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‘High normal’ sodium, poor hydration linked to heart failure
– a heart failure (HF) precursor – and for HF itself, in older age, a new study suggests.
Compared with middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study with normal serum sodium, those with levels of 142-146 mmol/L were more likely to have left ventricular hypertrophy or HF when they were in their 70s and 80s, independent of other risk factors.
Natalia Dmitrieva, PhD, a research scientist at the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md., presented the study findings in an e-poster on Aug. 27 at the European Society of Cardiology (ESC) Congress 2021.
“Our study suggests that maintaining good hydration can prevent or at least slow down the changes within the heart that lead to heart failure,” she said in a statement from the ESC.
It “suggests that all adults should aim for eight to ten glasses of liquid [daily] and keep salt intake low,” Dr. Dmitrieva said in an interview.
However, people should not rely completely on thirst, she cautioned, especially in middle age, when thirst sensation starts to deteriorate. And too much fluid intake can be harmful and even dangerous.
Normal serum sodium is usually defined as 135-146 mmol/L, Dr. Dmitrieva explained, and this study involved only patients in ARIC with sodium levels in this range, to try to exclude patients with genetic or water-salt balance diseases.
The findings suggest that a serum sodium level of 142-146 mmol/L, which would not be flagged as abnormal by a test lab, “can be used by clinicians as a warning sign” for a patient’s increased risk for HF, she noted.
Clinicians should explain this risk to patients and advise them to drink at least 2 L per day. However, people should not try to reduce their sodium levels by drinking more than 2 to 3 L per day, she cautioned, which can be harmful and even deadly, and they should consult their doctors.
Watch hydration
“An important finding of this study is that sodium values considered ‘normal’ may also be deleterious,” Jacob Joseph, MD, director, heart failure program, VA Boston Healthcare System, who was not involved with this study, said in an interview.
“These results are similar to studies we have conducted in heart failure with preserved ejection fraction,” noted Dr. Joseph, associate professor of medicine at Harvard Medical School, Boston.
Their studies showed a U-shaped relationship between serum sodium values and adverse outcomes, “indicating an ‘optimal’ range of serum sodium value that was narrower than the accepted normal laboratory value range,” he noted.
The study by Dmitrieva et al. was observational and the findings would need to be verified in a randomized controlled trial, Dr. Joseph pointed out; however, the research “supports the idea that even a high normal sodium level may indicate risk of future heart failure.
“Hence, patients should pay attention to hydration,” he continued, and “clinicians should not assume that a sodium level of 142 mmol/L is appropriate and should ensure that patients are paying attention to hydration.
“In today’s busy and stress-filled lifestyle, it is easy to forget about adequate fluid intake,” Dr. Joseph added.
More than 15,000 adults followed for 25 Years
To investigate the relationship between serum sodium, hydration, and future heart failure, Dr. Dmitrieva and colleagues analyzed data from 15,792 adults in ARIC who were 44-66 years of age at study entry, with serum sodium levels from 135 to 146 mmol/L.
The participants were evaluated over five visits until they reached 70-90 years.
They were divided into four groups based on their average serum sodium concentrations at study visits one and two (conducted in the first 3 years): 135 -139.5 mmol/L, 140-141.5 mmol/L, 142-143.5 mmol/L, and 144-146 mmol/L.
The researchers determined the percentage of people in each group who developed HF and left ventricular hypertrophy at visit five (25 years after study enrollment).
Patients with higher serum sodium levels had a significantly higher risk for HF and left ventricular hypertrophy, after adjustment for other risk factors, including age, blood pressure, kidney function, blood cholesterol, blood glucose, body mass index, sex, and smoking status.
Every 1 mmol/L increase in serum sodium concentration in midlife was associated with 1.20 and 1.11 increased odds of developing left ventricular hypertrophy and HF, respectively, 25 years later.
“More studies are needed to find out what proportion of people with serum sodium 142 mmol/L and higher have this [serum sodium] level because they do not drink enough and will be able to reduce it by making sure they consistently drink 2 to 2.5 L per day,” said Dr. Dmitrieva.
“It is likely that for some people, other factors that are related to genetics or diseases affecting water-salt balance could be causing their increased serum sodium levels,” she speculated.
The study was funded by the Intramural Program of the National Heart, Lung, and Blood Institute. The authors and Dr. Joseph have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
– a heart failure (HF) precursor – and for HF itself, in older age, a new study suggests.
Compared with middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study with normal serum sodium, those with levels of 142-146 mmol/L were more likely to have left ventricular hypertrophy or HF when they were in their 70s and 80s, independent of other risk factors.
Natalia Dmitrieva, PhD, a research scientist at the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md., presented the study findings in an e-poster on Aug. 27 at the European Society of Cardiology (ESC) Congress 2021.
“Our study suggests that maintaining good hydration can prevent or at least slow down the changes within the heart that lead to heart failure,” she said in a statement from the ESC.
