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EHR nudges a bust for boosting guideline-directed meds in acute HF: PROMPT-AHF
in a randomized trial conducted at several centers in the same health care system.
The results of the PROMPT-AHF trial, which assigned such patients to have or not have the GDMT-promoting physician nudges as part of their in-hospital management, were “not entirely surprising,” Tariq Ahmad, MD, MPH, of Yale University, New Haven, Conn., said in an interview.
“We have created an environment in the hospital that makes care quite fractured for patients with heart failure,” he said. “They are cared for by many different clinicians, which leads to well-known behaviors such as diffusion of responsibility.”
Moreover, many clinicians focus on stabilizing patients “rather than starting them on a comprehensive set of medications, which most think should be done after discharge,” Dr. Ahmad added.
“Importantly, there has been a logarithmic increase in alerts while patients are hospitalized that has caused clinician burnout and is leading to even very important alerts being ignored.”
Likely as a result, the trial saw no significant difference between the alert and no-alert groups in how often the number of GDMT prescriptions rose by at least one drug class, whether beta blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, or SGLT2 inhibitors. That happened for 34% of patients in both groups, reported Dr. Ahmad at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions
Nor was there a difference in the secondary endpoint of increased number of GDMT meds or escalated dosage of prescribed GDMT drugs.
GDMT ‘uncommon’ in AHF
In an earlier trial in outpatients with chronic HF, conducted by many of the same researchers, use of a targeted EHR-based alert system was associated with significantly higher rates of GDMT prescriptions 30 days after discharge, compared with usual care, Dr. Ahmad observed in his presentation.
Because GDMT is similarly “uncommon” among patients hospitalized with acute HF, the team designed the current trial, a test of the hypothesis that a similar system of nudges would lead to higher rates of prescriptions of the four core GDMT drug classes.
The study enrolled 920 adults with acute HF, an EF of 40% or lower (their median was 28%), and NT-proBNP levels higher than 500 pg/mL. The patients received IV diuretics for the first 24 in-hospital hours and were not taking medications from any of the four core HF drug classes. Their mean age was 74, 36% were women, and 25% were Black.
Physicians of patients who were randomly assigned to the intervention received the alerts as they entered information that involved ejection fraction, blood pressure, potassium levels, heart rate, glomerular filtration rate, and meds they were currently or should be taking, “along with an order set that made ordering those medications very easy,” Dr. Ahmad said.
“There was absolutely no evidence that the alert made any difference. There were zero patients on all four classes of GDMT at baseline, and at the time of discharge, only 11.2% of patients were on all four pillars – essentially, one in nine patients,” Dr. Ahmad said. Nor were there any subgroup differences in age, sex, race, ejection fraction, type of health insurance, or whether care was provided by a cardiologist or noncardiologist physician.
The study was limited by having been conducted within a single health care network using only the Epic EHR system. The alerts did not go exclusively to cardiologists, and patient preferences were not considered in the analysis. Also, the study’s alerts represented only some of the many that were received by the clinicians during the course of the trial.
Better incentives needed
“We believe this shows that refinement of the nudges is needed, as well as changes to clinician incentives to overcome barriers to implementation of GDMT during hospitalizations for AHF,” Dr. Ahmad said.
Responding to a postpresentation question on whether the postdischarge phase might be a more effective time to intervene with nudges, Dr. Ahmad observed that many clinicians who care for patients in the hospital assume that someone else will have the patient receive appropriate meds after discharge. “But we know that things that are started in the hospital tend to stick better.
“I do think that a lot of the clinicians were thinking, ‘I’m just going to get this patient out and someone in the outside will get them on GDMT,’ ” he said.
In the United States there are many incentives to reduce hospital length of stay and to expedite discharge so more beds are available for incoming patients, Dr. Ahmad observed. “I think it’s a combination of these kinds of perverse incentives that are not allowing us to get patients on appropriate GDMT during hospitalization.”
Furthermore, Dr. Ahmad told this news organization, “additions to the EHR should be evaluated in an evidence-based manner. However, the opposite has occurred, with an unregulated data tsunami crushing clinicians, which has been bad both for the clinicians and for patients.”
The study was funded by AstraZeneca. Dr. Ahmad discloses receiving research funding from and consulting for AstraZeneca; and receiving research funding from Boehringer Ingelheim, Cytokinetics, and Relypsa. Three other coauthors are employees of AstraZeneca.
A version of this article first appeared on Medscape.com.
in a randomized trial conducted at several centers in the same health care system.
The results of the PROMPT-AHF trial, which assigned such patients to have or not have the GDMT-promoting physician nudges as part of their in-hospital management, were “not entirely surprising,” Tariq Ahmad, MD, MPH, of Yale University, New Haven, Conn., said in an interview.
“We have created an environment in the hospital that makes care quite fractured for patients with heart failure,” he said. “They are cared for by many different clinicians, which leads to well-known behaviors such as diffusion of responsibility.”
Moreover, many clinicians focus on stabilizing patients “rather than starting them on a comprehensive set of medications, which most think should be done after discharge,” Dr. Ahmad added.
“Importantly, there has been a logarithmic increase in alerts while patients are hospitalized that has caused clinician burnout and is leading to even very important alerts being ignored.”
Likely as a result, the trial saw no significant difference between the alert and no-alert groups in how often the number of GDMT prescriptions rose by at least one drug class, whether beta blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, or SGLT2 inhibitors. That happened for 34% of patients in both groups, reported Dr. Ahmad at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions
Nor was there a difference in the secondary endpoint of increased number of GDMT meds or escalated dosage of prescribed GDMT drugs.
GDMT ‘uncommon’ in AHF
In an earlier trial in outpatients with chronic HF, conducted by many of the same researchers, use of a targeted EHR-based alert system was associated with significantly higher rates of GDMT prescriptions 30 days after discharge, compared with usual care, Dr. Ahmad observed in his presentation.
Because GDMT is similarly “uncommon” among patients hospitalized with acute HF, the team designed the current trial, a test of the hypothesis that a similar system of nudges would lead to higher rates of prescriptions of the four core GDMT drug classes.
The study enrolled 920 adults with acute HF, an EF of 40% or lower (their median was 28%), and NT-proBNP levels higher than 500 pg/mL. The patients received IV diuretics for the first 24 in-hospital hours and were not taking medications from any of the four core HF drug classes. Their mean age was 74, 36% were women, and 25% were Black.
Physicians of patients who were randomly assigned to the intervention received the alerts as they entered information that involved ejection fraction, blood pressure, potassium levels, heart rate, glomerular filtration rate, and meds they were currently or should be taking, “along with an order set that made ordering those medications very easy,” Dr. Ahmad said.
“There was absolutely no evidence that the alert made any difference. There were zero patients on all four classes of GDMT at baseline, and at the time of discharge, only 11.2% of patients were on all four pillars – essentially, one in nine patients,” Dr. Ahmad said. Nor were there any subgroup differences in age, sex, race, ejection fraction, type of health insurance, or whether care was provided by a cardiologist or noncardiologist physician.
The study was limited by having been conducted within a single health care network using only the Epic EHR system. The alerts did not go exclusively to cardiologists, and patient preferences were not considered in the analysis. Also, the study’s alerts represented only some of the many that were received by the clinicians during the course of the trial.
Better incentives needed
“We believe this shows that refinement of the nudges is needed, as well as changes to clinician incentives to overcome barriers to implementation of GDMT during hospitalizations for AHF,” Dr. Ahmad said.
Responding to a postpresentation question on whether the postdischarge phase might be a more effective time to intervene with nudges, Dr. Ahmad observed that many clinicians who care for patients in the hospital assume that someone else will have the patient receive appropriate meds after discharge. “But we know that things that are started in the hospital tend to stick better.
“I do think that a lot of the clinicians were thinking, ‘I’m just going to get this patient out and someone in the outside will get them on GDMT,’ ” he said.
In the United States there are many incentives to reduce hospital length of stay and to expedite discharge so more beds are available for incoming patients, Dr. Ahmad observed. “I think it’s a combination of these kinds of perverse incentives that are not allowing us to get patients on appropriate GDMT during hospitalization.”
Furthermore, Dr. Ahmad told this news organization, “additions to the EHR should be evaluated in an evidence-based manner. However, the opposite has occurred, with an unregulated data tsunami crushing clinicians, which has been bad both for the clinicians and for patients.”
The study was funded by AstraZeneca. Dr. Ahmad discloses receiving research funding from and consulting for AstraZeneca; and receiving research funding from Boehringer Ingelheim, Cytokinetics, and Relypsa. Three other coauthors are employees of AstraZeneca.
A version of this article first appeared on Medscape.com.
in a randomized trial conducted at several centers in the same health care system.
The results of the PROMPT-AHF trial, which assigned such patients to have or not have the GDMT-promoting physician nudges as part of their in-hospital management, were “not entirely surprising,” Tariq Ahmad, MD, MPH, of Yale University, New Haven, Conn., said in an interview.
“We have created an environment in the hospital that makes care quite fractured for patients with heart failure,” he said. “They are cared for by many different clinicians, which leads to well-known behaviors such as diffusion of responsibility.”
Moreover, many clinicians focus on stabilizing patients “rather than starting them on a comprehensive set of medications, which most think should be done after discharge,” Dr. Ahmad added.
“Importantly, there has been a logarithmic increase in alerts while patients are hospitalized that has caused clinician burnout and is leading to even very important alerts being ignored.”
Likely as a result, the trial saw no significant difference between the alert and no-alert groups in how often the number of GDMT prescriptions rose by at least one drug class, whether beta blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, or SGLT2 inhibitors. That happened for 34% of patients in both groups, reported Dr. Ahmad at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions
Nor was there a difference in the secondary endpoint of increased number of GDMT meds or escalated dosage of prescribed GDMT drugs.
GDMT ‘uncommon’ in AHF
In an earlier trial in outpatients with chronic HF, conducted by many of the same researchers, use of a targeted EHR-based alert system was associated with significantly higher rates of GDMT prescriptions 30 days after discharge, compared with usual care, Dr. Ahmad observed in his presentation.
Because GDMT is similarly “uncommon” among patients hospitalized with acute HF, the team designed the current trial, a test of the hypothesis that a similar system of nudges would lead to higher rates of prescriptions of the four core GDMT drug classes.
The study enrolled 920 adults with acute HF, an EF of 40% or lower (their median was 28%), and NT-proBNP levels higher than 500 pg/mL. The patients received IV diuretics for the first 24 in-hospital hours and were not taking medications from any of the four core HF drug classes. Their mean age was 74, 36% were women, and 25% were Black.
Physicians of patients who were randomly assigned to the intervention received the alerts as they entered information that involved ejection fraction, blood pressure, potassium levels, heart rate, glomerular filtration rate, and meds they were currently or should be taking, “along with an order set that made ordering those medications very easy,” Dr. Ahmad said.
“There was absolutely no evidence that the alert made any difference. There were zero patients on all four classes of GDMT at baseline, and at the time of discharge, only 11.2% of patients were on all four pillars – essentially, one in nine patients,” Dr. Ahmad said. Nor were there any subgroup differences in age, sex, race, ejection fraction, type of health insurance, or whether care was provided by a cardiologist or noncardiologist physician.
The study was limited by having been conducted within a single health care network using only the Epic EHR system. The alerts did not go exclusively to cardiologists, and patient preferences were not considered in the analysis. Also, the study’s alerts represented only some of the many that were received by the clinicians during the course of the trial.
Better incentives needed
“We believe this shows that refinement of the nudges is needed, as well as changes to clinician incentives to overcome barriers to implementation of GDMT during hospitalizations for AHF,” Dr. Ahmad said.
Responding to a postpresentation question on whether the postdischarge phase might be a more effective time to intervene with nudges, Dr. Ahmad observed that many clinicians who care for patients in the hospital assume that someone else will have the patient receive appropriate meds after discharge. “But we know that things that are started in the hospital tend to stick better.
“I do think that a lot of the clinicians were thinking, ‘I’m just going to get this patient out and someone in the outside will get them on GDMT,’ ” he said.
In the United States there are many incentives to reduce hospital length of stay and to expedite discharge so more beds are available for incoming patients, Dr. Ahmad observed. “I think it’s a combination of these kinds of perverse incentives that are not allowing us to get patients on appropriate GDMT during hospitalization.”
Furthermore, Dr. Ahmad told this news organization, “additions to the EHR should be evaluated in an evidence-based manner. However, the opposite has occurred, with an unregulated data tsunami crushing clinicians, which has been bad both for the clinicians and for patients.”
The study was funded by AstraZeneca. Dr. Ahmad discloses receiving research funding from and consulting for AstraZeneca; and receiving research funding from Boehringer Ingelheim, Cytokinetics, and Relypsa. Three other coauthors are employees of AstraZeneca.
A version of this article first appeared on Medscape.com.
FROM ESC Heart Failure 2023
ARNI bests ARB to reduce NT-proBNP in stabilized preserved-EF HF
Patients with an ejection fraction (EF) greater than 40% who were stabilized after recent worsening or de novo heart failure (HF) had a greater reduction in natriuretic peptides and less worsening renal function, but a higher rate of hypotension over 8 weeks with sacubitril-valsartan (Entresto) versus valsartan (Diovan) in the PARAGLIDE-HF trial.
A subgroup analysis showed evidence of a larger treatment effect among those with an EF of 60% or less, said Robert Mentz, MD, of the Duke Clinical Research Institute, Durham, N.C.
Dr. Mentz presented the findings at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) scientific sessions. The study was also published online simultaneously in the Journal of the American College of Cardiology.
“Next steps will involve further assessment of the cardiovascular and renal benefits, as well as further exploration of the symptomatic hypotension that we observed,” Dr. Mentz said in an interview.
Meanwhile, he said, “clinicians should be aware of these new data – specifically, the incremental reduction in natriuretic peptide level, compared with valsartan, and potential benefits on cardiovascular and renal events,” particularly in those with an EF greater than 40% to 60% or less.
Larger benefit for EF > 40% to < 60%
PARAGLIDE-HF was a double-blind, randomized controlled trial with 466 patients with EF greater than 40% enrolled within 30 days of a worsening HF event. The median age was 71 years, 52% were women, and 22% were Black.
The trial was a follow-up to PARAGON-HF, which had shown that, in patients with an EF of at least 45%, sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for HF or death from cardiovascular causes, compared with valsartan.
The primary endpoint for PARAGLIDE was the time-averaged proportional change in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8, as in the PIONEER-HF trial. That trial showed that among patients hospitalized for acute decompensated HF with reduced EF (< 40%), the angiotensin receptor/neprilysin inhibitor (ARNI) led to a greater reduction in NT-proBNP concentration than the angiotensin receptor blocker (ARB).
Similarly, for PARAGLIDE, the time-averaged reduction in NT-proBNP was greater with sacubitril-valsartan, with a change ratio of 0.85 (15% greater reduction).
A secondary hierarchical outcome for PARAGLIDE, using the win ratio, consisted of time to cardiovascular death, number and timing of HF hospitalizations, number and timing of urgent HF visits, and time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8.
The hierarchical outcome favored sacubitril-valsartan, but was not significant (unmatched win ratio, 1.19).
As noted, sacubitril-valsartan reduced worsening renal function, compared with valsartan (odds ratio, 0.61), but increased symptomatic hypotension (OR, 1.73).
“We will work to better characterize the hypotension events that were observed to help identify those patients at greater risk and to provide further clarity around the timing and implications of these events,” Dr. Mentz said in an interview.
The team hypothesized that such events may be prevented by optimizing volume status and background therapies commonly used to treat hypertension in these patients.
“For instance,” Dr. Mentz suggested, “calcium channel blockers like amlodipine could be dose reduced or discontinued in patients with lower baseline blood pressures to better support sacubitril/valsartan initiation and titration.”
He highlighted the subgroup analysis showing evidence of a larger treatment effect in study patients with an EF of 60% or less for the NT-proBNP change (0.78) and the hierarchical outcome (win ratio, 1.46).
“These data may influence future guidance for sacubitril-valsartan in HF with EF greater than 40%, regardless of HF chronicity [acute or chronic vs. de novo] and treatment setting [hospital vs. clinic],” Dr. Mentz concluded.
Data ‘far from conclusive’
In a comment, Sean Pinney, MD, chief of cardiology at Mount Sinai Morningside, New York, said that the study results “help expand the current evidence base supporting the use of an ARNI in patients” with an EF greater than 40% up to 60%, and “provide confidence that ARNIs help to lower natriuretic peptides.
