n = 13,473).
- High-frequency episodic migraine (HFEM; 8-14 MHDs; n = 1,840).
- Low-frequency chronic migraine (LFCM; 15-23 MHDs; n = 1,035).
- High-frequency chronic migraine (HFCM; 24 or more MHDs; n = 441).
Dr. Lipton pointed out that the International Classification of Headache Disorders, 3rd edition, defines chronic migraine as 15 or more MHDs for 3 months or more with criteria for migraine with or without aura met on 8 days a month or more. It defines episodic migraine as less than 15 MHDs.
The study characterized migraine subgroups by various demographics. “The more frequent headache categories were associated with slightly older age of onset with a higher proportion of BMI [body mass index] in the obese range and overall with lower levels of household income and education,” Dr. Lipton said.
Similar headache characteristics
A comparison of headache characteristics and headache-related disabilities across subgroups revealed a number of commonalities between the HFEM and LFCM subgroups, Dr. Lipton said. Among them were presence of mild to severe allodynia, disability grade, interictal burden, and anxiety and depression scores. For example, 47.3% of the HFEM subgroup and 54.9% of the LFCM subgroup had Patient Health Questionnaire–9 depression test scores greater than 10.
The study also evaluated patterns of consultation, diagnosis, and health resource utilization and found similar rates between the HFEM and LCFM subgroups, Dr. Lipton said. Rates of overnight hospital stay in the past 6 months were almost identical between the two subgroups: 4.1% for the former and 4.2% for the latter. One striking difference between the two subgroups: the rate of medication overuse per ICHD-3 recommendations was 40.5% in HFEM and 63% in LFCM.
“These finding suggest that the treatment needs of people with HFEM may be similar to those of people with LFCM, suggesting that the 15-MHD threshold currently recommended by the ICHD-3 may merit reconsideration,” Dr. Lipton said.
An arbitrary cutoff?
The findings raise a valid point about reevaluating the thresholds for low- and high-frequency migraine, said Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles. “My own personal view is that they’re the same thing,” he said of HFEM and LFCM; The 15-day cutoff, he said, is “somewhat arbitrary.”
Dr. Charles suggested migraine categories address frequency and not characteristics – episodic versus chronic – and use a range rather than a threshold. “Define a range that’s more like 10-20 days per month rather than having that point at 15,” Dr. Charles said. “People sometimes make the mistake of thinking that that classification reflects some underlying pathophysiology, and that may not be necessarily true.”
Dr. Lipton disclosed financial relationships with Alder Biopharmaceuticals, Allergan (now AbbVie), Amgen, Biohaven Pharmaceuticals, Dr. Reddy’s/Promius, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Lundbeck (Alder), Merck, Pernix Therapeutics, Pfizer, Supernus, Teva, Trigemina, Axsome Therapeutics, Vector, and Vedanta. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.
according to an analysis of almost 17,000 patients from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study presented at the virtual annual meeting of the American Headache Society.
“The results showed substantial overlap in levels of burden, anxiety, depression and health utilization, including outpatient, inpatient and emergency department visits, among CaMEO respondents with high-frequency episodic migraine and those with low-frequency chronic migraine,” said Richard B. Lipton, MD, of the Albert Einstein College of Medicine, New York.
The study analyzed data on 16,789 respondents to CaMEO, the longitudinal, web-based study designed to characterize the course of episodic and chronic migraine. The study population consisted of four subgroups based on the number of self-reporting monthly headache days (MHDs):
- Low- and moderate-frequency episodic migraine (LFEM; zero to seven MHDs; n = 13,473).
- High-frequency episodic migraine (HFEM; 8-14 MHDs; n = 1,840).
- Low-frequency chronic migraine (LFCM; 15-23 MHDs; n = 1,035).
- High-frequency chronic migraine (HFCM; 24 or more MHDs; n = 441).
Dr. Lipton pointed out that the International Classification of Headache Disorders, 3rd edition, defines chronic migraine as 15 or more MHDs for 3 months or more with criteria for migraine with or without aura met on 8 days a month or more. It defines episodic migraine as less than 15 MHDs.
The study characterized migraine subgroups by various demographics. “The more frequent headache categories were associated with slightly older age of onset with a higher proportion of BMI [body mass index] in the obese range and overall with lower levels of household income and education,” Dr. Lipton said.
Similar headache characteristics
A comparison of headache characteristics and headache-related disabilities across subgroups revealed a number of commonalities between the HFEM and LFCM subgroups, Dr. Lipton said. Among them were presence of mild to severe allodynia, disability grade, interictal burden, and anxiety and depression scores. For example, 47.3% of the HFEM subgroup and 54.9% of the LFCM subgroup had Patient Health Questionnaire–9 depression test scores greater than 10.
The study also evaluated patterns of consultation, diagnosis, and health resource utilization and found similar rates between the HFEM and LCFM subgroups, Dr. Lipton said. Rates of overnight hospital stay in the past 6 months were almost identical between the two subgroups: 4.1% for the former and 4.2% for the latter. One striking difference between the two subgroups: the rate of medication overuse per ICHD-3 recommendations was 40.5% in HFEM and 63% in LFCM.