It “suggests that all adults should aim for eight to ten glasses of liquid [daily] and keep salt intake low,” Dr. Dmitrieva said in an interview.
However, people should not rely completely on thirst, she cautioned, especially in middle age, when thirst sensation starts to deteriorate. And too much fluid intake can be harmful and even dangerous.
Normal serum sodium is usually defined as 135-146 mmol/L, Dr. Dmitrieva explained, and this study involved only patients in ARIC with sodium levels in this range, to try to exclude patients with genetic or water-salt balance diseases.
The findings suggest that a serum sodium level of 142-146 mmol/L, which would not be flagged as abnormal by a test lab, “can be used by clinicians as a warning sign” for a patient’s increased risk for HF, she noted.
Clinicians should explain this risk to patients and advise them to drink at least 2 L per day. However, people should not try to reduce their sodium levels by drinking more than 2 to 3 L per day, she cautioned, which can be harmful and even deadly, and they should consult their doctors.
Watch hydration
“An important finding of this study is that sodium values considered ‘normal’ may also be deleterious,” Jacob Joseph, MD, director, heart failure program, VA Boston Healthcare System, who was not involved with this study, said in an interview.
“These results are similar to studies we have conducted in heart failure with preserved ejection fraction,” noted Dr. Joseph, associate professor of medicine at Harvard Medical School, Boston.
Their studies showed a U-shaped relationship between serum sodium values and adverse outcomes, “indicating an ‘optimal’ range of serum sodium value that was narrower than the accepted normal laboratory value range,” he noted.
The study by Dmitrieva et al. was observational and the findings would need to be verified in a randomized controlled trial, Dr. Joseph pointed out; however, the research “supports the idea that even a high normal sodium level may indicate risk of future heart failure.
“Hence, patients should pay attention to hydration,” he continued, and “clinicians should not assume that a sodium level of 142 mmol/L is appropriate and should ensure that patients are paying attention to hydration.
“In today’s busy and stress-filled lifestyle, it is easy to forget about adequate fluid intake,” Dr. Joseph added.
More than 15,000 adults followed for 25 Years
To investigate the relationship between serum sodium, hydration, and future heart failure, Dr. Dmitrieva and colleagues analyzed data from 15,792 adults in ARIC who were 44-66 years of age at study entry, with serum sodium levels from 135 to 146 mmol/L.
The participants were evaluated over five visits until they reached 70-90 years.
They were divided into four groups based on their average serum sodium concentrations at study visits one and two (conducted in the first 3 years): 135 -139.5 mmol/L, 140-141.5 mmol/L, 142-143.5 mmol/L, and 144-146 mmol/L.
The researchers determined the percentage of people in each group who developed HF and left ventricular hypertrophy at visit five (25 years after study enrollment).
Patients with higher serum sodium levels had a significantly higher risk for HF and left ventricular hypertrophy, after adjustment for other risk factors, including age, blood pressure, kidney function, blood cholesterol, blood glucose, body mass index, sex, and smoking status.
Every 1 mmol/L increase in serum sodium concentration in midlife was associated with 1.20 and 1.11 increased odds of developing left ventricular hypertrophy and HF, respectively, 25 years later.
“More studies are needed to find out what proportion of people with serum sodium 142 mmol/L and higher have this [serum sodium] level because they do not drink enough and will be able to reduce it by making sure they consistently drink 2 to 2.5 L per day,” said Dr. Dmitrieva.
“It is likely that for some people, other factors that are related to genetics or diseases affecting water-salt balance could be causing their increased serum sodium levels,” she speculated.
The study was funded by the Intramural Program of the National Heart, Lung, and Blood Institute. The authors and Dr. Joseph have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
– a heart failure (HF) precursor – and for HF itself, in older age, a new study suggests.
Compared with middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study with normal serum sodium, those with levels of 142-146 mmol/L were more likely to have left ventricular hypertrophy or HF when they were in their 70s and 80s, independent of other risk factors.
Natalia Dmitrieva, PhD, a research scientist at the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md., presented the study findings in an e-poster on Aug. 27 at the European Society of Cardiology (ESC) Congress 2021.
“Our study suggests that maintaining good hydration can prevent or at least slow down the changes within the heart that lead to heart failure,” she said in a statement from the ESC.
It “suggests that all adults should aim for eight to ten glasses of liquid [daily] and keep salt intake low,” Dr. Dmitrieva said in an interview.
However, people should not rely completely on thirst, she cautioned, especially in middle age, when thirst sensation starts to deteriorate. And too much fluid intake can be harmful and even dangerous.
Normal serum sodium is usually defined as 135-146 mmol/L, Dr. Dmitrieva explained, and this study involved only patients in ARIC with sodium levels in this range, to try to exclude patients with genetic or water-salt balance diseases.
The findings suggest that a serum sodium level of 142-146 mmol/L, which would not be flagged as abnormal by a test lab, “can be used by clinicians as a warning sign” for a patient’s increased risk for HF, she noted.