“It comes as little surprise that not everyone was able to tolerate these medications due to intolerable side effects like dizziness or hypotension,” he said.
Nevertheless, he added, “hopefully, these trial data help strengthen clinicians’ resolve to prescribe sacubitril/valsartan to a growing population of vulnerable patients.”
In a related editorial, Hector O. Ventura, MD, of the Ochsner Clinical School–University of Queensland, New Orleans, and colleagues express several concerns about the study.
Although the trial achieved significance for the primary endpoint, the margin of benefit was less than expected and the magnitude of the NT-proBNP reduction may not have been enough to reach the threshold for clinical benefit, they wrote.
Diuretic dosing in the two groups was not reported, and between-group differences may have contributed to both the differential NT-proBNP reduction and the rates of hypotension.
Furthermore, the sacubitril-valsartan group had a higher proportion of missing NT-proBNP data, which may have biased the results.
“Clinicians who elect to use sacubitril-valsartan in this population should be mindful of the risk for hypotension and select patients carefully, while providing close ambulatory follow up to ensure stability and adherence,” they noted.
“This important trial provides some wins that support selective use of sacubitril-valsartan in HFpEF [as well as] observed losses, which too may help to define better implementation strategies in appropriately selected patients,” the editorialists concluded.
The study was funded by Novartis. Dr. Mentz and other coauthors have received fees from Novartis. Dr. Pinney, Dr. Ventura, and the other editorialists disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with an ejection fraction (EF) greater than 40% who were stabilized after recent worsening or de novo heart failure (HF) had a greater reduction in natriuretic peptides and less worsening renal function, but a higher rate of hypotension over 8 weeks with sacubitril-valsartan (Entresto) versus valsartan (Diovan) in the PARAGLIDE-HF trial.
A subgroup analysis showed evidence of a larger treatment effect among those with an EF of 60% or less, said Robert Mentz, MD, of the Duke Clinical Research Institute, Durham, N.C.
Dr. Mentz presented the findings at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) scientific sessions. The study was also published online simultaneously in the Journal of the American College of Cardiology.
“Next steps will involve further assessment of the cardiovascular and renal benefits, as well as further exploration of the symptomatic hypotension that we observed,” Dr. Mentz said in an interview.
Meanwhile, he said, “clinicians should be aware of these new data – specifically, the incremental reduction in natriuretic peptide level, compared with valsartan, and potential benefits on cardiovascular and renal events,” particularly in those with an EF greater than 40% to 60% or less.
Larger benefit for EF > 40% to < 60%
PARAGLIDE-HF was a double-blind, randomized controlled trial with 466 patients with EF greater than 40% enrolled within 30 days of a worsening HF event. The median age was 71 years, 52% were women, and 22% were Black.
The trial was a follow-up to PARAGON-HF, which had shown that, in patients with an EF of at least 45%, sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for HF or death from cardiovascular causes, compared with valsartan.
The primary endpoint for PARAGLIDE was the time-averaged proportional change in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8, as in the PIONEER-HF trial. That trial showed that among patients hospitalized for acute decompensated HF with reduced EF (< 40%), the angiotensin receptor/neprilysin inhibitor (ARNI) led to a greater reduction in NT-proBNP concentration than the angiotensin receptor blocker (ARB).
Similarly, for PARAGLIDE, the time-averaged reduction in NT-proBNP was greater with sacubitril-valsartan, with a change ratio of 0.85 (15% greater reduction).
A secondary hierarchical outcome for PARAGLIDE, using the win ratio, consisted of time to cardiovascular death, number and timing of HF hospitalizations, number and timing of urgent HF visits, and time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8.
The hierarchical outcome favored sacubitril-valsartan, but was not significant (unmatched win ratio, 1.19).
As noted, sacubitril-valsartan reduced worsening renal function, compared with valsartan (odds ratio, 0.61), but increased symptomatic hypotension (OR, 1.73).
“We will work to better characterize the hypotension events that were observed to help identify those patients at greater risk and to provide further clarity around the timing and implications of these events,” Dr. Mentz said in an interview.
The team hypothesized that such events may be prevented by optimizing volume status and background therapies commonly used to treat hypertension in these patients.
“For instance,” Dr. Mentz suggested, “calcium channel blockers like amlodipine could be dose reduced or discontinued in patients with lower baseline blood pressures to better support sacubitril/valsartan initiation and titration.”
He highlighted the subgroup analysis showing evidence of a larger treatment effect in study patients with an EF of 60% or less for the NT-proBNP change (0.78) and the hierarchical outcome (win ratio, 1.46).
“These data may influence future guidance for sacubitril-valsartan in HF with EF greater than 40%, regardless of HF chronicity [acute or chronic vs. de novo] and treatment setting [hospital vs. clinic],” Dr. Mentz concluded.
Data ‘far from conclusive’
In a comment, Sean Pinney, MD, chief of cardiology at Mount Sinai Morningside, New York, said that the study results “help expand the current evidence base supporting the use of an ARNI in patients” with an EF greater than 40% up to 60%, and “provide confidence that ARNIs help to lower natriuretic peptides.
“It comes as little surprise that not everyone was able to tolerate these medications due to intolerable side effects like dizziness or hypotension,” he said.
Nevertheless, he added, “hopefully, these trial data help strengthen clinicians’ resolve to prescribe sacubitril/valsartan to a growing population of vulnerable patients.”
In a related editorial, Hector O. Ventura, MD, of the Ochsner Clinical School–University of Queensland, New Orleans, and colleagues express several concerns about the study.
Although the trial achieved significance for the primary endpoint, the margin of benefit was less than expected and the magnitude of the NT-proBNP reduction may not have been enough to reach the threshold for clinical benefit, they wrote.
Diuretic dosing in the two groups was not reported, and between-group differences may have contributed to both the differential NT-proBNP reduction and the rates of hypotension.
Furthermore, the sacubitril-valsartan group had a higher proportion of missing NT-proBNP data, which may have biased the results.
“Clinicians who elect to use sacubitril-valsartan in this population should be mindful of the risk for hypotension and select patients carefully, while providing close ambulatory follow up to ensure stability and adherence,” they noted.
“This important trial provides some wins that support selective use of sacubitril-valsartan in HFpEF [as well as] observed losses, which too may help to define better implementation strategies in appropriately selected patients,” the editorialists concluded.
The study was funded by Novartis. Dr. Mentz and other coauthors have received fees from Novartis. Dr. Pinney, Dr. Ventura, and the other editorialists disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with an ejection fraction (EF) greater than 40% who were stabilized after recent worsening or de novo heart failure (HF) had a greater reduction in natriuretic peptides and less worsening renal function, but a higher rate of hypotension over 8 weeks with sacubitril-valsartan (Entresto) versus valsartan (Diovan) in the PARAGLIDE-HF trial.
A subgroup analysis showed evidence of a larger treatment effect among those with an EF of 60% or less, said Robert Mentz, MD, of the Duke Clinical Research Institute, Durham, N.C.
Dr. Mentz presented the findings at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) scientific sessions. The study was also published online simultaneously in the Journal of the American College of Cardiology.
“Next steps will involve further assessment of the cardiovascular and renal benefits, as well as further exploration of the symptomatic hypotension that we observed,” Dr. Mentz said in an interview.
Meanwhile, he said, “clinicians should be aware of these new data – specifically, the incremental reduction in natriuretic peptide level, compared with valsartan, and potential benefits on cardiovascular and renal events,” particularly in those with an EF greater than 40% to 60% or less.
Larger benefit for EF > 40% to < 60%
PARAGLIDE-HF was a double-blind, randomized controlled trial with 466 patients with EF greater than 40% enrolled within 30 days of a worsening HF event. The median age was 71 years, 52% were women, and 22% were Black.
The trial was a follow-up to PARAGON-HF, which had shown that, in patients with an EF of at least 45%, sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for HF or death from cardiovascular causes, compared with valsartan.
The primary endpoint for PARAGLIDE was the time-averaged proportional change in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8, as in the PIONEER-HF trial. That trial showed that among patients hospitalized for acute decompensated HF with reduced EF (< 40%), the angiotensin receptor/neprilysin inhibitor (ARNI) led to a greater reduction in NT-proBNP concentration than the angiotensin receptor blocker (ARB).
Similarly, for PARAGLIDE, the time-averaged reduction in NT-proBNP was greater with sacubitril-valsartan, with a change ratio of 0.85 (15% greater reduction).
A secondary hierarchical outcome for PARAGLIDE, using the win ratio, consisted of time to cardiovascular death, number and timing of HF hospitalizations, number and timing of urgent HF visits, and time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8.
The hierarchical outcome favored sacubitril-valsartan, but was not significant (unmatched win ratio, 1.19).
As noted, sacubitril-valsartan reduced worsening renal function, compared with valsartan (odds ratio, 0.61), but increased symptomatic hypotension (OR, 1.73).
“We will work to better characterize the hypotension events that were observed to help identify those patients at greater risk and to provide further clarity around the timing and implications of these events,” Dr. Mentz said in an interview.
The team hypothesized that such events may be prevented by optimizing volume status and background therapies commonly used to treat hypertension in these patients.
“For instance,” Dr. Mentz suggested, “calcium channel blockers like amlodipine could be dose reduced or discontinued in patients with lower baseline blood pressures to better support sacubitril/valsartan initiation and titration.”
He highlighted the subgroup analysis showing evidence of a larger treatment effect in study patients with an EF of 60% or less for the NT-proBNP change (0.78) and the hierarchical outcome (win ratio, 1.46).
“These data may influence future guidance for sacubitril-valsartan in HF with EF greater than 40%, regardless of HF chronicity [acute or chronic vs. de novo] and treatment setting [hospital vs. clinic],” Dr. Mentz concluded.
Data ‘far from conclusive’
In a comment, Sean Pinney, MD, chief of cardiology at Mount Sinai Morningside, New York, said that the study results “help expand the current evidence base supporting the use of an ARNI in patients” with an EF greater than 40% up to 60%, and “provide confidence that ARNIs help to lower natriuretic peptides.
“It comes as little surprise that not everyone was able to tolerate these medications due to intolerable side effects like dizziness or hypotension,” he said.
Nevertheless, he added, “hopefully, these trial data help strengthen clinicians’ resolve to prescribe sacubitril/valsartan to a growing population of vulnerable patients.”
In a related editorial, Hector O. Ventura, MD, of the Ochsner Clinical School–University of Queensland, New Orleans, and colleagues express several concerns about the study.
Although the trial achieved significance for the primary endpoint, the margin of benefit was less than expected and the magnitude of the NT-proBNP reduction may not have been enough to reach the threshold for clinical benefit, they wrote.
Diuretic dosing in the two groups was not reported, and between-group differences may have contributed to both the differential NT-proBNP reduction and the rates of hypotension.
Furthermore, the sacubitril-valsartan group had a higher proportion of missing NT-proBNP data, which may have biased the results.
“Clinicians who elect to use sacubitril-valsartan in this population should be mindful of the risk for hypotension and select patients carefully, while providing close ambulatory follow up to ensure stability and adherence,” they noted.
“This important trial provides some wins that support selective use of sacubitril-valsartan in HFpEF [as well as] observed losses, which too may help to define better implementation strategies in appropriately selected patients,” the editorialists concluded.
The study was funded by Novartis. Dr. Mentz and other coauthors have received fees from Novartis. Dr. Pinney, Dr. Ventura, and the other editorialists disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ESC HEART FAILURE 2023
Trientine reduces NT-proBNP up to 8 weeks in HFrEF: TRACER-HF
In models of HF, intracellular copper depletion is associated with myocardial hypertrophy and fibrosis, and thus an increased risk for cardiac remodeling, James Januzzi, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, told attendees at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions.
Although trientine has been used for over 40 years to treat Wilson disease – a rare inherited disease characterized by copper overload – “paradoxically, it acts as a copper chaperone and can restore intracellular copper concentrations at low doses,” Dr. Januzzi explained during his presentation of the TRACER-HF results.
Although the dose-ranging study found that at 300 mg twice daily trientine effectively reduced NT-proBNP levels at 4 and 8 weeks, by 12 weeks, the effect had disappeared.
Nevertheless, Dr. Januzzi told the meeting attendees that the same dose was “most consistently” associated with most favorable Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) changes, as well as improvements in left ventricular (LV) function and 6-minute walk distance.
‘Challenging is an understatement’
Asked why the improvement in NT-proBNP levels was no longer evident at week 12, Dr. Januzzi acknowledged, “We just don’t know.” However, the team speculates that the disrupted nature of the study might play a role.
The phase 2, placebo-controlled trial started recruiting at 27 sites in North America in 2019. When the pandemic hit in 2020, enrollment was suspended, then pivoted to China in 2021. A total of 190 participants were ultimately enrolled.
However, 91% of participants in China were finishing their follow-up in late 2022, when the country was hit by a COVID-19 surge, which might have affected the 12-week outcomes – though this is speculation for now.
Overall, participants had a mean age of 57 years; about 80% were men; 91% were Asian; the mean left ventricular ejection fraction (LVEF) was 30%; and most (77%) were New York Heart Association class II. All were stable on optimal drug therapy, including chronic loop diuretics.
All had elevated NT-proBNP: ≥ 400 pg/mL without atrial fibrillation or flutter, or ≥ 1200 pg/mL with atrial fibrillation or flutter.
Participants were randomized to placebo or twice-daily trientine doses of 50 mg, 150 mg, or 300 mg.
The primary endpoint was the proportional change in NT-proBNP from baseline to 12 weeks. Key secondary endpoints included the effect of trientine compared with placebo on mechanistic outcomes such as change in cardiac remodeling indices, 6-minute walk distance, and the KCCQ-OSS.
As noted, the greatest reduction in NT-proBNP at 4 and 8 weeks was in the 300-mg group, with a geometric mean ratio of 0.82 at week 4 vs. 1.03 for placebo; 0.92 for 50 mg; and 0.83 for 150 mg; and 0.79 at week 8 vs 1.02 for placebo; 0.85 for 50 mg; and 0.91 for 150 mg.
LV volumes improved at all doses, though by the most at 50 mg (–11.7 mL).
The change in 6-minute walk distance was greatest at the 300-mg dose at 42 meters.
The responder analysis showed that 300 mg was most consistently associated with most of the favorable KCCQ changes.
From a safety standpoint, trientine was well tolerated without any adverse outcomes. Notably, Dr. Januzzi told meeting attendees, blood pressure and heart rate were not affected by the addition of trientine to background medical care.
In addition, a post hoc interaction was identified between treatment response and a baseline LVEF ≤ 30%, data that, for now, are “compelling but hypothesis-generating,” he said. Data on secondary endpoints specifically for that group “are forthcoming.”
Looking ahead
Dr. Januzzi said in an interview that the team is now finalizing the main report “and will turn our attention to the interaction analyses suggesting exaggerated benefit in those with lower LVEF.
“We are examining all possible options for this novel therapy, which may include progressing to phase 3,” he said.
Challenges going forward include the need to understand which patients are most appropriate for the drug. “Given that it does not affect blood pressure or heart rate, it is an attractive consideration for any patient on guideline-directed medical therapy, but we need to have more clarity about the mechanism of benefit and understanding about the subgroup interactions that we have detected.
“Even in a well-managed population of patients with heart failure, there may still be room for therapies with benefit,” he concluded.
Danyaal Moin, MD, assistant professor of medicine at NYU Langone Health in New York and a specialist in advanced heart failure and transplantation, commented on these findings for this article.
“It is always exciting to consider new pathways to treat patients with systolic dysfunction, given the residual risk even for patients on contemporary quadruple therapy for HFrEF,” he said. “However, certain challenges with this phase 2 study will need to be addressed in an eventual phase 3 clinical trial.
“The study sample was predominately recruited in China and is not necessarily representative of a heart failure population in many clinical practices,” he said.
“It would be important that future studies with trientine-HCL assess endpoints such as heart failure hospitalizations and mortality that would help elucidate where this therapy would stand relative to current established heart failure therapies.”
Longer follow-up is needed and, he noted, “while it appears the investigators will ultimately favor the 300-mg dosage, it is interesting that left ventricular volume indices changed most favorably with the 50-mg dose of the therapy.”
The study was sponsored by Innolife Pharmaceuticals and coordinated by the Baim Institute for Clinical Research in Boston. Dr. Januzzi has received grant support from Innolife. Dr. Moin declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In models of HF, intracellular copper depletion is associated with myocardial hypertrophy and fibrosis, and thus an increased risk for cardiac remodeling, James Januzzi, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, told attendees at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions.