“These finding suggest that the treatment needs of people with HFEM may be similar to those of people with LFCM, suggesting that the 15-MHD threshold currently recommended by the ICHD-3 may merit reconsideration,” Dr. Lipton said.
An arbitrary cutoff?
The findings raise a valid point about reevaluating the thresholds for low- and high-frequency migraine, said Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles. “My own personal view is that they’re the same thing,” he said of HFEM and LFCM; The 15-day cutoff, he said, is “somewhat arbitrary.”
Dr. Charles suggested migraine categories address frequency and not characteristics – episodic versus chronic – and use a range rather than a threshold. “Define a range that’s more like 10-20 days per month rather than having that point at 15,” Dr. Charles said. “People sometimes make the mistake of thinking that that classification reflects some underlying pathophysiology, and that may not be necessarily true.”
Dr. Lipton disclosed financial relationships with Alder Biopharmaceuticals, Allergan (now AbbVie), Amgen, Biohaven Pharmaceuticals, Dr. Reddy’s/Promius, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Lundbeck (Alder), Merck, Pernix Therapeutics, Pfizer, Supernus, Teva, Trigemina, Axsome Therapeutics, Vector, and Vedanta. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.
according to an analysis of almost 17,000 patients from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study presented at the virtual annual meeting of the American Headache Society.
“The results showed substantial overlap in levels of burden, anxiety, depression and health utilization, including outpatient, inpatient and emergency department visits, among CaMEO respondents with high-frequency episodic migraine and those with low-frequency chronic migraine,” said Richard B. Lipton, MD, of the Albert Einstein College of Medicine, New York.
The study analyzed data on 16,789 respondents to CaMEO, the longitudinal, web-based study designed to characterize the course of episodic and chronic migraine. The study population consisted of four subgroups based on the number of self-reporting monthly headache days (MHDs):
- Low- and moderate-frequency episodic migraine (LFEM; zero to seven MHDs; n = 13,473).
- High-frequency episodic migraine (HFEM; 8-14 MHDs; n = 1,840).
- Low-frequency chronic migraine (LFCM; 15-23 MHDs; n = 1,035).
- High-frequency chronic migraine (HFCM; 24 or more MHDs; n = 441).
Dr. Lipton pointed out that the International Classification of Headache Disorders, 3rd edition, defines chronic migraine as 15 or more MHDs for 3 months or more with criteria for migraine with or without aura met on 8 days a month or more. It defines episodic migraine as less than 15 MHDs.
The study characterized migraine subgroups by various demographics. “The more frequent headache categories were associated with slightly older age of onset with a higher proportion of BMI [body mass index] in the obese range and overall with lower levels of household income and education,” Dr. Lipton said.
Similar headache characteristics
A comparison of headache characteristics and headache-related disabilities across subgroups revealed a number of commonalities between the HFEM and LFCM subgroups, Dr. Lipton said. Among them were presence of mild to severe allodynia, disability grade, interictal burden, and anxiety and depression scores. For example, 47.3% of the HFEM subgroup and 54.9% of the LFCM subgroup had Patient Health Questionnaire–9 depression test scores greater than 10.
The study also evaluated patterns of consultation, diagnosis, and health resource utilization and found similar rates between the HFEM and LCFM subgroups, Dr. Lipton said. Rates of overnight hospital stay in the past 6 months were almost identical between the two subgroups: 4.1% for the former and 4.2% for the latter. One striking difference between the two subgroups: the rate of medication overuse per ICHD-3 recommendations was 40.5% in HFEM and 63% in LFCM.
“These finding suggest that the treatment needs of people with HFEM may be similar to those of people with LFCM, suggesting that the 15-MHD threshold currently recommended by the ICHD-3 may merit reconsideration,” Dr. Lipton said.
An arbitrary cutoff?
The findings raise a valid point about reevaluating the thresholds for low- and high-frequency migraine, said Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles. “My own personal view is that they’re the same thing,” he said of HFEM and LFCM; The 15-day cutoff, he said, is “somewhat arbitrary.”
Dr. Charles suggested migraine categories address frequency and not characteristics – episodic versus chronic – and use a range rather than a threshold. “Define a range that’s more like 10-20 days per month rather than having that point at 15,” Dr. Charles said. “People sometimes make the mistake of thinking that that classification reflects some underlying pathophysiology, and that may not be necessarily true.”
Dr. Lipton disclosed financial relationships with Alder Biopharmaceuticals, Allergan (now AbbVie), Amgen, Biohaven Pharmaceuticals, Dr. Reddy’s/Promius, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Lundbeck (Alder), Merck, Pernix Therapeutics, Pfizer, Supernus, Teva, Trigemina, Axsome Therapeutics, Vector, and Vedanta. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.
FROM AHS 2020