Clinicians should explain this risk to patients and advise them to drink at least 2 L per day. However, people should not try to reduce their sodium levels by drinking more than 2 to 3 L per day, she cautioned, which can be harmful and even deadly, and they should consult their doctors.
Watch hydration
“An important finding of this study is that sodium values considered ‘normal’ may also be deleterious,” Jacob Joseph, MD, director, heart failure program, VA Boston Healthcare System, who was not involved with this study, said in an interview.
“These results are similar to studies we have conducted in heart failure with preserved ejection fraction,” noted Dr. Joseph, associate professor of medicine at Harvard Medical School, Boston.
Their studies showed a U-shaped relationship between serum sodium values and adverse outcomes, “indicating an ‘optimal’ range of serum sodium value that was narrower than the accepted normal laboratory value range,” he noted.
The study by Dmitrieva et al. was observational and the findings would need to be verified in a randomized controlled trial, Dr. Joseph pointed out; however, the research “supports the idea that even a high normal sodium level may indicate risk of future heart failure.
“Hence, patients should pay attention to hydration,” he continued, and “clinicians should not assume that a sodium level of 142 mmol/L is appropriate and should ensure that patients are paying attention to hydration.
“In today’s busy and stress-filled lifestyle, it is easy to forget about adequate fluid intake,” Dr. Joseph added.
More than 15,000 adults followed for 25 Years
To investigate the relationship between serum sodium, hydration, and future heart failure, Dr. Dmitrieva and colleagues analyzed data from 15,792 adults in ARIC who were 44-66 years of age at study entry, with serum sodium levels from 135 to 146 mmol/L.
The participants were evaluated over five visits until they reached 70-90 years.
They were divided into four groups based on their average serum sodium concentrations at study visits one and two (conducted in the first 3 years): 135 -139.5 mmol/L, 140-141.5 mmol/L, 142-143.5 mmol/L, and 144-146 mmol/L.
The researchers determined the percentage of people in each group who developed HF and left ventricular hypertrophy at visit five (25 years after study enrollment).
Patients with higher serum sodium levels had a significantly higher risk for HF and left ventricular hypertrophy, after adjustment for other risk factors, including age, blood pressure, kidney function, blood cholesterol, blood glucose, body mass index, sex, and smoking status.
Every 1 mmol/L increase in serum sodium concentration in midlife was associated with 1.20 and 1.11 increased odds of developing left ventricular hypertrophy and HF, respectively, 25 years later.
“More studies are needed to find out what proportion of people with serum sodium 142 mmol/L and higher have this [serum sodium] level because they do not drink enough and will be able to reduce it by making sure they consistently drink 2 to 2.5 L per day,” said Dr. Dmitrieva.
“It is likely that for some people, other factors that are related to genetics or diseases affecting water-salt balance could be causing their increased serum sodium levels,” she speculated.
The study was funded by the Intramural Program of the National Heart, Lung, and Blood Institute. The authors and Dr. Joseph have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Coffee drinking in midlife tied to heart benefits
Among middle-aged people without heart disease, drinking up to three cups of coffee per day was linked with a lower risk for stroke or death over the next decade, along with better heart structure and function, in a large, observational study.
Specifically, light-to-moderate coffee drinking, defined as 0.5 to 3 cups per day, was associated with a 21% lower risk for stroke, a 17% lower risk for death from cardiovascular disease (CVD), and a 12% lower risk for death from all causes, as well as more favorable cardiac MRI findings, compared with nondrinkers (< 0.5 cup per day) during a median 11-year follow-up.
Heavy coffee drinkers, defined as those consuming more than three cups per day, on the other hand, likewise had more favorable cardiac MRI findings, but with similar (not lower) rates of stroke and CVD or all-cause mortality compared with nondrinkers.
Judit Simon, MD, presented these findings, from close to 500,000 participants in the UK Biobank study, at a press conference before an e-poster session at the virtual annual congress of the European Society of Cardiology.
“To our knowledge, this is the largest study to systematically assess the cardiovascular effects of regular coffee consumption in a population without diagnosed heart disease,” Dr. Simon, a PhD student at the Heart and Vascular Centre, Semmelweis University, Budapest, Hungary, said in an ESC press release.
The results “suggest that regular coffee consumption is safe, as even high daily intake was not associated with adverse cardiovascular outcomes and all-cause mortality after a follow-up of 10 to 15 years,” she said.
The imaging analysis showed that “compared with participants who did not drink coffee regularly, daily consumers had healthier sized and better functioning hearts,” Dr. Simon continued, “consistent with reversing the detrimental effects of aging on the heart.”
“The observed benefits might be partly explained by positive alterations in cardiac structure and function,” she speculated, adding that further studies are needed to explain the underlying mechanisms.
Instant coffee most popular
In this population, the coffee drinkers mostly drank instant coffee (55%), followed by filtered/ground (23%), decaffeinated (20%), or other types of coffee (2%), Dr. Simon said in an interview.