Although trientine has been used for over 40 years to treat Wilson disease – a rare inherited disease characterized by copper overload – “paradoxically, it acts as a copper chaperone and can restore intracellular copper concentrations at low doses,” Dr. Januzzi explained during his presentation of the TRACER-HF results.
Although the dose-ranging study found that at 300 mg twice daily trientine effectively reduced NT-proBNP levels at 4 and 8 weeks, by 12 weeks, the effect had disappeared.
Nevertheless, Dr. Januzzi told the meeting attendees that the same dose was “most consistently” associated with most favorable Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) changes, as well as improvements in left ventricular (LV) function and 6-minute walk distance.
‘Challenging is an understatement’
Asked why the improvement in NT-proBNP levels was no longer evident at week 12, Dr. Januzzi acknowledged, “We just don’t know.” However, the team speculates that the disrupted nature of the study might play a role.
The phase 2, placebo-controlled trial started recruiting at 27 sites in North America in 2019. When the pandemic hit in 2020, enrollment was suspended, then pivoted to China in 2021. A total of 190 participants were ultimately enrolled.
However, 91% of participants in China were finishing their follow-up in late 2022, when the country was hit by a COVID-19 surge, which might have affected the 12-week outcomes – though this is speculation for now.
Overall, participants had a mean age of 57 years; about 80% were men; 91% were Asian; the mean left ventricular ejection fraction (LVEF) was 30%; and most (77%) were New York Heart Association class II. All were stable on optimal drug therapy, including chronic loop diuretics.
All had elevated NT-proBNP: ≥ 400 pg/mL without atrial fibrillation or flutter, or ≥ 1200 pg/mL with atrial fibrillation or flutter.
Participants were randomized to placebo or twice-daily trientine doses of 50 mg, 150 mg, or 300 mg.
The primary endpoint was the proportional change in NT-proBNP from baseline to 12 weeks. Key secondary endpoints included the effect of trientine compared with placebo on mechanistic outcomes such as change in cardiac remodeling indices, 6-minute walk distance, and the KCCQ-OSS.
As noted, the greatest reduction in NT-proBNP at 4 and 8 weeks was in the 300-mg group, with a geometric mean ratio of 0.82 at week 4 vs. 1.03 for placebo; 0.92 for 50 mg; and 0.83 for 150 mg; and 0.79 at week 8 vs 1.02 for placebo; 0.85 for 50 mg; and 0.91 for 150 mg.
LV volumes improved at all doses, though by the most at 50 mg (–11.7 mL).
The change in 6-minute walk distance was greatest at the 300-mg dose at 42 meters.
The responder analysis showed that 300 mg was most consistently associated with most of the favorable KCCQ changes.
From a safety standpoint, trientine was well tolerated without any adverse outcomes. Notably, Dr. Januzzi told meeting attendees, blood pressure and heart rate were not affected by the addition of trientine to background medical care.
In addition, a post hoc interaction was identified between treatment response and a baseline LVEF ≤ 30%, data that, for now, are “compelling but hypothesis-generating,” he said. Data on secondary endpoints specifically for that group “are forthcoming.”
Looking ahead
Dr. Januzzi said in an interview that the team is now finalizing the main report “and will turn our attention to the interaction analyses suggesting exaggerated benefit in those with lower LVEF.
“We are examining all possible options for this novel therapy, which may include progressing to phase 3,” he said.
Challenges going forward include the need to understand which patients are most appropriate for the drug. “Given that it does not affect blood pressure or heart rate, it is an attractive consideration for any patient on guideline-directed medical therapy, but we need to have more clarity about the mechanism of benefit and understanding about the subgroup interactions that we have detected.
“Even in a well-managed population of patients with heart failure, there may still be room for therapies with benefit,” he concluded.
Danyaal Moin, MD, assistant professor of medicine at NYU Langone Health in New York and a specialist in advanced heart failure and transplantation, commented on these findings for this article.
“It is always exciting to consider new pathways to treat patients with systolic dysfunction, given the residual risk even for patients on contemporary quadruple therapy for HFrEF,” he said. “However, certain challenges with this phase 2 study will need to be addressed in an eventual phase 3 clinical trial.
“The study sample was predominately recruited in China and is not necessarily representative of a heart failure population in many clinical practices,” he said.
“It would be important that future studies with trientine-HCL assess endpoints such as heart failure hospitalizations and mortality that would help elucidate where this therapy would stand relative to current established heart failure therapies.”
Longer follow-up is needed and, he noted, “while it appears the investigators will ultimately favor the 300-mg dosage, it is interesting that left ventricular volume indices changed most favorably with the 50-mg dose of the therapy.”
The study was sponsored by Innolife Pharmaceuticals and coordinated by the Baim Institute for Clinical Research in Boston. Dr. Januzzi has received grant support from Innolife. Dr. Moin declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In models of HF, intracellular copper depletion is associated with myocardial hypertrophy and fibrosis, and thus an increased risk for cardiac remodeling, James Januzzi, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, told attendees at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions.
Although trientine has been used for over 40 years to treat Wilson disease – a rare inherited disease characterized by copper overload – “paradoxically, it acts as a copper chaperone and can restore intracellular copper concentrations at low doses,” Dr. Januzzi explained during his presentation of the TRACER-HF results.
Although the dose-ranging study found that at 300 mg twice daily trientine effectively reduced NT-proBNP levels at 4 and 8 weeks, by 12 weeks, the effect had disappeared.
Nevertheless, Dr. Januzzi told the meeting attendees that the same dose was “most consistently” associated with most favorable Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) changes, as well as improvements in left ventricular (LV) function and 6-minute walk distance.
‘Challenging is an understatement’
Asked why the improvement in NT-proBNP levels was no longer evident at week 12, Dr. Januzzi acknowledged, “We just don’t know.” However, the team speculates that the disrupted nature of the study might play a role.
The phase 2, placebo-controlled trial started recruiting at 27 sites in North America in 2019. When the pandemic hit in 2020, enrollment was suspended, then pivoted to China in 2021. A total of 190 participants were ultimately enrolled.
However, 91% of participants in China were finishing their follow-up in late 2022, when the country was hit by a COVID-19 surge, which might have affected the 12-week outcomes – though this is speculation for now.
Overall, participants had a mean age of 57 years; about 80% were men; 91% were Asian; the mean left ventricular ejection fraction (LVEF) was 30%; and most (77%) were New York Heart Association class II. All were stable on optimal drug therapy, including chronic loop diuretics.
All had elevated NT-proBNP: ≥ 400 pg/mL without atrial fibrillation or flutter, or ≥ 1200 pg/mL with atrial fibrillation or flutter.
Participants were randomized to placebo or twice-daily trientine doses of 50 mg, 150 mg, or 300 mg.
The primary endpoint was the proportional change in NT-proBNP from baseline to 12 weeks. Key secondary endpoints included the effect of trientine compared with placebo on mechanistic outcomes such as change in cardiac remodeling indices, 6-minute walk distance, and the KCCQ-OSS.
As noted, the greatest reduction in NT-proBNP at 4 and 8 weeks was in the 300-mg group, with a geometric mean ratio of 0.82 at week 4 vs. 1.03 for placebo; 0.92 for 50 mg; and 0.83 for 150 mg; and 0.79 at week 8 vs 1.02 for placebo; 0.85 for 50 mg; and 0.91 for 150 mg.
LV volumes improved at all doses, though by the most at 50 mg (–11.7 mL).
The change in 6-minute walk distance was greatest at the 300-mg dose at 42 meters.
The responder analysis showed that 300 mg was most consistently associated with most of the favorable KCCQ changes.
From a safety standpoint, trientine was well tolerated without any adverse outcomes. Notably, Dr. Januzzi told meeting attendees, blood pressure and heart rate were not affected by the addition of trientine to background medical care.
In addition, a post hoc interaction was identified between treatment response and a baseline LVEF ≤ 30%, data that, for now, are “compelling but hypothesis-generating,” he said. Data on secondary endpoints specifically for that group “are forthcoming.”
Looking ahead
Dr. Januzzi said in an interview that the team is now finalizing the main report “and will turn our attention to the interaction analyses suggesting exaggerated benefit in those with lower LVEF.
“We are examining all possible options for this novel therapy, which may include progressing to phase 3,” he said.
Challenges going forward include the need to understand which patients are most appropriate for the drug. “Given that it does not affect blood pressure or heart rate, it is an attractive consideration for any patient on guideline-directed medical therapy, but we need to have more clarity about the mechanism of benefit and understanding about the subgroup interactions that we have detected.
“Even in a well-managed population of patients with heart failure, there may still be room for therapies with benefit,” he concluded.
Danyaal Moin, MD, assistant professor of medicine at NYU Langone Health in New York and a specialist in advanced heart failure and transplantation, commented on these findings for this article.
“It is always exciting to consider new pathways to treat patients with systolic dysfunction, given the residual risk even for patients on contemporary quadruple therapy for HFrEF,” he said. “However, certain challenges with this phase 2 study will need to be addressed in an eventual phase 3 clinical trial.
“The study sample was predominately recruited in China and is not necessarily representative of a heart failure population in many clinical practices,” he said.
“It would be important that future studies with trientine-HCL assess endpoints such as heart failure hospitalizations and mortality that would help elucidate where this therapy would stand relative to current established heart failure therapies.”
Longer follow-up is needed and, he noted, “while it appears the investigators will ultimately favor the 300-mg dosage, it is interesting that left ventricular volume indices changed most favorably with the 50-mg dose of the therapy.”
The study was sponsored by Innolife Pharmaceuticals and coordinated by the Baim Institute for Clinical Research in Boston. Dr. Januzzi has received grant support from Innolife. Dr. Moin declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ESC HEART FAILURE 2023
CardioMEMS boosts QoL, curbs HF hospitalizations: MONITOR-HF
In the first randomized clinical trial of remote pulmonary artery pressure–guided monitoring and management of chronic heart failure (HF) in Europe, the intervention “substantially” improved quality of life (QoL) and reduced HF hospitalizations, new data show.
The CardioMEMS-HF system (Abbot Laboratories) used in the trial, called MONITOR-HF, remotely monitors changes in pulmonary artery pressure and provides an early warning of worsening HF.
Jasper Brugts, MD, PhD, of Erasmus MC University Medical Centre, Rotterdam, the Netherlands, said in an interview, “The concordance on outcomes of the three CardioMEMS trials across different eras, evolving GDMT [guideline-directed medical therapy], different conditions (pandemic), and different health care systems is reassuring and supportive of technologies such as CardioMEMS to improve patient monitoring to prevent HF hospitalizations and improve QoL.”
Dr. Brugts presented the study at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions.
(11 vs. 17), in comparison with standard of care, Dr. Brugts told meeting attendees.
Furthermore, CardioMEMS monitors hypervolemia as well as hypovolemia, enabling “fine-tuning of diuretics.”
The presentation drew such applause that one chairperson described it as “close to a standing ovation.” The study was published simultaneously in The Lancet.
Aggregate evidence
Early clinical evidence of the benefits of remote monitoring with the CardioMEMS-HF system was provided by the CHAMPION trial, which included patients with New York Heart Association (NYHA) class III heart failure.
Results of the subsequent GUIDE-HF trial, which aimed to test a broader population of patients with NYHA class II–IV heart failure and either increased N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations or hospitalization, were inconclusive.
However, a pre–COVID-19 impact analysis of GUIDE-HF indicated a possible benefit, which was primarily driven by a lower HF hospitalization rate, compared with the control group. That finding was the basis for an expanded indication for the system from the U.S. Food and Drug Administration.
The 2022 FDA indication permits the use of CardioMEMS for patients with NYHA class II HF and for those with worsening HF, as assessed by elevated natriuretic peptide levels.
From United States to Europe
Aware that most CardioMEMS data came from U.S. trials, the investigators embarked on the current trial, MONITOR-HF, an open-label, randomized trial in 25 centers in the Netherlands. Eligible patients had chronic NYHA class III HF, irrespective of ejection fraction, and had previously undergone hospitalization for HF.
A total of 348 patients were randomly assigned to either CardioMEMS-HF or standard of care (SoC) between 2019 and 2022.The median age of the patients was 69 years, and the median ejection fraction was 30%.
All patients were scheduled to be seen by their clinician at 3 months, 6 months, and every 6 months thereafter for up to 48 months.
The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score at 12 months
That difference between groups was 7.13 (+7.05 in the CardioMEMS group and –0.08 in the SoC group).
In the responder analysis, the odds ratio of an improvement of at least 5 points in the KCCQ overall summary score was 1.69 in the CardioMEMS group vs. the SoC group; the OR of a deterioration of at least 5 points was 0.45.
Subgroup analyses showed no relevant heterogeneity in the treatment effect on total HF hospitalizations and, notably, no significant interaction in patients with an EF below 40% and an EF above 40%.
There was a significant reduction in the median NT-proBNP change from baseline only in the remote monitoring group (800 pg/mL) and a smaller, nonsignificant difference with SoC.
Both groups received highly appropriate background guideline–directed medical therapy throughout the study. There were no significant between-group differences at 12 months.
Freedom from device-related or system-related complications and sensor failure were 97.7% and 98.8%, respectively.
Two sensor failures occurred during a mean follow-up 1.8 years. The percentage of failures was comparable to CHAMPION and GUIDE-HF trials.
The trial was not powered to assess a mortality benefit.
Pick the right patients
“As in the U.S. trials, there will be side effects, so select the right patients, because [remote monitoring] is not without risk,” Dr. Brugts told meeting attendees.
That point also was made by Christiane E. Angermann of University and University Hospital Würzburg, Germany, in a related editorial in The Lancet.
“To reproduce these results on a large scale in real-life health care, diligent patient selection should identify those at high risk of heart failure–related hospitalization who agree with the concept of daily data collection and are able and motivated to comply with treatment recommendations even if asymptomatic,” Dr. Angermann writes.
“Without direct interaction between health care providers and patients, and timely treatment modification triggered by abnormal monitoring results, the care cycle might break and the potential benefits from early detection of decompensation would be lost.”
Val Rakita, MD, assistant professor of medicine at Temple University, Philadelphia, a specialist in advanced heart failure and main implanter of the CardioMEMS device at Temple University Hospital, commented on the study for this article.
“This study confirms the previous data that the device is very safe and effective in preventing HF hospitalizations and improving patients’ quality of life, even in a different population with more modern background guideline-directed medical therapy.”
Nevertheless, he noted, “Studies have yet to confirm a mortality benefit, despite logic telling us that preventing heart failure hospitalizations should also improve patient survival. More studies are needed to see if a survival benefit can be proven over a longer follow-up period.”
Overall, he said, “Remote monitoring allows more precise management of medications, prevention of hospitalizations, and improvement in quality of life, and I am an advocate for it in my practice.”
Not everyone is an advocate, however. In a commentary published last year, John M. Mandrola, MD, a cardiac electrophysiologist at Baptist Medical Associates in Louisville, Ky., said the expanded FDA indication for the device is the result of “dubious trial analysis, spin, lax regulation, and the growth of low-value care.”
Others also have questioned the device’s value in the clinic.
But at least for now, as Dr. Angermann writes, “Scientific evidence supports the use of the CardioMEMS-HF system to enhance remote patient management in heart failure care. For more widespread application, technological advancements are desirable to provide more comfort for patients and reusable external device components, thereby improving care experience and saving resources.”
The MONITOR-HF trial is funded by the Dutch Ministry of Health and Health Care institute. Dr. Brugts has an independent research grant from Abbott (investigator-sponsored study) and has had speaker engagements or has participated in advisory boards for Abbott and other pharmaceutical companies. Dr. Angermann has received personal fees from Abbott for serving as chair of the steering committee for the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) and consulting fees, honoraria, and travel costs from Abbott. Dr. Rakita has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the first randomized clinical trial of remote pulmonary artery pressure–guided monitoring and management of chronic heart failure (HF) in Europe, the intervention “substantially” improved quality of life (QoL) and reduced HF hospitalizations, new data show.
The CardioMEMS-HF system (Abbot Laboratories) used in the trial, called MONITOR-HF, remotely monitors changes in pulmonary artery pressure and provides an early warning of worsening HF.