Risk for myocardial infarction (MI) or heart failure did not significantly differ for different categories of coffee intake, she added. The researchers did not study the effect of coffee consumption on atrial fibrillation (AF), she noted.
Study limitations, Dr. Simon acknowledged, include that it was observational, so it cannot show causation, and that coffee consumption was self-reported in a questionnaire.
Invited to comment, Alice H. Lichtenstein, DSc, who was not involved with the research, said, “Consistent with prior data, this new study indicates there is no adverse effect of coffee consumption on cardiovascular health and there may be a benefit.”
However, “because of the nature of the data, it would not be recommended that an individual starting drinking coffee to improve cardiovascular health,” added Dr. Lichtenstein, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston.
But if people already drink coffee, “it is fine to continue, assuming that the coffee drinks are not high in added sugar and cream,” she said in an interview.
Coffee intake, CVD outcomes, and heart structure
To study the relationship between coffee intake and incident MI, stroke, and death, as well as heart structure, the researchers examined data from the UK Biobank, which recruited 500,000 people aged 40-69 years in 2006-2010 from across the United Kingdom.
They identified 468,629 participants with no signs of heart disease at recruitment and an average age of 56 years, of whom 56% were women.
The participants were divided into three groups based on usual coffee intake: none (22% of participants), light-to-moderate (58%), and high (20%).
Median tea intake was three cups per day overall, four cups per day in noncoffee drinkers, three cups per day in light-to-moderate coffee drinkers, and one cup per day in high coffee drinkers.
Compared to not drinking coffee, light-to-moderate coffee consumption was associated with lower risks for all-cause death (hazard ratio [HR], 0.88; P < .001), CVD death (HR, 0.83; P = .006), and stroke (HR, 0.79; P = .037), over a median follow-up of 11 years, after adjustment for sex; weight; height; smoking status; physical activity; high blood pressure; diabetes; cholesterol level; socioeconomic status; and usual intake of alcohol, meat, tea, fruit, and vegetables.
In the 30,650 participants who had cardiac MRI data, the study found that compared with not drinking coffee, both light-to-moderate and high coffee consumption were associated with significantly increased left and right ventricular end-systolic and end-diastolic volumes, and with greater left ventricular mass (all P < .001).
These differences were small but significant, Dr. Simon stressed, because this was a cohort of healthy patients who did not have CVD (heart failure, MI, stroke, AF) at baseline, although some had hypertension or diabetes.
Press conference chairperson, Steen Dalby Kristensen, MD, professor and cardiologist, Aarhus University Hospital, Denmark, a coffee lover himself, wanted to know if an amount such as two, three, or four cups of coffee was optimal to see these heart benefits, and whether there were differences in benefits seen with drinking different types of coffee.
The analysis did not identify an optimal coffee intake, Dr. Simon said. Compared with not drinking coffee, she continued, drinking instant coffee was associated with a lower risk for all-cause mortality, but not CVD mortality or stroke.
Drinking filtered coffee was associated with lower risks for all three outcomes, but there was no significant difference in risk for MI. Drinking decaffeinated coffee was associated with a lower risk for all-cause and CVD mortality.
“Decaffeinated coffee contains a small amount of caffeine,” Dr. Simon pointed out. “Something other than caffeine might have this protective impact,” she suggested.
The researchers and Dr. Lichtenstein declared having no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Among middle-aged people without heart disease, drinking up to three cups of coffee per day was linked with a lower risk for stroke or death over the next decade, along with better heart structure and function, in a large, observational study.
Specifically, light-to-moderate coffee drinking, defined as 0.5 to 3 cups per day, was associated with a 21% lower risk for stroke, a 17% lower risk for death from cardiovascular disease (CVD), and a 12% lower risk for death from all causes, as well as more favorable cardiac MRI findings, compared with nondrinkers (< 0.5 cup per day) during a median 11-year follow-up.
Heavy coffee drinkers, defined as those consuming more than three cups per day, on the other hand, likewise had more favorable cardiac MRI findings, but with similar (not lower) rates of stroke and CVD or all-cause mortality compared with nondrinkers.
Judit Simon, MD, presented these findings, from close to 500,000 participants in the UK Biobank study, at a press conference before an e-poster session at the virtual annual congress of the European Society of Cardiology.
“To our knowledge, this is the largest study to systematically assess the cardiovascular effects of regular coffee consumption in a population without diagnosed heart disease,” Dr. Simon, a PhD student at the Heart and Vascular Centre, Semmelweis University, Budapest, Hungary, said in an ESC press release.
The results “suggest that regular coffee consumption is safe, as even high daily intake was not associated with adverse cardiovascular outcomes and all-cause mortality after a follow-up of 10 to 15 years,” she said.
The imaging analysis showed that “compared with participants who did not drink coffee regularly, daily consumers had healthier sized and better functioning hearts,” Dr. Simon continued, “consistent with reversing the detrimental effects of aging on the heart.”
“The observed benefits might be partly explained by positive alterations in cardiac structure and function,” she speculated, adding that further studies are needed to explain the underlying mechanisms.
Instant coffee most popular
In this population, the coffee drinkers mostly drank instant coffee (55%), followed by filtered/ground (23%), decaffeinated (20%), or other types of coffee (2%), Dr. Simon said in an interview.
Risk for myocardial infarction (MI) or heart failure did not significantly differ for different categories of coffee intake, she added. The researchers did not study the effect of coffee consumption on atrial fibrillation (AF), she noted.
Study limitations, Dr. Simon acknowledged, include that it was observational, so it cannot show causation, and that coffee consumption was self-reported in a questionnaire.
Invited to comment, Alice H. Lichtenstein, DSc, who was not involved with the research, said, “Consistent with prior data, this new study indicates there is no adverse effect of coffee consumption on cardiovascular health and there may be a benefit.”
However, “because of the nature of the data, it would not be recommended that an individual starting drinking coffee to improve cardiovascular health,” added Dr. Lichtenstein, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston.
But if people already drink coffee, “it is fine to continue, assuming that the coffee drinks are not high in added sugar and cream,” she said in an interview.
Coffee intake, CVD outcomes, and heart structure
To study the relationship between coffee intake and incident MI, stroke, and death, as well as heart structure, the researchers examined data from the UK Biobank, which recruited 500,000 people aged 40-69 years in 2006-2010 from across the United Kingdom.
They identified 468,629 participants with no signs of heart disease at recruitment and an average age of 56 years, of whom 56% were women.
The participants were divided into three groups based on usual coffee intake: none (22% of participants), light-to-moderate (58%), and high (20%).
Median tea intake was three cups per day overall, four cups per day in noncoffee drinkers, three cups per day in light-to-moderate coffee drinkers, and one cup per day in high coffee drinkers.
Compared to not drinking coffee, light-to-moderate coffee consumption was associated with lower risks for all-cause death (hazard ratio [HR], 0.88; P < .001), CVD death (HR, 0.83; P = .006), and stroke (HR, 0.79; P = .037), over a median follow-up of 11 years, after adjustment for sex; weight; height; smoking status; physical activity; high blood pressure; diabetes; cholesterol level; socioeconomic status; and usual intake of alcohol, meat, tea, fruit, and vegetables.
In the 30,650 participants who had cardiac MRI data, the study found that compared with not drinking coffee, both light-to-moderate and high coffee consumption were associated with significantly increased left and right ventricular end-systolic and end-diastolic volumes, and with greater left ventricular mass (all P < .001).
These differences were small but significant, Dr. Simon stressed, because this was a cohort of healthy patients who did not have CVD (heart failure, MI, stroke, AF) at baseline, although some had hypertension or diabetes.
Press conference chairperson, Steen Dalby Kristensen, MD, professor and cardiologist, Aarhus University Hospital, Denmark, a coffee lover himself, wanted to know if an amount such as two, three, or four cups of coffee was optimal to see these heart benefits, and whether there were differences in benefits seen with drinking different types of coffee.
The analysis did not identify an optimal coffee intake, Dr. Simon said. Compared with not drinking coffee, she continued, drinking instant coffee was associated with a lower risk for all-cause mortality, but not CVD mortality or stroke.
Drinking filtered coffee was associated with lower risks for all three outcomes, but there was no significant difference in risk for MI. Drinking decaffeinated coffee was associated with a lower risk for all-cause and CVD mortality.
“Decaffeinated coffee contains a small amount of caffeine,” Dr. Simon pointed out. “Something other than caffeine might have this protective impact,” she suggested.
The researchers and Dr. Lichtenstein declared having no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Among middle-aged people without heart disease, drinking up to three cups of coffee per day was linked with a lower risk for stroke or death over the next decade, along with better heart structure and function, in a large, observational study.
Specifically, light-to-moderate coffee drinking, defined as 0.5 to 3 cups per day, was associated with a 21% lower risk for stroke, a 17% lower risk for death from cardiovascular disease (CVD), and a 12% lower risk for death from all causes, as well as more favorable cardiac MRI findings, compared with nondrinkers (< 0.5 cup per day) during a median 11-year follow-up.
Heavy coffee drinkers, defined as those consuming more than three cups per day, on the other hand, likewise had more favorable cardiac MRI findings, but with similar (not lower) rates of stroke and CVD or all-cause mortality compared with nondrinkers.
Judit Simon, MD, presented these findings, from close to 500,000 participants in the UK Biobank study, at a press conference before an e-poster session at the virtual annual congress of the European Society of Cardiology.
“To our knowledge, this is the largest study to systematically assess the cardiovascular effects of regular coffee consumption in a population without diagnosed heart disease,” Dr. Simon, a PhD student at the Heart and Vascular Centre, Semmelweis University, Budapest, Hungary, said in an ESC press release.
The results “suggest that regular coffee consumption is safe, as even high daily intake was not associated with adverse cardiovascular outcomes and all-cause mortality after a follow-up of 10 to 15 years,” she said.