Jasper Brugts, MD, PhD, of Erasmus MC University Medical Centre, Rotterdam, the Netherlands, said in an interview, “The concordance on outcomes of the three CardioMEMS trials across different eras, evolving GDMT [guideline-directed medical therapy], different conditions (pandemic), and different health care systems is reassuring and supportive of technologies such as CardioMEMS to improve patient monitoring to prevent HF hospitalizations and improve QoL.”
Dr. Brugts presented the study at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions.
(11 vs. 17), in comparison with standard of care, Dr. Brugts told meeting attendees.
Furthermore, CardioMEMS monitors hypervolemia as well as hypovolemia, enabling “fine-tuning of diuretics.”
The presentation drew such applause that one chairperson described it as “close to a standing ovation.” The study was published simultaneously in The Lancet.
Aggregate evidence
Early clinical evidence of the benefits of remote monitoring with the CardioMEMS-HF system was provided by the CHAMPION trial, which included patients with New York Heart Association (NYHA) class III heart failure.
Results of the subsequent GUIDE-HF trial, which aimed to test a broader population of patients with NYHA class II–IV heart failure and either increased N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations or hospitalization, were inconclusive.
However, a pre–COVID-19 impact analysis of GUIDE-HF indicated a possible benefit, which was primarily driven by a lower HF hospitalization rate, compared with the control group. That finding was the basis for an expanded indication for the system from the U.S. Food and Drug Administration.
The 2022 FDA indication permits the use of CardioMEMS for patients with NYHA class II HF and for those with worsening HF, as assessed by elevated natriuretic peptide levels.
From United States to Europe
Aware that most CardioMEMS data came from U.S. trials, the investigators embarked on the current trial, MONITOR-HF, an open-label, randomized trial in 25 centers in the Netherlands. Eligible patients had chronic NYHA class III HF, irrespective of ejection fraction, and had previously undergone hospitalization for HF.
A total of 348 patients were randomly assigned to either CardioMEMS-HF or standard of care (SoC) between 2019 and 2022.The median age of the patients was 69 years, and the median ejection fraction was 30%.
All patients were scheduled to be seen by their clinician at 3 months, 6 months, and every 6 months thereafter for up to 48 months.
The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score at 12 months
That difference between groups was 7.13 (+7.05 in the CardioMEMS group and –0.08 in the SoC group).
In the responder analysis, the odds ratio of an improvement of at least 5 points in the KCCQ overall summary score was 1.69 in the CardioMEMS group vs. the SoC group; the OR of a deterioration of at least 5 points was 0.45.
Subgroup analyses showed no relevant heterogeneity in the treatment effect on total HF hospitalizations and, notably, no significant interaction in patients with an EF below 40% and an EF above 40%.
There was a significant reduction in the median NT-proBNP change from baseline only in the remote monitoring group (800 pg/mL) and a smaller, nonsignificant difference with SoC.
Both groups received highly appropriate background guideline–directed medical therapy throughout the study. There were no significant between-group differences at 12 months.
Freedom from device-related or system-related complications and sensor failure were 97.7% and 98.8%, respectively.
Two sensor failures occurred during a mean follow-up 1.8 years. The percentage of failures was comparable to CHAMPION and GUIDE-HF trials.
The trial was not powered to assess a mortality benefit.
Pick the right patients
“As in the U.S. trials, there will be side effects, so select the right patients, because [remote monitoring] is not without risk,” Dr. Brugts told meeting attendees.
That point also was made by Christiane E. Angermann of University and University Hospital Würzburg, Germany, in a related editorial in The Lancet.
“To reproduce these results on a large scale in real-life health care, diligent patient selection should identify those at high risk of heart failure–related hospitalization who agree with the concept of daily data collection and are able and motivated to comply with treatment recommendations even if asymptomatic,” Dr. Angermann writes.
“Without direct interaction between health care providers and patients, and timely treatment modification triggered by abnormal monitoring results, the care cycle might break and the potential benefits from early detection of decompensation would be lost.”
Val Rakita, MD, assistant professor of medicine at Temple University, Philadelphia, a specialist in advanced heart failure and main implanter of the CardioMEMS device at Temple University Hospital, commented on the study for this article.
“This study confirms the previous data that the device is very safe and effective in preventing HF hospitalizations and improving patients’ quality of life, even in a different population with more modern background guideline-directed medical therapy.”
Nevertheless, he noted, “Studies have yet to confirm a mortality benefit, despite logic telling us that preventing heart failure hospitalizations should also improve patient survival. More studies are needed to see if a survival benefit can be proven over a longer follow-up period.”
Overall, he said, “Remote monitoring allows more precise management of medications, prevention of hospitalizations, and improvement in quality of life, and I am an advocate for it in my practice.”
Not everyone is an advocate, however. In a commentary published last year, John M. Mandrola, MD, a cardiac electrophysiologist at Baptist Medical Associates in Louisville, Ky., said the expanded FDA indication for the device is the result of “dubious trial analysis, spin, lax regulation, and the growth of low-value care.”
Others also have questioned the device’s value in the clinic.
But at least for now, as Dr. Angermann writes, “Scientific evidence supports the use of the CardioMEMS-HF system to enhance remote patient management in heart failure care. For more widespread application, technological advancements are desirable to provide more comfort for patients and reusable external device components, thereby improving care experience and saving resources.”
The MONITOR-HF trial is funded by the Dutch Ministry of Health and Health Care institute. Dr. Brugts has an independent research grant from Abbott (investigator-sponsored study) and has had speaker engagements or has participated in advisory boards for Abbott and other pharmaceutical companies. Dr. Angermann has received personal fees from Abbott for serving as chair of the steering committee for the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) and consulting fees, honoraria, and travel costs from Abbott. Dr. Rakita has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the first randomized clinical trial of remote pulmonary artery pressure–guided monitoring and management of chronic heart failure (HF) in Europe, the intervention “substantially” improved quality of life (QoL) and reduced HF hospitalizations, new data show.
The CardioMEMS-HF system (Abbot Laboratories) used in the trial, called MONITOR-HF, remotely monitors changes in pulmonary artery pressure and provides an early warning of worsening HF.
Jasper Brugts, MD, PhD, of Erasmus MC University Medical Centre, Rotterdam, the Netherlands, said in an interview, “The concordance on outcomes of the three CardioMEMS trials across different eras, evolving GDMT [guideline-directed medical therapy], different conditions (pandemic), and different health care systems is reassuring and supportive of technologies such as CardioMEMS to improve patient monitoring to prevent HF hospitalizations and improve QoL.”
Dr. Brugts presented the study at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions.
(11 vs. 17), in comparison with standard of care, Dr. Brugts told meeting attendees.
Furthermore, CardioMEMS monitors hypervolemia as well as hypovolemia, enabling “fine-tuning of diuretics.”
The presentation drew such applause that one chairperson described it as “close to a standing ovation.” The study was published simultaneously in The Lancet.
Aggregate evidence
Early clinical evidence of the benefits of remote monitoring with the CardioMEMS-HF system was provided by the CHAMPION trial, which included patients with New York Heart Association (NYHA) class III heart failure.
Results of the subsequent GUIDE-HF trial, which aimed to test a broader population of patients with NYHA class II–IV heart failure and either increased N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations or hospitalization, were inconclusive.
However, a pre–COVID-19 impact analysis of GUIDE-HF indicated a possible benefit, which was primarily driven by a lower HF hospitalization rate, compared with the control group. That finding was the basis for an expanded indication for the system from the U.S. Food and Drug Administration.
The 2022 FDA indication permits the use of CardioMEMS for patients with NYHA class II HF and for those with worsening HF, as assessed by elevated natriuretic peptide levels.
From United States to Europe
Aware that most CardioMEMS data came from U.S. trials, the investigators embarked on the current trial, MONITOR-HF, an open-label, randomized trial in 25 centers in the Netherlands. Eligible patients had chronic NYHA class III HF, irrespective of ejection fraction, and had previously undergone hospitalization for HF.
A total of 348 patients were randomly assigned to either CardioMEMS-HF or standard of care (SoC) between 2019 and 2022.The median age of the patients was 69 years, and the median ejection fraction was 30%.
All patients were scheduled to be seen by their clinician at 3 months, 6 months, and every 6 months thereafter for up to 48 months.
The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score at 12 months
That difference between groups was 7.13 (+7.05 in the CardioMEMS group and –0.08 in the SoC group).
In the responder analysis, the odds ratio of an improvement of at least 5 points in the KCCQ overall summary score was 1.69 in the CardioMEMS group vs. the SoC group; the OR of a deterioration of at least 5 points was 0.45.
Subgroup analyses showed no relevant heterogeneity in the treatment effect on total HF hospitalizations and, notably, no significant interaction in patients with an EF below 40% and an EF above 40%.
There was a significant reduction in the median NT-proBNP change from baseline only in the remote monitoring group (800 pg/mL) and a smaller, nonsignificant difference with SoC.
Both groups received highly appropriate background guideline–directed medical therapy throughout the study. There were no significant between-group differences at 12 months.
Freedom from device-related or system-related complications and sensor failure were 97.7% and 98.8%, respectively.
Two sensor failures occurred during a mean follow-up 1.8 years. The percentage of failures was comparable to CHAMPION and GUIDE-HF trials.
The trial was not powered to assess a mortality benefit.
Pick the right patients
“As in the U.S. trials, there will be side effects, so select the right patients, because [remote monitoring] is not without risk,” Dr. Brugts told meeting attendees.
That point also was made by Christiane E. Angermann of University and University Hospital Würzburg, Germany, in a related editorial in The Lancet.
“To reproduce these results on a large scale in real-life health care, diligent patient selection should identify those at high risk of heart failure–related hospitalization who agree with the concept of daily data collection and are able and motivated to comply with treatment recommendations even if asymptomatic,” Dr. Angermann writes.
“Without direct interaction between health care providers and patients, and timely treatment modification triggered by abnormal monitoring results, the care cycle might break and the potential benefits from early detection of decompensation would be lost.”
Val Rakita, MD, assistant professor of medicine at Temple University, Philadelphia, a specialist in advanced heart failure and main implanter of the CardioMEMS device at Temple University Hospital, commented on the study for this article.
“This study confirms the previous data that the device is very safe and effective in preventing HF hospitalizations and improving patients’ quality of life, even in a different population with more modern background guideline-directed medical therapy.”
Nevertheless, he noted, “Studies have yet to confirm a mortality benefit, despite logic telling us that preventing heart failure hospitalizations should also improve patient survival. More studies are needed to see if a survival benefit can be proven over a longer follow-up period.”
Overall, he said, “Remote monitoring allows more precise management of medications, prevention of hospitalizations, and improvement in quality of life, and I am an advocate for it in my practice.”
Not everyone is an advocate, however. In a commentary published last year, John M. Mandrola, MD, a cardiac electrophysiologist at Baptist Medical Associates in Louisville, Ky., said the expanded FDA indication for the device is the result of “dubious trial analysis, spin, lax regulation, and the growth of low-value care.”
Others also have questioned the device’s value in the clinic.
But at least for now, as Dr. Angermann writes, “Scientific evidence supports the use of the CardioMEMS-HF system to enhance remote patient management in heart failure care. For more widespread application, technological advancements are desirable to provide more comfort for patients and reusable external device components, thereby improving care experience and saving resources.”
The MONITOR-HF trial is funded by the Dutch Ministry of Health and Health Care institute. Dr. Brugts has an independent research grant from Abbott (investigator-sponsored study) and has had speaker engagements or has participated in advisory boards for Abbott and other pharmaceutical companies. Dr. Angermann has received personal fees from Abbott for serving as chair of the steering committee for the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) and consulting fees, honoraria, and travel costs from Abbott. Dr. Rakita has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ESC HEART FAILURE 2023
Novel antibody safe, promising for ATTR in phase 1 trial
, a new study suggests.
Currently, the only drug approved to treat ATTR is tafamidis, which improves survival and reduces hospitalizations, but does not reverse disease symptoms, the authors noted.
NI006 is a recombinant human anti-ATTR antibody given by infusion that was developed to trigger removal of ATTR by the body’s phagocytic immune cells.
Use of the drug was not associated with serious drug-related adverse events, though mild and moderate adverse events did occur.
Median N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin T levels also seemed to be reduced over the study period.
Given the success of the antibody in this initial 40-patient trial, a larger phase-3 placebo-controlled trial is planned and expected to launch in the second half of 2023, said lead author Pablo Garcia-Pavia, MD, of Hospital Universitario Puerta de Hierro and the Spanish National Cardiovascular Research Institute, Madrid.
However, “The design of appropriate phase-3 trials to demonstrate efficacy of drugs for ATTR-CM is becoming more complicated and challenging,” he said.
“Increased awareness of the disease and advances in cardiac imaging techniques have led to recognition of a larger number of patients with ATTR-CM who have a different clinical profile and a different prognosis than the patients who were diagnosed in previous years and were enrolled in the initial trials of stabilizers,” Dr. Garcia-Pavia added.
“Moreover, the availability of tafamidis, and hopefully soon other medications to treat ATTR-CM has complicated the design of new clinical trials because of the heterogenicity of treatments that patients might receive,” he said. “Therefore, it is critical to plan the design very well.”
Dr. Garcia-Pavia presented the findings on NI006 at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions. The study was published simultaneously in the New England Journal of Medicine.
No serious adverse events
For the phase-1, double-blind, multicenter study, the investigators randomly assigned (2:1 ratio) 40 patients (median age, 72 years; 98% men) with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive IV infusions of either NI006, at one of six doses ranging from 0.3 mg/kg to 60 mg/kg of body weight, or placebo every 4 weeks for 4 months.
After the four infusions, participants were enrolled in an open-label extension phase in which they received eight NI006 infusions with stepwise increases in the dose.
Participants had a confirmed diagnosis of ATTR-CM; left ventricular wall thickness of at least 14 mm; left ventricular ejection fraction of at least 40%; New York Heart Association class I, II, or III; estimated glomerular filtration rate of more than 30 mL/min per 1.73 m2; and an NT-proBNP level of 600 to 6,000 pg/mL.
Most (36) were receiving tafamidis, with a median treatment duration of 7 months; other ATTR-specific drugs were not permitted. Patients randomly assigned to receive NI006 seemed to have more advanced disease compared with those assigned to placebo.
Adherence to the trial protocol was high: Thirty-four patients received the four scheduled infusions during the ascending-dose phase, and 34 of 35 patients who completed this phase subsequently enrolled in the open-label extension.
No apparent drug-related serious adverse events were reported. However, during the ascending-dose phase, 38 patients had at least one adverse event, most of which were mild or moderate; of the 191 total events, 124 were grade 1 and 60 were grade 2 (most commonly heart failure and arrhythmias). Three patients had cytokine release syndrome; all three completed treatment through the extension phase.
Musculoskeletal events increased with ascending doses of NI006, which led two patients to withdraw from the trial.
At doses of at least 10 mg/kg, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over 12 months.
Because NI006 stimulates the patient’s own immune system to eliminate cardiac amyloid fibrils, one session chair at the meeting wondered whether NI006 represented the “rise of immunology in cardiology,” and whether biologics might follow.
Another questioned how removing amyloid might affect cardiac function. The echocardiographic findings gathered so far don’t indicate dysfunction, “but this is a small trial, and we need more data,” Dr. Garcia-Pavia said.
Tempered excitement
In a comment, Ronald Witteles, MD, professor of cardiovascular medicine, Stanford (Calif.) University, and founder/codirector of the Stanford Amyloid Center, said that “antibody-based amyloid removal strategies are not currently clinically available and represent a fundamentally different mechanism to treat the disease from what we currently have.
“While the data are encouraging and will generate excitement for later-phase studies, we’re talking about small numbers of patients and nothing definitive should be drawn from this data,” said Dr. Witteles, deputy editor of JACC: CardioOncology.
“The biggest caveat is that similar approaches of antibody removal of amyloid deposits for other forms of amyloidosis — most notably AL amyloidosis (amyloid light chain or primary amyloidosis) – have failed in late-phase trials. Although there is reason to believe that ATTR amyloidosis may be more amenable to improvements with amyloid fibril removal than AL amyloidosis, the unimpressive results in other forms of amyloidosis still do temper the excitement to a degree.”
Like Dr. Garcia-Pavia, Dr. Witteles said, “Ultimately, we are going to need to see a phase 3 clinical trial which shows that NI006 – on top of standard-of-care treatment – improves hard outcomes in the disease. As treatment options likely expand in the coming years, that is likely to be a harder and harder bar to reach.”