The imaging analysis showed that “compared with participants who did not drink coffee regularly, daily consumers had healthier sized and better functioning hearts,” Dr. Simon continued, “consistent with reversing the detrimental effects of aging on the heart.”
“The observed benefits might be partly explained by positive alterations in cardiac structure and function,” she speculated, adding that further studies are needed to explain the underlying mechanisms.
Instant coffee most popular
In this population, the coffee drinkers mostly drank instant coffee (55%), followed by filtered/ground (23%), decaffeinated (20%), or other types of coffee (2%), Dr. Simon said in an interview.
Risk for myocardial infarction (MI) or heart failure did not significantly differ for different categories of coffee intake, she added. The researchers did not study the effect of coffee consumption on atrial fibrillation (AF), she noted.
Study limitations, Dr. Simon acknowledged, include that it was observational, so it cannot show causation, and that coffee consumption was self-reported in a questionnaire.
Invited to comment, Alice H. Lichtenstein, DSc, who was not involved with the research, said, “Consistent with prior data, this new study indicates there is no adverse effect of coffee consumption on cardiovascular health and there may be a benefit.”
However, “because of the nature of the data, it would not be recommended that an individual starting drinking coffee to improve cardiovascular health,” added Dr. Lichtenstein, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston.
But if people already drink coffee, “it is fine to continue, assuming that the coffee drinks are not high in added sugar and cream,” she said in an interview.
Coffee intake, CVD outcomes, and heart structure
To study the relationship between coffee intake and incident MI, stroke, and death, as well as heart structure, the researchers examined data from the UK Biobank, which recruited 500,000 people aged 40-69 years in 2006-2010 from across the United Kingdom.
They identified 468,629 participants with no signs of heart disease at recruitment and an average age of 56 years, of whom 56% were women.
The participants were divided into three groups based on usual coffee intake: none (22% of participants), light-to-moderate (58%), and high (20%).
Median tea intake was three cups per day overall, four cups per day in noncoffee drinkers, three cups per day in light-to-moderate coffee drinkers, and one cup per day in high coffee drinkers.
Compared to not drinking coffee, light-to-moderate coffee consumption was associated with lower risks for all-cause death (hazard ratio [HR], 0.88; P < .001), CVD death (HR, 0.83; P = .006), and stroke (HR, 0.79; P = .037), over a median follow-up of 11 years, after adjustment for sex; weight; height; smoking status; physical activity; high blood pressure; diabetes; cholesterol level; socioeconomic status; and usual intake of alcohol, meat, tea, fruit, and vegetables.
In the 30,650 participants who had cardiac MRI data, the study found that compared with not drinking coffee, both light-to-moderate and high coffee consumption were associated with significantly increased left and right ventricular end-systolic and end-diastolic volumes, and with greater left ventricular mass (all P < .001).
These differences were small but significant, Dr. Simon stressed, because this was a cohort of healthy patients who did not have CVD (heart failure, MI, stroke, AF) at baseline, although some had hypertension or diabetes.
Press conference chairperson, Steen Dalby Kristensen, MD, professor and cardiologist, Aarhus University Hospital, Denmark, a coffee lover himself, wanted to know if an amount such as two, three, or four cups of coffee was optimal to see these heart benefits, and whether there were differences in benefits seen with drinking different types of coffee.
The analysis did not identify an optimal coffee intake, Dr. Simon said. Compared with not drinking coffee, she continued, drinking instant coffee was associated with a lower risk for all-cause mortality, but not CVD mortality or stroke.
Drinking filtered coffee was associated with lower risks for all three outcomes, but there was no significant difference in risk for MI. Drinking decaffeinated coffee was associated with a lower risk for all-cause and CVD mortality.
“Decaffeinated coffee contains a small amount of caffeine,” Dr. Simon pointed out. “Something other than caffeine might have this protective impact,” she suggested.
The researchers and Dr. Lichtenstein declared having no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
APAF-CRT: ‘Ablate and pace’ cuts mortality in narrow-QRS HF, permanent AFib
When a patient has permanent atrial fibrillation (AFib) and advanced heart failure (HF), rate control therapy is an option but an “ablate-and-pace” strategy may be better at improving symptoms. The ablate-and-pace approach, compared to pharmacologic rate control, may even prolong survival in a subset of such patients when the accompanying pacemaker provides cardiac resynchronization therapy (CRT), suggests a new randomized trial.
In the APAF-CRT trial, mortality fell more than 70% over 4 years for such patients with HF and narrow QRS intervals who were assigned to ablate-and-pace – that is, CRT after creation of heart block by atrioventricular (AV) junction ablation – compared to those managed medically.
The benefit was seen regardless of left ventricular ejection fraction (LVEF) at the start of the trial and probably stemmed from “the combination of strict rate control and rate regulation achieved by AV-junction ablation together with biventricular pacing,” said Michele Brignole, MD, Istituto Auxologico Italiano, Ospedale San Luca, Milan. The CRT substitution for a standard pacemaker, he explained, is thought to “counteract” the adverse remodeling effects of apical right ventricular (RV) pacing.
Dr. Brignole delivered the remarks at a media presentation before his presentation of the APAF-CRT during the virtual annual congress of the European Society of Cardiology.
The results “support ablation-CRT as a first-line therapy in patients with permanent AFib and narrow QRS who were hospitalized for heart failure,” regardless of ejection fraction, said Dr. Brignole, lead author on the study’s same-day publication in the European Heart Journal.
“The results are not surprising. They are in line with prior studies with shorter follow-up, and they justify a relatively common practice today, to implant CRT in these patients. It has previously been shown to improve heart failure and quality of life, and is now proven to improve survival because of the longer follow-up,” Michael Glikson, MD, Shaare Zedek Medical Center, Jerusalem, said at the media briefing.
“The APAF-CRT mortality trial makes an important contribution to establishment of AV-nodal ablation with CRT as first-line therapy of resistant atrial fibrillation with heart failure, mostly in patients with reduced ejection fraction,” said Dr. Glikson, who was not part of the trial.
However, he added, “the advantage of CRT over RV pacing is still somewhat unclear in patients with normal or preserved ejection fraction,” who were relatively few in APAF-CRT and in whom RV apical pacing after AV nodal ablation has not been shown to make a big difference to ventricular function.
The new analysis covered the trial’s second phase, which featured a mortality primary endpoint, in contrast to the previously reported initial stage that followed the first 102 patients over 2 years for death, worsening HF, or HF hospitalization.
The first phase had halted enrollment before reaching its planned target of 280 patients when an interim analysis showed a significant benefit for ablate and pace. The mortality trial continued to recruit at 11 centers in Europe, reaching 133 patients, who were followed for up to 4 years, the report notes. But its enrollment had also been suspended after an interim analysis saw superiority in the ablate-and-pace arm.
APAF-CRT entered patients with severely symptomatic permanent AFib for longer than 6 months, with a QRS interval no greater than 110 ms, who had at least one HF hospitalization in the last year and were considered poor candidates for AFib ablation. Their mean age was 73 years, and almost half, 47%, were women.
They were randomly assigned to ablate-and-pace with CRT or pharmacologic rate control therapy, 63 and 70 patients, respectively. Patients in either group could be given an implantable defibrillator at physician discretion.
Patients had been followed a median of 29 months when the trial was stopped for efficacy. The hazard ratio (HR) for death from any cause, ablate-and-pace vs. rate control, was 0.26 (95% confidence interval, 0.10-0.65; P = .004), with a number needed to treat to prevent an event of 3.7. The HR was 0.40 (95% CI, 0.22-0.73; P = .002) for the secondary endpoint of death or HF hospitalization.
The new ESC guidelines on cardiac pacing and cardiac resynchronization therapy recommend “that if the ejection fraction is subnormal, they should receive a CRT as the first choice,” Dr. Glikson said. “However, for patients who are undergoing AV nodal ablation and have normal ejection fractions, we thought that RV apical pacing should be okay,” so that was the main recommendation, he said.
“I think that the APAF-CRT study does not really change this approach” because the study was small and there were few data on such patients.
APAF-CRT was an investigator-initiated independent clinical trial, sponsored by a nonprofit organization, Centro Prevenzione Malattie Cardiorespiratorie ‘Nuccia e Vittore Corbella’, Rapallo, Italy, which received an unrestricted research grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee. Dr. Brignole declared no conflicts. Disclosures for the other authors are in the report. Dr. Glikson had no disclosures.
A version of this article first appeared on Medscape.com.
When a patient has permanent atrial fibrillation (AFib) and advanced heart failure (HF), rate control therapy is an option but an “ablate-and-pace” strategy may be better at improving symptoms. The ablate-and-pace approach, compared to pharmacologic rate control, may even prolong survival in a subset of such patients when the accompanying pacemaker provides cardiac resynchronization therapy (CRT), suggests a new randomized trial.
In the APAF-CRT trial, mortality fell more than 70% over 4 years for such patients with HF and narrow QRS intervals who were assigned to ablate-and-pace – that is, CRT after creation of heart block by atrioventricular (AV) junction ablation – compared to those managed medically.
The benefit was seen regardless of left ventricular ejection fraction (LVEF) at the start of the trial and probably stemmed from “the combination of strict rate control and rate regulation achieved by AV-junction ablation together with biventricular pacing,” said Michele Brignole, MD, Istituto Auxologico Italiano, Ospedale San Luca, Milan. The CRT substitution for a standard pacemaker, he explained, is thought to “counteract” the adverse remodeling effects of apical right ventricular (RV) pacing.
Dr. Brignole delivered the remarks at a media presentation before his presentation of the APAF-CRT during the virtual annual congress of the European Society of Cardiology.