Furthermore, although the safety profile was favorable overall, it “wasn’t entirely clean,” given cytokine release syndrome in three patients, a lowering of platelet counts in a couple of patients, and musculoskeletal side effects that triggered two to withdraw from the study. “Unless that changes,” he said, “that will be a barrier for some patients.”
Overall, he noted, “With the vast majority of patients being able to be diagnosed noninvasively, and with treatment options now available, we have seen a true explosion in the number of patients being diagnosed.
“But we also know that the large majority ... are still not getting diagnosed or are having huge delays in diagnosis. As such, the biggest thing we can do for patients with the disease is to continue to educate people about it,” Dr. Witteles concluded.
The study was funded by Neurimmune. Dr. Garcia-Pavia disclosed ties to Alexion, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio, General Electric, Intellia, Ionis Pharmaceuticals, Neurimmune, Novo Nordisk, and Pfizer. Dr. Witteles reported ties to Alexion, Alnylam, AstraZeneca, BridgeBio, Intellia, Ionis, Janssen, Novo Nordisk, and Pfizer.
A version of this article first appeared on Medscape.com.
, a new study suggests.
Currently, the only drug approved to treat ATTR is tafamidis, which improves survival and reduces hospitalizations, but does not reverse disease symptoms, the authors noted.
NI006 is a recombinant human anti-ATTR antibody given by infusion that was developed to trigger removal of ATTR by the body’s phagocytic immune cells.
Use of the drug was not associated with serious drug-related adverse events, though mild and moderate adverse events did occur.
Median N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin T levels also seemed to be reduced over the study period.
Given the success of the antibody in this initial 40-patient trial, a larger phase-3 placebo-controlled trial is planned and expected to launch in the second half of 2023, said lead author Pablo Garcia-Pavia, MD, of Hospital Universitario Puerta de Hierro and the Spanish National Cardiovascular Research Institute, Madrid.
However, “The design of appropriate phase-3 trials to demonstrate efficacy of drugs for ATTR-CM is becoming more complicated and challenging,” he said.
“Increased awareness of the disease and advances in cardiac imaging techniques have led to recognition of a larger number of patients with ATTR-CM who have a different clinical profile and a different prognosis than the patients who were diagnosed in previous years and were enrolled in the initial trials of stabilizers,” Dr. Garcia-Pavia added.
“Moreover, the availability of tafamidis, and hopefully soon other medications to treat ATTR-CM has complicated the design of new clinical trials because of the heterogenicity of treatments that patients might receive,” he said. “Therefore, it is critical to plan the design very well.”
Dr. Garcia-Pavia presented the findings on NI006 at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions. The study was published simultaneously in the New England Journal of Medicine.
No serious adverse events
For the phase-1, double-blind, multicenter study, the investigators randomly assigned (2:1 ratio) 40 patients (median age, 72 years; 98% men) with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive IV infusions of either NI006, at one of six doses ranging from 0.3 mg/kg to 60 mg/kg of body weight, or placebo every 4 weeks for 4 months.
After the four infusions, participants were enrolled in an open-label extension phase in which they received eight NI006 infusions with stepwise increases in the dose.
Participants had a confirmed diagnosis of ATTR-CM; left ventricular wall thickness of at least 14 mm; left ventricular ejection fraction of at least 40%; New York Heart Association class I, II, or III; estimated glomerular filtration rate of more than 30 mL/min per 1.73 m2; and an NT-proBNP level of 600 to 6,000 pg/mL.
Most (36) were receiving tafamidis, with a median treatment duration of 7 months; other ATTR-specific drugs were not permitted. Patients randomly assigned to receive NI006 seemed to have more advanced disease compared with those assigned to placebo.
Adherence to the trial protocol was high: Thirty-four patients received the four scheduled infusions during the ascending-dose phase, and 34 of 35 patients who completed this phase subsequently enrolled in the open-label extension.
No apparent drug-related serious adverse events were reported. However, during the ascending-dose phase, 38 patients had at least one adverse event, most of which were mild or moderate; of the 191 total events, 124 were grade 1 and 60 were grade 2 (most commonly heart failure and arrhythmias). Three patients had cytokine release syndrome; all three completed treatment through the extension phase.
Musculoskeletal events increased with ascending doses of NI006, which led two patients to withdraw from the trial.
At doses of at least 10 mg/kg, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over 12 months.
Because NI006 stimulates the patient’s own immune system to eliminate cardiac amyloid fibrils, one session chair at the meeting wondered whether NI006 represented the “rise of immunology in cardiology,” and whether biologics might follow.
Another questioned how removing amyloid might affect cardiac function. The echocardiographic findings gathered so far don’t indicate dysfunction, “but this is a small trial, and we need more data,” Dr. Garcia-Pavia said.
Tempered excitement
In a comment, Ronald Witteles, MD, professor of cardiovascular medicine, Stanford (Calif.) University, and founder/codirector of the Stanford Amyloid Center, said that “antibody-based amyloid removal strategies are not currently clinically available and represent a fundamentally different mechanism to treat the disease from what we currently have.
“While the data are encouraging and will generate excitement for later-phase studies, we’re talking about small numbers of patients and nothing definitive should be drawn from this data,” said Dr. Witteles, deputy editor of JACC: CardioOncology.
“The biggest caveat is that similar approaches of antibody removal of amyloid deposits for other forms of amyloidosis — most notably AL amyloidosis (amyloid light chain or primary amyloidosis) – have failed in late-phase trials. Although there is reason to believe that ATTR amyloidosis may be more amenable to improvements with amyloid fibril removal than AL amyloidosis, the unimpressive results in other forms of amyloidosis still do temper the excitement to a degree.”
Like Dr. Garcia-Pavia, Dr. Witteles said, “Ultimately, we are going to need to see a phase 3 clinical trial which shows that NI006 – on top of standard-of-care treatment – improves hard outcomes in the disease. As treatment options likely expand in the coming years, that is likely to be a harder and harder bar to reach.”
Furthermore, although the safety profile was favorable overall, it “wasn’t entirely clean,” given cytokine release syndrome in three patients, a lowering of platelet counts in a couple of patients, and musculoskeletal side effects that triggered two to withdraw from the study. “Unless that changes,” he said, “that will be a barrier for some patients.”
Overall, he noted, “With the vast majority of patients being able to be diagnosed noninvasively, and with treatment options now available, we have seen a true explosion in the number of patients being diagnosed.
“But we also know that the large majority ... are still not getting diagnosed or are having huge delays in diagnosis. As such, the biggest thing we can do for patients with the disease is to continue to educate people about it,” Dr. Witteles concluded.
The study was funded by Neurimmune. Dr. Garcia-Pavia disclosed ties to Alexion, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio, General Electric, Intellia, Ionis Pharmaceuticals, Neurimmune, Novo Nordisk, and Pfizer. Dr. Witteles reported ties to Alexion, Alnylam, AstraZeneca, BridgeBio, Intellia, Ionis, Janssen, Novo Nordisk, and Pfizer.
A version of this article first appeared on Medscape.com.
, a new study suggests.
Currently, the only drug approved to treat ATTR is tafamidis, which improves survival and reduces hospitalizations, but does not reverse disease symptoms, the authors noted.
NI006 is a recombinant human anti-ATTR antibody given by infusion that was developed to trigger removal of ATTR by the body’s phagocytic immune cells.
Use of the drug was not associated with serious drug-related adverse events, though mild and moderate adverse events did occur.
Median N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin T levels also seemed to be reduced over the study period.
Given the success of the antibody in this initial 40-patient trial, a larger phase-3 placebo-controlled trial is planned and expected to launch in the second half of 2023, said lead author Pablo Garcia-Pavia, MD, of Hospital Universitario Puerta de Hierro and the Spanish National Cardiovascular Research Institute, Madrid.
However, “The design of appropriate phase-3 trials to demonstrate efficacy of drugs for ATTR-CM is becoming more complicated and challenging,” he said.
“Increased awareness of the disease and advances in cardiac imaging techniques have led to recognition of a larger number of patients with ATTR-CM who have a different clinical profile and a different prognosis than the patients who were diagnosed in previous years and were enrolled in the initial trials of stabilizers,” Dr. Garcia-Pavia added.
“Moreover, the availability of tafamidis, and hopefully soon other medications to treat ATTR-CM has complicated the design of new clinical trials because of the heterogenicity of treatments that patients might receive,” he said. “Therefore, it is critical to plan the design very well.”
Dr. Garcia-Pavia presented the findings on NI006 at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions. The study was published simultaneously in the New England Journal of Medicine.
No serious adverse events
For the phase-1, double-blind, multicenter study, the investigators randomly assigned (2:1 ratio) 40 patients (median age, 72 years; 98% men) with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive IV infusions of either NI006, at one of six doses ranging from 0.3 mg/kg to 60 mg/kg of body weight, or placebo every 4 weeks for 4 months.
After the four infusions, participants were enrolled in an open-label extension phase in which they received eight NI006 infusions with stepwise increases in the dose.
Participants had a confirmed diagnosis of ATTR-CM; left ventricular wall thickness of at least 14 mm; left ventricular ejection fraction of at least 40%; New York Heart Association class I, II, or III; estimated glomerular filtration rate of more than 30 mL/min per 1.73 m2; and an NT-proBNP level of 600 to 6,000 pg/mL.
Most (36) were receiving tafamidis, with a median treatment duration of 7 months; other ATTR-specific drugs were not permitted. Patients randomly assigned to receive NI006 seemed to have more advanced disease compared with those assigned to placebo.
Adherence to the trial protocol was high: Thirty-four patients received the four scheduled infusions during the ascending-dose phase, and 34 of 35 patients who completed this phase subsequently enrolled in the open-label extension.
No apparent drug-related serious adverse events were reported. However, during the ascending-dose phase, 38 patients had at least one adverse event, most of which were mild or moderate; of the 191 total events, 124 were grade 1 and 60 were grade 2 (most commonly heart failure and arrhythmias). Three patients had cytokine release syndrome; all three completed treatment through the extension phase.
Musculoskeletal events increased with ascending doses of NI006, which led two patients to withdraw from the trial.
At doses of at least 10 mg/kg, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over 12 months.
Because NI006 stimulates the patient’s own immune system to eliminate cardiac amyloid fibrils, one session chair at the meeting wondered whether NI006 represented the “rise of immunology in cardiology,” and whether biologics might follow.
Another questioned how removing amyloid might affect cardiac function. The echocardiographic findings gathered so far don’t indicate dysfunction, “but this is a small trial, and we need more data,” Dr. Garcia-Pavia said.
Tempered excitement
In a comment, Ronald Witteles, MD, professor of cardiovascular medicine, Stanford (Calif.) University, and founder/codirector of the Stanford Amyloid Center, said that “antibody-based amyloid removal strategies are not currently clinically available and represent a fundamentally different mechanism to treat the disease from what we currently have.
“While the data are encouraging and will generate excitement for later-phase studies, we’re talking about small numbers of patients and nothing definitive should be drawn from this data,” said Dr. Witteles, deputy editor of JACC: CardioOncology.
“The biggest caveat is that similar approaches of antibody removal of amyloid deposits for other forms of amyloidosis — most notably AL amyloidosis (amyloid light chain or primary amyloidosis) – have failed in late-phase trials. Although there is reason to believe that ATTR amyloidosis may be more amenable to improvements with amyloid fibril removal than AL amyloidosis, the unimpressive results in other forms of amyloidosis still do temper the excitement to a degree.”
Like Dr. Garcia-Pavia, Dr. Witteles said, “Ultimately, we are going to need to see a phase 3 clinical trial which shows that NI006 – on top of standard-of-care treatment – improves hard outcomes in the disease. As treatment options likely expand in the coming years, that is likely to be a harder and harder bar to reach.”
Furthermore, although the safety profile was favorable overall, it “wasn’t entirely clean,” given cytokine release syndrome in three patients, a lowering of platelet counts in a couple of patients, and musculoskeletal side effects that triggered two to withdraw from the study. “Unless that changes,” he said, “that will be a barrier for some patients.”
Overall, he noted, “With the vast majority of patients being able to be diagnosed noninvasively, and with treatment options now available, we have seen a true explosion in the number of patients being diagnosed.
“But we also know that the large majority ... are still not getting diagnosed or are having huge delays in diagnosis. As such, the biggest thing we can do for patients with the disease is to continue to educate people about it,” Dr. Witteles concluded.
The study was funded by Neurimmune. Dr. Garcia-Pavia disclosed ties to Alexion, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio, General Electric, Intellia, Ionis Pharmaceuticals, Neurimmune, Novo Nordisk, and Pfizer. Dr. Witteles reported ties to Alexion, Alnylam, AstraZeneca, BridgeBio, Intellia, Ionis, Janssen, Novo Nordisk, and Pfizer.
A version of this article first appeared on Medscape.com.
FROM ESC HEART FAILURE 2023
Video-based AI tool estimates LVEF from angiograms
a new study suggests.
In the test dataset, the video-based algorithm, called a deep neural network (DNN), discriminated reduced LVEF (< 40%) with an area under the receiver operating characteristic curve of 0.911.
In the external validation dataset, the DNN discriminated reduced LVEF with an AUROC of 0.906. However, the DNN tended to overestimate low LVEFs and to underestimate high LVEFs.
“We know the findings will be unexpected for cardiologists who don’t typically expect to get an estimate of systolic function or pump function just from an angiogram,” principal investigator Geoffrey H. Tison, MD, of the University of California, San Francisco, said in an interview.
In fact, he noted, “one of the challenges we face is a lack of trust by the health care community. They may not understand what drives the predictions behind our models. We have to translate that information in such a way that physicians trust that the algorithm is using the right features from the data they feed in to make the predictions.”
To help bolster that trust, “we display the ‘Model Facts,’ a nutrition-style label that describes how we train the algorithm, how it was validated, and the inclusion and exclusion criteria,” added lead author Robert Avram, MD, of the University of Montreal.
Model Facts is a safeguard against inappropriate use of the algorithm, Dr. Avram said. For example, if the algorithm was trained on patients between the ages of 40 and 90 and a clinician fed in data for a 35-year-old, a pop-up would appear warning the physician that the data being inputted are different from the data the algorithm was trained and validated on, and so any prediction “should be taken with a grain of salt.”
The study was published online in JAMA Cardiology.
Additional procedure
LVEF can be determined before coronary angiography with transthoracic echocardiography, but that is not always available, particularly for patients being seen emergently for acute coronary syndromes, the researchers wrote. LVEF can also be assessed using left ventriculography, an additional procedure that requires insertion of a pigtail catheter into the left ventricle and injection of more contrast and longer radiation exposure.
“Novel methods to assess LVEF at the point of care during coronary angiography would expand the available options to perform this important physiologic determination,” they wrote. “Video-based deep neural networks can learn subtle patterns from medical data to accomplish certain tasks beyond what physicians can achieve with that data, providing an opportunity to assess cardiac systolic function in real time from standard angiographic images without additional cost or procedures.”
The investigators conducted a cross-sectional study using UCSF patient data from 2012 to 2019. Data were randomly categorized into training, development, and test datasets.
External validation data were obtained from the University of Ottawa Heart Institute.
All adult patients who received a coronary angiogram and a transthoracic echocardiogram (TTE) within 3 months before or 1 month after receiving the angiogram were included.
A total of 4,042 angiograms with corresponding TTE LVEF from 3,679 UCSF patients were included in the analysis. The mean age of the patients was 64.3 years, and 65% were men.
The researchers’ video-based DNN, called CathEF, was used to discriminate reduced LVEF and to predict a continuous LVEF percentage from standard angiogram videos of the left coronary artery.
In the UCSF test dataset, CathEF discriminated reduced LVEF with an AUROC of 0.911; the diagnostic odds ratio for reduced LVEF was 22.7.
Furthermore, the CathEF-predicted that LVEF had a mean absolute error (MAE) of 8.5%, compared with TTE LVEF.
The CathEF-predicted LVEF differed 5% or less in comparison with the TTE LVEF in 38% of the test dataset studies; however, differences greater than 15% were seen in 15.2% of cases.
In the external validation, CathEF discriminated reduced LVEF with an AUROC of 0.906 and an MAE of 7%.
CathEF performance was consistent irrespective of patient characteristics, including sex, body mass index, low estimated glomerular filtration rate (< 45), acute coronary syndromes, obstructive coronary artery disease, and left ventricular hypertrophy.
However, as noted, it tended to overestimate low LVEFs and to underestimate high LVEFs.
“Further research can improve accuracy and reduce the variability of DNNs to maximize their clinical utility,” the authors concluded.
A validation study is underway at the Montreal Heart Institute, and similar studies are planned at UCSF and McGill University, Dr. Tison said. “We expect to present preliminary findings at medical conferences either before the end of the year or maybe for the American College of Cardiology meeting in March 2024.”
Potentially improved outcomes
In a comment, Alfonso H. Waller, MD, a member of the American College of Cardiology’s Imaging Council and director of cardiac imaging at New Jersey Medical School, Newark, said that, “at some centers, in patients presenting with an acute ST-segment elevation myocardial infarction, some argue that assessment of myocardial and valvular function with [left ventriculography] grams may provide important prognostic information and in part may help guide the management of the patient.
“Therefore, this novel approach may provide information that is not usually available without performing a classic LV gram ... [and] may lead to improved delivery of care, earlier therapies, and potentially improved outcomes and quality of life.”
If the technology is available in real time, “it could enable real-time, dynamic assessment of cardiac function during coronary angiography, which may be particularly helpful in acute STEMI cases where baseline cardiac function and renal function may be unknown and additional contrast may be detrimental,” he said.
However, patients who might benefit most from the technology are those with severely reduced LVEF, “and unfortunately, the LVEF may be overestimated in this group,” he said.
Dr. Waller also noted that the model was developed using echocardiograms obtained 3 months before or up to 1 month after the angiogram, during which time “LVEF may change significantly. Typically, if someone presents with an acute coronary syndrome, there can be myocardial stunning, which can lead to regional wall motion abnormalities and lowering of LVEF.”
The validation study is evaluating patients with acute coronary syndrome for whom an echocardiogram was performed within 48 hours of the angiogram, he added.
The study was supported by grants from the Fonds de la Recherche en Santé du Québec, the Montreal Heart Institute Research Centre, the Montreal Heart Institute Foundation, the Des Groseillers-Bérard Research Chair, the National Institutes of Health, and the Heart and Stroke Foundation of Ontario. Dr. Tison, Dr. Avram, and Dr. Waller disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new study suggests.
In the test dataset, the video-based algorithm, called a deep neural network (DNN), discriminated reduced LVEF (< 40%) with an area under the receiver operating characteristic curve of 0.911.
In the external validation dataset, the DNN discriminated reduced LVEF with an AUROC of 0.906. However, the DNN tended to overestimate low LVEFs and to underestimate high LVEFs.
“We know the findings will be unexpected for cardiologists who don’t typically expect to get an estimate of systolic function or pump function just from an angiogram,” principal investigator Geoffrey H. Tison, MD, of the University of California, San Francisco, said in an interview.
In fact, he noted, “one of the challenges we face is a lack of trust by the health care community. They may not understand what drives the predictions behind our models. We have to translate that information in such a way that physicians trust that the algorithm is using the right features from the data they feed in to make the predictions.”
To help bolster that trust, “we display the ‘Model Facts,’ a nutrition-style label that describes how we train the algorithm, how it was validated, and the inclusion and exclusion criteria,” added lead author Robert Avram, MD, of the University of Montreal.
Model Facts is a safeguard against inappropriate use of the algorithm, Dr. Avram said. For example, if the algorithm was trained on patients between the ages of 40 and 90 and a clinician fed in data for a 35-year-old, a pop-up would appear warning the physician that the data being inputted are different from the data the algorithm was trained and validated on, and so any prediction “should be taken with a grain of salt.”
The study was published online in JAMA Cardiology.
Additional procedure
LVEF can be determined before coronary angiography with transthoracic echocardiography, but that is not always available, particularly for patients being seen emergently for acute coronary syndromes, the researchers wrote. LVEF can also be assessed using left ventriculography, an additional procedure that requires insertion of a pigtail catheter into the left ventricle and injection of more contrast and longer radiation exposure.
“Novel methods to assess LVEF at the point of care during coronary angiography would expand the available options to perform this important physiologic determination,” they wrote. “Video-based deep neural networks can learn subtle patterns from medical data to accomplish certain tasks beyond what physicians can achieve with that data, providing an opportunity to assess cardiac systolic function in real time from standard angiographic images without additional cost or procedures.”
The investigators conducted a cross-sectional study using UCSF patient data from 2012 to 2019. Data were randomly categorized into training, development, and test datasets.
External validation data were obtained from the University of Ottawa Heart Institute.
All adult patients who received a coronary angiogram and a transthoracic echocardiogram (TTE) within 3 months before or 1 month after receiving the angiogram were included.
A total of 4,042 angiograms with corresponding TTE LVEF from 3,679 UCSF patients were included in the analysis. The mean age of the patients was 64.3 years, and 65% were men.
The researchers’ video-based DNN, called CathEF, was used to discriminate reduced LVEF and to predict a continuous LVEF percentage from standard angiogram videos of the left coronary artery.
In the UCSF test dataset, CathEF discriminated reduced LVEF with an AUROC of 0.911; the diagnostic odds ratio for reduced LVEF was 22.7.
Furthermore, the CathEF-predicted that LVEF had a mean absolute error (MAE) of 8.5%, compared with TTE LVEF.
The CathEF-predicted LVEF differed 5% or less in comparison with the TTE LVEF in 38% of the test dataset studies; however, differences greater than 15% were seen in 15.2% of cases.
In the external validation, CathEF discriminated reduced LVEF with an AUROC of 0.906 and an MAE of 7%.
CathEF performance was consistent irrespective of patient characteristics, including sex, body mass index, low estimated glomerular filtration rate (< 45), acute coronary syndromes, obstructive coronary artery disease, and left ventricular hypertrophy.
However, as noted, it tended to overestimate low LVEFs and to underestimate high LVEFs.
“Further research can improve accuracy and reduce the variability of DNNs to maximize their clinical utility,” the authors concluded.
A validation study is underway at the Montreal Heart Institute, and similar studies are planned at UCSF and McGill University, Dr. Tison said. “We expect to present preliminary findings at medical conferences either before the end of the year or maybe for the American College of Cardiology meeting in March 2024.”
Potentially improved outcomes
In a comment, Alfonso H. Waller, MD, a member of the American College of Cardiology’s Imaging Council and director of cardiac imaging at New Jersey Medical School, Newark, said that, “at some centers, in patients presenting with an acute ST-segment elevation myocardial infarction, some argue that assessment of myocardial and valvular function with [left ventriculography] grams may provide important prognostic information and in part may help guide the management of the patient.
“Therefore, this novel approach may provide information that is not usually available without performing a classic LV gram ... [and] may lead to improved delivery of care, earlier therapies, and potentially improved outcomes and quality of life.”
If the technology is available in real time, “it could enable real-time, dynamic assessment of cardiac function during coronary angiography, which may be particularly helpful in acute STEMI cases where baseline cardiac function and renal function may be unknown and additional contrast may be detrimental,” he said.
However, patients who might benefit most from the technology are those with severely reduced LVEF, “and unfortunately, the LVEF may be overestimated in this group,” he said.
Dr. Waller also noted that the model was developed using echocardiograms obtained 3 months before or up to 1 month after the angiogram, during which time “LVEF may change significantly. Typically, if someone presents with an acute coronary syndrome, there can be myocardial stunning, which can lead to regional wall motion abnormalities and lowering of LVEF.”
The validation study is evaluating patients with acute coronary syndrome for whom an echocardiogram was performed within 48 hours of the angiogram, he added.
The study was supported by grants from the Fonds de la Recherche en Santé du Québec, the Montreal Heart Institute Research Centre, the Montreal Heart Institute Foundation, the Des Groseillers-Bérard Research Chair, the National Institutes of Health, and the Heart and Stroke Foundation of Ontario. Dr. Tison, Dr. Avram, and Dr. Waller disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new study suggests.
In the test dataset, the video-based algorithm, called a deep neural network (DNN), discriminated reduced LVEF (< 40%) with an area under the receiver operating characteristic curve of 0.911.
In the external validation dataset, the DNN discriminated reduced LVEF with an AUROC of 0.906. However, the DNN tended to overestimate low LVEFs and to underestimate high LVEFs.
“We know the findings will be unexpected for cardiologists who don’t typically expect to get an estimate of systolic function or pump function just from an angiogram,” principal investigator Geoffrey H. Tison, MD, of the University of California, San Francisco, said in an interview.
In fact, he noted, “one of the challenges we face is a lack of trust by the health care community. They may not understand what drives the predictions behind our models. We have to translate that information in such a way that physicians trust that the algorithm is using the right features from the data they feed in to make the predictions.”
To help bolster that trust, “we display the ‘Model Facts,’ a nutrition-style label that describes how we train the algorithm, how it was validated, and the inclusion and exclusion criteria,” added lead author Robert Avram, MD, of the University of Montreal.
Model Facts is a safeguard against inappropriate use of the algorithm, Dr. Avram said. For example, if the algorithm was trained on patients between the ages of 40 and 90 and a clinician fed in data for a 35-year-old, a pop-up would appear warning the physician that the data being inputted are different from the data the algorithm was trained and validated on, and so any prediction “should be taken with a grain of salt.”
The study was published online in JAMA Cardiology.
Additional procedure
LVEF can be determined before coronary angiography with transthoracic echocardiography, but that is not always available, particularly for patients being seen emergently for acute coronary syndromes, the researchers wrote. LVEF can also be assessed using left ventriculography, an additional procedure that requires insertion of a pigtail catheter into the left ventricle and injection of more contrast and longer radiation exposure.
“Novel methods to assess LVEF at the point of care during coronary angiography would expand the available options to perform this important physiologic determination,” they wrote. “Video-based deep neural networks can learn subtle patterns from medical data to accomplish certain tasks beyond what physicians can achieve with that data, providing an opportunity to assess cardiac systolic function in real time from standard angiographic images without additional cost or procedures.”
The investigators conducted a cross-sectional study using UCSF patient data from 2012 to 2019. Data were randomly categorized into training, development, and test datasets.
External validation data were obtained from the University of Ottawa Heart Institute.
All adult patients who received a coronary angiogram and a transthoracic echocardiogram (TTE) within 3 months before or 1 month after receiving the angiogram were included.
A total of 4,042 angiograms with corresponding TTE LVEF from 3,679 UCSF patients were included in the analysis. The mean age of the patients was 64.3 years, and 65% were men.
The researchers’ video-based DNN, called CathEF, was used to discriminate reduced LVEF and to predict a continuous LVEF percentage from standard angiogram videos of the left coronary artery.
In the UCSF test dataset, CathEF discriminated reduced LVEF with an AUROC of 0.911; the diagnostic odds ratio for reduced LVEF was 22.7.
Furthermore, the CathEF-predicted that LVEF had a mean absolute error (MAE) of 8.5%, compared with TTE LVEF.
The CathEF-predicted LVEF differed 5% or less in comparison with the TTE LVEF in 38% of the test dataset studies; however, differences greater than 15% were seen in 15.2% of cases.
In the external validation, CathEF discriminated reduced LVEF with an AUROC of 0.906 and an MAE of 7%.
CathEF performance was consistent irrespective of patient characteristics, including sex, body mass index, low estimated glomerular filtration rate (< 45), acute coronary syndromes, obstructive coronary artery disease, and left ventricular hypertrophy.
However, as noted, it tended to overestimate low LVEFs and to underestimate high LVEFs.
“Further research can improve accuracy and reduce the variability of DNNs to maximize their clinical utility,” the authors concluded.
A validation study is underway at the Montreal Heart Institute, and similar studies are planned at UCSF and McGill University, Dr. Tison said. “We expect to present preliminary findings at medical conferences either before the end of the year or maybe for the American College of Cardiology meeting in March 2024.”
Potentially improved outcomes
In a comment, Alfonso H. Waller, MD, a member of the American College of Cardiology’s Imaging Council and director of cardiac imaging at New Jersey Medical School, Newark, said that, “at some centers, in patients presenting with an acute ST-segment elevation myocardial infarction, some argue that assessment of myocardial and valvular function with [left ventriculography] grams may provide important prognostic information and in part may help guide the management of the patient.
“Therefore, this novel approach may provide information that is not usually available without performing a classic LV gram ... [and] may lead to improved delivery of care, earlier therapies, and potentially improved outcomes and quality of life.”
If the technology is available in real time, “it could enable real-time, dynamic assessment of cardiac function during coronary angiography, which may be particularly helpful in acute STEMI cases where baseline cardiac function and renal function may be unknown and additional contrast may be detrimental,” he said.
However, patients who might benefit most from the technology are those with severely reduced LVEF, “and unfortunately, the LVEF may be overestimated in this group,” he said.
Dr. Waller also noted that the model was developed using echocardiograms obtained 3 months before or up to 1 month after the angiogram, during which time “LVEF may change significantly. Typically, if someone presents with an acute coronary syndrome, there can be myocardial stunning, which can lead to regional wall motion abnormalities and lowering of LVEF.”
The validation study is evaluating patients with acute coronary syndrome for whom an echocardiogram was performed within 48 hours of the angiogram, he added.
The study was supported by grants from the Fonds de la Recherche en Santé du Québec, the Montreal Heart Institute Research Centre, the Montreal Heart Institute Foundation, the Des Groseillers-Bérard Research Chair, the National Institutes of Health, and the Heart and Stroke Foundation of Ontario. Dr. Tison, Dr. Avram, and Dr. Waller disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY
Hyperbaric oxygen may improve heart function in long COVID
.
Patients with reduced left ventricular global longitudinal strain (GLS) at baseline who received HBOT had a significant increase in GLS, compared with those who received sham treatment.
GLS is a measure of systolic function that is thought to be a predictor of heart failure–related outcomes.
The study also showed that global work efficiency (GWE) and the global work index (GWI) increased in HBOT-treated patients, though not significantly.
“HBOT is an effective treatment for diabetic foot ulcers, decompression sickness in divers, and other conditions, such as cognitive impairment after stroke,” Marina Leitman, MD, of the Sackler School of Medicine, Tel Aviv, said in an interview. Her team also studied HBOT in asymptomatic older patients and found that the treatment seemed to improve left ventricular end systolic function.
“We should open our minds to thinking about this treatment for another indication,” she said. “That is the basis of precision medicine. We have this treatment and know it can be effective for cardiac pathology.
“Now we can say that post-COVID syndrome patients probably should be evaluated with echocardiography and GLS, which is the main parameter that showed improvement in our study,” she added. “If GLS is below normal values, these patients can benefit from HBOT, although additional research is needed to determine the optimal number of sessions.”
Dr. Leitman presented the study at the European Association of Cardiovascular Imaging 2023, a scientific congress of the European Society of Cardiology.
Biomarker changes
The study enrolled 60 hospitalized and nonhospitalized post-COVID syndrome patients with ongoing symptoms for at least 3 months after having mild to moderate symptomatic COVID-19.
Participants were randomized to receive HBOT or a sham procedure five times per week for 8 weeks, for a total of 40 sessions. They underwent echocardiography at baseline and 1-3 weeks after the final session to assess GLS.
The HBOT group received 100% oxygen through a mask at a pressure of two atmospheres for 90 minutes, with 5-minute air breaks every 20 minutes.
The sham group received 21% oxygen by mask at one atmosphere for 90 minutes.
At baseline, 29 participants (48%) had reduced GLS, despite having a normal ejection fraction, Dr. Leitman said. Of those, 16 (53%) were in the HBOT group and 13 (43%) were in the sham group.
The average GLS at baseline across all participants was –17.8%; a normal value is about –20%.
In the HBOT group, GLS increased significantly from –17.8% at baseline to –20.2% after HBOT. In the sham group, GLS was –17.8% at baseline and –19.1% at the end of the study, with no statistically significant difference between the two measurements.
In addition, GWE increased overall after HBOT from 96.3 to 97.1.
Dr. Leitman’s poster showed GLS and myocardial work indices before and after HBOT in a 45-year-old patient. Prior to treatment, GLS was –19%; GWE was 96%; and GWI was 1,833 mm Hg.
After HBOT treatment, GLS was –22%; GWE, 98%; and GWI, 1,911 mm Hg.
Clinical relevance unclear
Scott Gorenstein, MD, associate professor in the department of surgery and medical director of wound care and hyperbaric medicine at NYU Langone–Long Island, New York, commented on the study for this news organization.
“The approach certainly warrants studying, but the benefit is difficult to assess,” he said. “We still don’t understand the mechanism of long COVID, so it’s difficult to go from there to say that HBOT will be an effective therapy.”
That said, he added, “This is probably the best study I’ve seen in that it’s a randomized controlled trial, rather than a case series.”
Nevertheless, he noted, “We have no idea from this study whether the change in GLS is clinically relevant. As a clinician, I can’t now say that HBOT is going to improve heart failure secondary to long COVID. We don’t know whether the participants were New York heart failure class 3 or 4, for example, and all of a sudden went from really sick to really good.”
“There are many interventions that may change markers of cardiac function or inflammation,” he said. “But if they don’t make a difference in quantity or quality of life, is the treatment really valuable?”
Dr. Gorenstein said he would have no problem treating a patient with mild to moderate COVID-related heart failure with HBOT, since his own team’s study conducted near the outset of the pandemic showed it was safe. “But HBOT is an expensive treatment in the U.S. and there still are some risks and side effects, albeit very, very low.”
The study received no funding. Dr. Leitman and Dr. Gorenstein have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Patients with reduced left ventricular global longitudinal strain (GLS) at baseline who received HBOT had a significant increase in GLS, compared with those who received sham treatment.
GLS is a measure of systolic function that is thought to be a predictor of heart failure–related outcomes.
The study also showed that global work efficiency (GWE) and the global work index (GWI) increased in HBOT-treated patients, though not significantly.
“HBOT is an effective treatment for diabetic foot ulcers, decompression sickness in divers, and other conditions, such as cognitive impairment after stroke,” Marina Leitman, MD, of the Sackler School of Medicine, Tel Aviv, said in an interview. Her team also studied HBOT in asymptomatic older patients and found that the treatment seemed to improve left ventricular end systolic function.
“We should open our minds to thinking about this treatment for another indication,” she said. “That is the basis of precision medicine. We have this treatment and know it can be effective for cardiac pathology.
“Now we can say that post-COVID syndrome patients probably should be evaluated with echocardiography and GLS, which is the main parameter that showed improvement in our study,” she added. “If GLS is below normal values, these patients can benefit from HBOT, although additional research is needed to determine the optimal number of sessions.”
Dr. Leitman presented the study at the European Association of Cardiovascular Imaging 2023, a scientific congress of the European Society of Cardiology.
Biomarker changes
The study enrolled 60 hospitalized and nonhospitalized post-COVID syndrome patients with ongoing symptoms for at least 3 months after having mild to moderate symptomatic COVID-19.
Participants were randomized to receive HBOT or a sham procedure five times per week for 8 weeks, for a total of 40 sessions. They underwent echocardiography at baseline and 1-3 weeks after the final session to assess GLS.
The HBOT group received 100% oxygen through a mask at a pressure of two atmospheres for 90 minutes, with 5-minute air breaks every 20 minutes.
The sham group received 21% oxygen by mask at one atmosphere for 90 minutes.
At baseline, 29 participants (48%) had reduced GLS, despite having a normal ejection fraction, Dr. Leitman said. Of those, 16 (53%) were in the HBOT group and 13 (43%) were in the sham group.
The average GLS at baseline across all participants was –17.8%; a normal value is about –20%.
In the HBOT group, GLS increased significantly from –17.8% at baseline to –20.2% after HBOT. In the sham group, GLS was –17.8% at baseline and –19.1% at the end of the study, with no statistically significant difference between the two measurements.
In addition, GWE increased overall after HBOT from 96.3 to 97.1.
Dr. Leitman’s poster showed GLS and myocardial work indices before and after HBOT in a 45-year-old patient. Prior to treatment, GLS was –19%; GWE was 96%; and GWI was 1,833 mm Hg.
After HBOT treatment, GLS was –22%; GWE, 98%; and GWI, 1,911 mm Hg.
Clinical relevance unclear
Scott Gorenstein, MD, associate professor in the department of surgery and medical director of wound care and hyperbaric medicine at NYU Langone–Long Island, New York, commented on the study for this news organization.
“The approach certainly warrants studying, but the benefit is difficult to assess,” he said. “We still don’t understand the mechanism of long COVID, so it’s difficult to go from there to say that HBOT will be an effective therapy.”
That said, he added, “This is probably the best study I’ve seen in that it’s a randomized controlled trial, rather than a case series.”
Nevertheless, he noted, “We have no idea from this study whether the change in GLS is clinically relevant. As a clinician, I can’t now say that HBOT is going to improve heart failure secondary to long COVID. We don’t know whether the participants were New York heart failure class 3 or 4, for example, and all of a sudden went from really sick to really good.”
“There are many interventions that may change markers of cardiac function or inflammation,” he said. “But if they don’t make a difference in quantity or quality of life, is the treatment really valuable?”
Dr. Gorenstein said he would have no problem treating a patient with mild to moderate COVID-related heart failure with HBOT, since his own team’s study conducted near the outset of the pandemic showed it was safe. “But HBOT is an expensive treatment in the U.S. and there still are some risks and side effects, albeit very, very low.”
The study received no funding. Dr. Leitman and Dr. Gorenstein have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Patients with reduced left ventricular global longitudinal strain (GLS) at baseline who received HBOT had a significant increase in GLS, compared with those who received sham treatment.
GLS is a measure of systolic function that is thought to be a predictor of heart failure–related outcomes.
The study also showed that global work efficiency (GWE) and the global work index (GWI) increased in HBOT-treated patients, though not significantly.
“HBOT is an effective treatment for diabetic foot ulcers, decompression sickness in divers, and other conditions, such as cognitive impairment after stroke,” Marina Leitman, MD, of the Sackler School of Medicine, Tel Aviv, said in an interview. Her team also studied HBOT in asymptomatic older patients and found that the treatment seemed to improve left ventricular end systolic function.
“We should open our minds to thinking about this treatment for another indication,” she said. “That is the basis of precision medicine. We have this treatment and know it can be effective for cardiac pathology.
“Now we can say that post-COVID syndrome patients probably should be evaluated with echocardiography and GLS, which is the main parameter that showed improvement in our study,” she added. “If GLS is below normal values, these patients can benefit from HBOT, although additional research is needed to determine the optimal number of sessions.”
Dr. Leitman presented the study at the European Association of Cardiovascular Imaging 2023, a scientific congress of the European Society of Cardiology.
Biomarker changes
The study enrolled 60 hospitalized and nonhospitalized post-COVID syndrome patients with ongoing symptoms for at least 3 months after having mild to moderate symptomatic COVID-19.
Participants were randomized to receive HBOT or a sham procedure five times per week for 8 weeks, for a total of 40 sessions. They underwent echocardiography at baseline and 1-3 weeks after the final session to assess GLS.
The HBOT group received 100% oxygen through a mask at a pressure of two atmospheres for 90 minutes, with 5-minute air breaks every 20 minutes.
The sham group received 21% oxygen by mask at one atmosphere for 90 minutes.
At baseline, 29 participants (48%) had reduced GLS, despite having a normal ejection fraction, Dr. Leitman said. Of those, 16 (53%) were in the HBOT group and 13 (43%) were in the sham group.
The average GLS at baseline across all participants was –17.8%; a normal value is about –20%.
In the HBOT group, GLS increased significantly from –17.8% at baseline to –20.2% after HBOT. In the sham group, GLS was –17.8% at baseline and –19.1% at the end of the study, with no statistically significant difference between the two measurements.
In addition, GWE increased overall after HBOT from 96.3 to 97.1.
Dr. Leitman’s poster showed GLS and myocardial work indices before and after HBOT in a 45-year-old patient. Prior to treatment, GLS was –19%; GWE was 96%; and GWI was 1,833 mm Hg.
After HBOT treatment, GLS was –22%; GWE, 98%; and GWI, 1,911 mm Hg.
Clinical relevance unclear
Scott Gorenstein, MD, associate professor in the department of surgery and medical director of wound care and hyperbaric medicine at NYU Langone–Long Island, New York, commented on the study for this news organization.
“The approach certainly warrants studying, but the benefit is difficult to assess,” he said. “We still don’t understand the mechanism of long COVID, so it’s difficult to go from there to say that HBOT will be an effective therapy.”
That said, he added, “This is probably the best study I’ve seen in that it’s a randomized controlled trial, rather than a case series.”
Nevertheless, he noted, “We have no idea from this study whether the change in GLS is clinically relevant. As a clinician, I can’t now say that HBOT is going to improve heart failure secondary to long COVID. We don’t know whether the participants were New York heart failure class 3 or 4, for example, and all of a sudden went from really sick to really good.”
“There are many interventions that may change markers of cardiac function or inflammation,” he said. “But if they don’t make a difference in quantity or quality of life, is the treatment really valuable?”
Dr. Gorenstein said he would have no problem treating a patient with mild to moderate COVID-related heart failure with HBOT, since his own team’s study conducted near the outset of the pandemic showed it was safe. “But HBOT is an expensive treatment in the U.S. and there still are some risks and side effects, albeit very, very low.”
The study received no funding. Dr. Leitman and Dr. Gorenstein have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EACVI 2023
Risk for breast cancer reduced after bariatric surgery
In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.
The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”
The study was published online in JAMA Surgery.
Protective association
To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).
Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.
Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).
In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.
Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.
Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.
There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).
In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).
“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.
Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”
There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
A universal benefit?
“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.
“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.
“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”
Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”
The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”
At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”
The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.
The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”
The study was published online in JAMA Surgery.
Protective association
To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).
Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.
Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).
In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.
Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.
Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.
There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).
In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).
“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.
Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”
There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
A universal benefit?
“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.
“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.
“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”
Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”
The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”
At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”
The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.
The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”
The study was published online in JAMA Surgery.
Protective association
To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).
Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.
Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).
In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.
Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.
Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.
There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).
In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).
“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.
Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”
There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
A universal benefit?
“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.
“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.
“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”
Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”
The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”
At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”
The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA SURGERY
Risk assessment first urged for fragility fracture screening
A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.
To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.
The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.
Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.
The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.
“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.
“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
New evidence
“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”
To conduct the risk assessment in older women, clinicians are advised to do the following:
- Use the decision aid (which patients can also use on their own).
- Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
- If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.
Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.
“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”
“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”
To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
Other at-risk groups?
Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.
“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.
For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”
A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.
Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.
To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.
The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.
Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.
The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.
“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.
“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
New evidence
“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”
To conduct the risk assessment in older women, clinicians are advised to do the following:
- Use the decision aid (which patients can also use on their own).
- Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
- If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.
Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.
“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”
“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”
To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
Other at-risk groups?
Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.
“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.
For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”
A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.
Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new Canadian guideline on screening for the primary prevention of fragility fractures recommends risk assessment first, before bone mineral density (BMD) testing, for women aged 65 and older. For younger women and men aged 40 and older, screening is not recommended.
To develop the guideline, a writing group from Canadian Task Force on Preventive Health Care commissioned systematic reviews of studies on the benefits and harms of fragility fracture screenings; the predictive accuracy of current risk-assessment tools; patient acceptability; and benefits of treatment. Treatment harms were analyzed via a rapid overview of reviews.
The guideline, published online in the Canadian Medical Association Journal, is aimed at primary care practitioners for their community-dwelling patients aged 40 and older. The recommendations do not apply to people already taking preventive drugs.
Nondrug treatments were beyond the scope of the current guideline, but guidelines on the prevention of falls and other strategies are planned, Roland Grad, MD, a guideline author and associate professor at McGill University in Montreal, told this news organization.
The new guideline says that women aged 65 and older may be able to avoid fracture through screening and preventive medication. An individual’s fracture risk can be estimated with a new Fragility Fractures Decision Aid, which uses the Canadian FRAX risk-assessment tool.
“A risk assessment–first approach promotes shared decision-making with the patient, based on best medical evidence,” Dr. Grad said.
“To help clinicians, we have created an infographic with visuals to communicate the time spent on BMD vs risk assessment first.”
New evidence
“At least three things motivated this new guideline,” Dr. Grad said. “When we started work on this prior to the pandemic, we saw a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of screening trials in females older than 65.”
To conduct the risk assessment in older women, clinicians are advised to do the following:
- Use the decision aid (which patients can also use on their own).
- Use the 10-year absolute risk of major osteoporotic fracture to facilitate shared decision-making about possible benefits and harms of preventive pharmacotherapy.
- If pharmacotherapy is being considered, request a BMD using DXA of the femoral neck, then reestimate the fracture risk by adding the BMD T-score into the FRAX.
Potential harms associated with various treatments, with varying levels of evidence, include the following: with alendronate and denosumab, nonserious gastrointestinal adverse events; with denosumab, rash, eczema, and infections; with zoledronic acid, nonserious events, such as headache and flulike symptoms; and with alendronate and bisphosphonates, rare but serious harms of atypical femoral fracture and osteonecrosis of the jaw.
“These recommendations emphasize the importance of good clinical practice, where clinicians are alert to changes in physical health and patient well-being,” the authors wrote. “Clinicians should also be aware of the importance of secondary prevention (i.e., after fracture) and manage patients accordingly.”
“This is an important topic,” Dr. Grad said. “Fragility fractures are consequential for individuals and for our publicly funded health care system. We anticipate questions from clinicians about the time needed to screen with the risk assessment–first strategy. Our modeling work suggests time savings with [this] strategy compared to a strategy of BMD testing first. Following our recommendations may lead to a reduction in BMD testing.”
To promote the guideline, the CMAJ has recorded a podcast and will use other strategies to increase awareness, Dr. Grad said. “The Canadian Task Force has a communications strategy that includes outreach to primary care, stakeholder webinars, social media, partnerships, and other tactics. The College of Family Physicians of Canada has endorsed the guideline and will help promote to its members.”
Other at-risk groups?
Aliya Khan, MD, FRCPC, FACP, FACE, professor in the divisions of endocrinology and metabolism and geriatrics and director of the fellowship in metabolic bone diseases at McMaster University in Hamilton, Ont., told this news organization she agrees with the strategy of evaluating women aged 65 and older for fracture risk.
“The decision aid is useful, but I would like to see it expanded to other circumstances and situations,” she said.
For example, Dr. Khan would like to see recommendations for younger women and for men of all ages regarding secondary causes of osteoporosis or medications known to have a detrimental effect on bone health. By not addressing these patients, she said, “we may miss patients who would benefit from a fracture risk assessment and potentially treatment to prevent low-trauma fractures.”
A recommendation for younger postmenopausal women was included in the most recent Society of Obstetricians and Gynaecologists Canada guideline, she noted.
Overall, she said, “I believe these recommendations will reduce the excess or inappropriate use of BMD testing and that is welcome.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. The task force members report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Virtual care not linked with greater ED use during pandemic
Canadian family physicians’ increased use of virtual care during the first years of the pandemic was not associated with increased emergency department use among patients, a new analysis of data from Ontario suggests.
In a cross-sectional study that included almost 14,000 family physicians and almost 13 million patients in Ontario, an adjusted analysis indicated that patients with physicians who provided more than 20% of care virtually had lower rates of ED visits, compared with patients whose physicians provided the least virtual care.
“I was surprised to see that ED visit volumes in fall 2021 were below prepandemic levels,” study author Tara Kiran, MD, who practices family medicine at St. Michael’s Hospital of the University of Toronto, told this news organization.
“At that time, there was a lot in the news about how our EDs were overcrowded and an assumption that this related to higher visit volumes. But our data [suggest] there were other factors at play, including strains in staffing in the ED, hospital inpatient units, and in long-term care.” Dr. Kiran is also the Fidani chair in improvement and innovation and vice-chair of quality and innovation at the department of family and community medicine of the University of Toronto.
The study was published online in JAMA Network Open.
Embrace of telehealth
The investigators analyzed administrative data from Ontario for 13,820 family physicians (mean age, 50 years; 51.5% men) and 12,951,063 patients (mean age, 42.6 years; 51.8% women) under their care.
The family physicians had at least one primary care visit claim between Feb. 1 and Oct. 31, 2021. The researchers categorized the physicians by the percentage of total visits they delivered virtually (via telephone or video) during the study period, as follows: 0% (100% in person), greater than 0%-20%, greater than 20%-40%, greater than 40%-60%, greater than 60%-80%, greater than 80% to less than 100%, or 100%.
The percentage of virtual primary care visits peaked at 82% in the first 2 weeks of the pandemic and decreased to 49% by October 2021. ED visit rates decreased at the start of the pandemic and remained lower than in 2019 throughout the study period.
Most physicians provided between 40% and 80% of care virtually. A greater percentage of those who provided more than 80% of care virtually were aged 65 years or older, were women, and practiced in large cities.
Patient comorbidity and morbidity were similar across all categories of virtual care use. The mean number of ED visits was highest among patients whose physicians provided only in-person care (470.3 per 1,000 patients) and was lowest among those whose physicians provided greater than 0% to less than 100% of care virtually (242 per 1,000 patients).
After adjustment for patient characteristics, patients of physicians who provided more than 20% of care virtually had lower rates of ED visits, compared with patients of physicians who provided the least virtual care (for example, greater than 80% to less than 100% versus 0%-20% virtual visits in big cities; relative rate, 0.77). This pattern was consistent across all rurality of practice categories and after adjustment for 2019 ED visit rates.
The investigators observed a gradient in urban areas. Patients of physicians who provided the highest level of virtual care had the lowest ED visit rates.
Investigating virtual modalities
Some policymakers worried that inappropriate use of virtual care was leading to an increase in ED use. “Findings of this study refute this hypothesis,” the authors write. Increases in ED use seemed to coincide with decreases in COVID-19 cases, not with increases in virtual primary care visits.
Furthermore, at the population level, patients who were cared for by physicians who provided a high percentage of virtual care did not have a higher rate of ED visits, compared with those cared for by physicians who provided the lowest levels of virtual care.
During the pandemic, the switch to virtual care worked well for some of Dr. Kiran’s patients. It was more convenient, because they didn’t have to take time off work, travel to and from the clinic, find and pay for parking, or wait in the clinic before the appointment, she said.
But for others, “virtual care really didn’t work well,” she said. “This was particularly true for people who didn’t have a regular working phone, who didn’t have a private space to take calls, who weren’t fluent in English, and who were hard of hearing or had severe mental illness that resulted in paranoid thoughts.”
Clinicians also may have had different comfort levels and preferences regarding virtual visits, Dr. Kiran hypothesized. Some found it convenient and efficient, whereas others may have found it cumbersome and inefficient. “I personally find it harder to build relationships with patients when I use virtual care,” she said. “I experience more joy in work with in-person visits, but other clinicians may feel differently.”
Dr. Kiran and her colleagues are conducting a public engagement initiative called OurCare to understand public perspectives on the future of primary care. “As part of that work, we want to understand what virtual modalities are most important to the public and how the public thinks these should be integrated into primary care.”
Virtual care can support access, patient-centered care, and equity in primary care, Dr. Kiran added. “Ideally, it should be integrated into an existing relationship with a family physician and be a complement to in-person visits.”
The right dose?
In an accompanying editorial, Jesse M. Pines, MD, chief of clinical innovation at U.S. Acute Care Solutions, Canton, Ohio, writes, “There is no convincing mechanism consistent with the data for the observed outcome of lower ED use at higher telehealth use.”
Additional research is needed, he notes, to answer the “Goldilocks question” – that is, what amount of telehealth optimizes its benefits while minimizing potential problems?
“The right dose of telehealth needs to balance (1) concerns by payers and policymakers that it will increase cost and cause unintended consequences (for example, misdiagnosis or duplicative care) and (2) the desire of its proponents who want to allow clinicians to use it as they see fit, with few restrictions,” writes Dr. Pines.
“Future research would ideally use more robust research design,” he suggested. “For example, randomized trials could test different doses of telehealth, or mixed-methods studies could help elucidate how telehealth may be changing clinical management or care-seeking behavior.”
Equitable reimbursement needed
Priya Nori, MD, associate professor of infectious diseases at Montefiore Health System and associate professor at the Albert Einstein College of Medicine, both in New York, said, “I agree with their conclusions and am reassured about telehealth as a durable form of health care delivery.”
Large, population-level studies such as this one might persuade legislators to require equitable reimbursement for in-person and virtual visits “so providers have comparable incentives to provide both types of care,” she said. “Although only primary care was addressed in the study, I believe that virtual care is here to stay and can be applied to primary care, subspecialty care, and other services, like antimicrobial stewardship, infection prevention, et cetera. We need to embrace it.”
A similar study should be conducted in the United States, along with additional research “to ensure that visits done by telephone have similar outcomes as those done by video, as not all communities have adequate internet access or video conferencing technology,” said Dr. Nori.
The study was supported by ICES and grants from Ontario Health, the Canadian Institutes of Health Research, and the Health Systems Research Program of Ontario MOH. Dr. Kiran, Dr. Pines, and Dr. Nori have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Canadian family physicians’ increased use of virtual care during the first years of the pandemic was not associated with increased emergency department use among patients, a new analysis of data from Ontario suggests.
In a cross-sectional study that included almost 14,000 family physicians and almost 13 million patients in Ontario, an adjusted analysis indicated that patients with physicians who provided more than 20% of care virtually had lower rates of ED visits, compared with patients whose physicians provided the least virtual care.
“I was surprised to see that ED visit volumes in fall 2021 were below prepandemic levels,” study author Tara Kiran, MD, who practices family medicine at St. Michael’s Hospital of the University of Toronto, told this news organization.
“At that time, there was a lot in the news about how our EDs were overcrowded and an assumption that this related to higher visit volumes. But our data [suggest] there were other factors at play, including strains in staffing in the ED, hospital inpatient units, and in long-term care.” Dr. Kiran is also the Fidani chair in improvement and innovation and vice-chair of quality and innovation at the department of family and community medicine of the University of Toronto.
The study was published online in JAMA Network Open.
Embrace of telehealth
The investigators analyzed administrative data from Ontario for 13,820 family physicians (mean age, 50 years; 51.5% men) and 12,951,063 patients (mean age, 42.6 years; 51.8% women) under their care.
The family physicians had at least one primary care visit claim between Feb. 1 and Oct. 31, 2021. The researchers categorized the physicians by the percentage of total visits they delivered virtually (via telephone or video) during the study period, as follows: 0% (100% in person), greater than 0%-20%, greater than 20%-40%, greater than 40%-60%, greater than 60%-80%, greater than 80% to less than 100%, or 100%.
The percentage of virtual primary care visits peaked at 82% in the first 2 weeks of the pandemic and decreased to 49% by October 2021. ED visit rates decreased at the start of the pandemic and remained lower than in 2019 throughout the study period.
Most physicians provided between 40% and 80% of care virtually. A greater percentage of those who provided more than 80% of care virtually were aged 65 years or older, were women, and practiced in large cities.
Patient comorbidity and morbidity were similar across all categories of virtual care use. The mean number of ED visits was highest among patients whose physicians provided only in-person care (470.3 per 1,000 patients) and was lowest among those whose physicians provided greater than 0% to less than 100% of care virtually (242 per 1,000 patients).
After adjustment for patient characteristics, patients of physicians who provided more than 20% of care virtually had lower rates of ED visits, compared with patients of physicians who provided the least virtual care (for example, greater than 80% to less than 100% versus 0%-20% virtual visits in big cities; relative rate, 0.77). This pattern was consistent across all rurality of practice categories and after adjustment for 2019 ED visit rates.
The investigators observed a gradient in urban areas. Patients of physicians who provided the highest level of virtual care had the lowest ED visit rates.
Investigating virtual modalities
Some policymakers worried that inappropriate use of virtual care was leading to an increase in ED use. “Findings of this study refute this hypothesis,” the authors write. Increases in ED use seemed to coincide with decreases in COVID-19 cases, not with increases in virtual primary care visits.
Furthermore, at the population level, patients who were cared for by physicians who provided a high percentage of virtual care did not have a higher rate of ED visits, compared with those cared for by physicians who provided the lowest levels of virtual care.
During the pandemic, the switch to virtual care worked well for some of Dr. Kiran’s patients. It was more convenient, because they didn’t have to take time off work, travel to and from the clinic, find and pay for parking, or wait in the clinic before the appointment, she said.
But for others, “virtual care really didn’t work well,” she said. “This was particularly true for people who didn’t have a regular working phone, who didn’t have a private space to take calls, who weren’t fluent in English, and who were hard of hearing or had severe mental illness that resulted in paranoid thoughts.”
Clinicians also may have had different comfort levels and preferences regarding virtual visits, Dr. Kiran hypothesized. Some found it convenient and efficient, whereas others may have found it cumbersome and inefficient. “I personally find it harder to build relationships with patients when I use virtual care,” she said. “I experience more joy in work with in-person visits, but other clinicians may feel differently.”
Dr. Kiran and her colleagues are conducting a public engagement initiative called OurCare to understand public perspectives on the future of primary care. “As part of that work, we want to understand what virtual modalities are most important to the public and how the public thinks these should be integrated into primary care.”
Virtual care can support access, patient-centered care, and equity in primary care, Dr. Kiran added. “Ideally, it should be integrated into an existing relationship with a family physician and be a complement to in-person visits.”
The right dose?
In an accompanying editorial, Jesse M. Pines, MD, chief of clinical innovation at U.S. Acute Care Solutions, Canton, Ohio, writes, “There is no convincing mechanism consistent with the data for the observed outcome of lower ED use at higher telehealth use.”
Additional research is needed, he notes, to answer the “Goldilocks question” – that is, what amount of telehealth optimizes its benefits while minimizing potential problems?
“The right dose of telehealth needs to balance (1) concerns by payers and policymakers that it will increase cost and cause unintended consequences (for example, misdiagnosis or duplicative care) and (2) the desire of its proponents who want to allow clinicians to use it as they see fit, with few restrictions,” writes Dr. Pines.
“Future research would ideally use more robust research design,” he suggested. “For example, randomized trials could test different doses of telehealth, or mixed-methods studies could help elucidate how telehealth may be changing clinical management or care-seeking behavior.”
Equitable reimbursement needed
Priya Nori, MD, associate professor of infectious diseases at Montefiore Health System and associate professor at the Albert Einstein College of Medicine, both in New York, said, “I agree with their conclusions and am reassured about telehealth as a durable form of health care delivery.”
Large, population-level studies such as this one might persuade legislators to require equitable reimbursement for in-person and virtual visits “so providers have comparable incentives to provide both types of care,” she said. “Although only primary care was addressed in the study, I believe that virtual care is here to stay and can be applied to primary care, subspecialty care, and other services, like antimicrobial stewardship, infection prevention, et cetera. We need to embrace it.”
A similar study should be conducted in the United States, along with additional research “to ensure that visits done by telephone have similar outcomes as those done by video, as not all communities have adequate internet access or video conferencing technology,” said Dr. Nori.
The study was supported by ICES and grants from Ontario Health, the Canadian Institutes of Health Research, and the Health Systems Research Program of Ontario MOH. Dr. Kiran, Dr. Pines, and Dr. Nori have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Canadian family physicians’ increased use of virtual care during the first years of the pandemic was not associated with increased emergency department use among patients, a new analysis of data from Ontario suggests.
In a cross-sectional study that included almost 14,000 family physicians and almost 13 million patients in Ontario, an adjusted analysis indicated that patients with physicians who provided more than 20% of care virtually had lower rates of ED visits, compared with patients whose physicians provided the least virtual care.
“I was surprised to see that ED visit volumes in fall 2021 were below prepandemic levels,” study author Tara Kiran, MD, who practices family medicine at St. Michael’s Hospital of the University of Toronto, told this news organization.
“At that time, there was a lot in the news about how our EDs were overcrowded and an assumption that this related to higher visit volumes. But our data [suggest] there were other factors at play, including strains in staffing in the ED, hospital inpatient units, and in long-term care.” Dr. Kiran is also the Fidani chair in improvement and innovation and vice-chair of quality and innovation at the department of family and community medicine of the University of Toronto.
The study was published online in JAMA Network Open.
Embrace of telehealth
The investigators analyzed administrative data from Ontario for 13,820 family physicians (mean age, 50 years; 51.5% men) and 12,951,063 patients (mean age, 42.6 years; 51.8% women) under their care.
The family physicians had at least one primary care visit claim between Feb. 1 and Oct. 31, 2021. The researchers categorized the physicians by the percentage of total visits they delivered virtually (via telephone or video) during the study period, as follows: 0% (100% in person), greater than 0%-20%, greater than 20%-40%, greater than 40%-60%, greater than 60%-80%, greater than 80% to less than 100%, or 100%.
The percentage of virtual primary care visits peaked at 82% in the first 2 weeks of the pandemic and decreased to 49% by October 2021. ED visit rates decreased at the start of the pandemic and remained lower than in 2019 throughout the study period.
Most physicians provided between 40% and 80% of care virtually. A greater percentage of those who provided more than 80% of care virtually were aged 65 years or older, were women, and practiced in large cities.
Patient comorbidity and morbidity were similar across all categories of virtual care use. The mean number of ED visits was highest among patients whose physicians provided only in-person care (470.3 per 1,000 patients) and was lowest among those whose physicians provided greater than 0% to less than 100% of care virtually (242 per 1,000 patients).
After adjustment for patient characteristics, patients of physicians who provided more than 20% of care virtually had lower rates of ED visits, compared with patients of physicians who provided the least virtual care (for example, greater than 80% to less than 100% versus 0%-20% virtual visits in big cities; relative rate, 0.77). This pattern was consistent across all rurality of practice categories and after adjustment for 2019 ED visit rates.
The investigators observed a gradient in urban areas. Patients of physicians who provided the highest level of virtual care had the lowest ED visit rates.
Investigating virtual modalities
Some policymakers worried that inappropriate use of virtual care was leading to an increase in ED use. “Findings of this study refute this hypothesis,” the authors write. Increases in ED use seemed to coincide with decreases in COVID-19 cases, not with increases in virtual primary care visits.
Furthermore, at the population level, patients who were cared for by physicians who provided a high percentage of virtual care did not have a higher rate of ED visits, compared with those cared for by physicians who provided the lowest levels of virtual care.
During the pandemic, the switch to virtual care worked well for some of Dr. Kiran’s patients. It was more convenient, because they didn’t have to take time off work, travel to and from the clinic, find and pay for parking, or wait in the clinic before the appointment, she said.
But for others, “virtual care really didn’t work well,” she said. “This was particularly true for people who didn’t have a regular working phone, who didn’t have a private space to take calls, who weren’t fluent in English, and who were hard of hearing or had severe mental illness that resulted in paranoid thoughts.”
Clinicians also may have had different comfort levels and preferences regarding virtual visits, Dr. Kiran hypothesized. Some found it convenient and efficient, whereas others may have found it cumbersome and inefficient. “I personally find it harder to build relationships with patients when I use virtual care,” she said. “I experience more joy in work with in-person visits, but other clinicians may feel differently.”
Dr. Kiran and her colleagues are conducting a public engagement initiative called OurCare to understand public perspectives on the future of primary care. “As part of that work, we want to understand what virtual modalities are most important to the public and how the public thinks these should be integrated into primary care.”
Virtual care can support access, patient-centered care, and equity in primary care, Dr. Kiran added. “Ideally, it should be integrated into an existing relationship with a family physician and be a complement to in-person visits.”
The right dose?
In an accompanying editorial, Jesse M. Pines, MD, chief of clinical innovation at U.S. Acute Care Solutions, Canton, Ohio, writes, “There is no convincing mechanism consistent with the data for the observed outcome of lower ED use at higher telehealth use.”
Additional research is needed, he notes, to answer the “Goldilocks question” – that is, what amount of telehealth optimizes its benefits while minimizing potential problems?
“The right dose of telehealth needs to balance (1) concerns by payers and policymakers that it will increase cost and cause unintended consequences (for example, misdiagnosis or duplicative care) and (2) the desire of its proponents who want to allow clinicians to use it as they see fit, with few restrictions,” writes Dr. Pines.
“Future research would ideally use more robust research design,” he suggested. “For example, randomized trials could test different doses of telehealth, or mixed-methods studies could help elucidate how telehealth may be changing clinical management or care-seeking behavior.”
Equitable reimbursement needed
Priya Nori, MD, associate professor of infectious diseases at Montefiore Health System and associate professor at the Albert Einstein College of Medicine, both in New York, said, “I agree with their conclusions and am reassured about telehealth as a durable form of health care delivery.”
Large, population-level studies such as this one might persuade legislators to require equitable reimbursement for in-person and virtual visits “so providers have comparable incentives to provide both types of care,” she said. “Although only primary care was addressed in the study, I believe that virtual care is here to stay and can be applied to primary care, subspecialty care, and other services, like antimicrobial stewardship, infection prevention, et cetera. We need to embrace it.”
A similar study should be conducted in the United States, along with additional research “to ensure that visits done by telephone have similar outcomes as those done by video, as not all communities have adequate internet access or video conferencing technology,” said Dr. Nori.
The study was supported by ICES and grants from Ontario Health, the Canadian Institutes of Health Research, and the Health Systems Research Program of Ontario MOH. Dr. Kiran, Dr. Pines, and Dr. Nori have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.