The results “support ablation-CRT as a first-line therapy in patients with permanent AFib and narrow QRS who were hospitalized for heart failure,” regardless of ejection fraction, said Dr. Brignole, lead author on the study’s same-day publication in the European Heart Journal.
“The results are not surprising. They are in line with prior studies with shorter follow-up, and they justify a relatively common practice today, to implant CRT in these patients. It has previously been shown to improve heart failure and quality of life, and is now proven to improve survival because of the longer follow-up,” Michael Glikson, MD, Shaare Zedek Medical Center, Jerusalem, said at the media briefing.
“The APAF-CRT mortality trial makes an important contribution to establishment of AV-nodal ablation with CRT as first-line therapy of resistant atrial fibrillation with heart failure, mostly in patients with reduced ejection fraction,” said Dr. Glikson, who was not part of the trial.
However, he added, “the advantage of CRT over RV pacing is still somewhat unclear in patients with normal or preserved ejection fraction,” who were relatively few in APAF-CRT and in whom RV apical pacing after AV nodal ablation has not been shown to make a big difference to ventricular function.
The new analysis covered the trial’s second phase, which featured a mortality primary endpoint, in contrast to the previously reported initial stage that followed the first 102 patients over 2 years for death, worsening HF, or HF hospitalization.
The first phase had halted enrollment before reaching its planned target of 280 patients when an interim analysis showed a significant benefit for ablate and pace. The mortality trial continued to recruit at 11 centers in Europe, reaching 133 patients, who were followed for up to 4 years, the report notes. But its enrollment had also been suspended after an interim analysis saw superiority in the ablate-and-pace arm.
APAF-CRT entered patients with severely symptomatic permanent AFib for longer than 6 months, with a QRS interval no greater than 110 ms, who had at least one HF hospitalization in the last year and were considered poor candidates for AFib ablation. Their mean age was 73 years, and almost half, 47%, were women.
They were randomly assigned to ablate-and-pace with CRT or pharmacologic rate control therapy, 63 and 70 patients, respectively. Patients in either group could be given an implantable defibrillator at physician discretion.
Patients had been followed a median of 29 months when the trial was stopped for efficacy. The hazard ratio (HR) for death from any cause, ablate-and-pace vs. rate control, was 0.26 (95% confidence interval, 0.10-0.65; P = .004), with a number needed to treat to prevent an event of 3.7. The HR was 0.40 (95% CI, 0.22-0.73; P = .002) for the secondary endpoint of death or HF hospitalization.
The new ESC guidelines on cardiac pacing and cardiac resynchronization therapy recommend “that if the ejection fraction is subnormal, they should receive a CRT as the first choice,” Dr. Glikson said. “However, for patients who are undergoing AV nodal ablation and have normal ejection fractions, we thought that RV apical pacing should be okay,” so that was the main recommendation, he said.
“I think that the APAF-CRT study does not really change this approach” because the study was small and there were few data on such patients.
APAF-CRT was an investigator-initiated independent clinical trial, sponsored by a nonprofit organization, Centro Prevenzione Malattie Cardiorespiratorie ‘Nuccia e Vittore Corbella’, Rapallo, Italy, which received an unrestricted research grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee. Dr. Brignole declared no conflicts. Disclosures for the other authors are in the report. Dr. Glikson had no disclosures.
A version of this article first appeared on Medscape.com.
When a patient has permanent atrial fibrillation (AFib) and advanced heart failure (HF), rate control therapy is an option but an “ablate-and-pace” strategy may be better at improving symptoms. The ablate-and-pace approach, compared to pharmacologic rate control, may even prolong survival in a subset of such patients when the accompanying pacemaker provides cardiac resynchronization therapy (CRT), suggests a new randomized trial.
In the APAF-CRT trial, mortality fell more than 70% over 4 years for such patients with HF and narrow QRS intervals who were assigned to ablate-and-pace – that is, CRT after creation of heart block by atrioventricular (AV) junction ablation – compared to those managed medically.
The benefit was seen regardless of left ventricular ejection fraction (LVEF) at the start of the trial and probably stemmed from “the combination of strict rate control and rate regulation achieved by AV-junction ablation together with biventricular pacing,” said Michele Brignole, MD, Istituto Auxologico Italiano, Ospedale San Luca, Milan. The CRT substitution for a standard pacemaker, he explained, is thought to “counteract” the adverse remodeling effects of apical right ventricular (RV) pacing.
Dr. Brignole delivered the remarks at a media presentation before his presentation of the APAF-CRT during the virtual annual congress of the European Society of Cardiology.
The results “support ablation-CRT as a first-line therapy in patients with permanent AFib and narrow QRS who were hospitalized for heart failure,” regardless of ejection fraction, said Dr. Brignole, lead author on the study’s same-day publication in the European Heart Journal.
“The results are not surprising. They are in line with prior studies with shorter follow-up, and they justify a relatively common practice today, to implant CRT in these patients. It has previously been shown to improve heart failure and quality of life, and is now proven to improve survival because of the longer follow-up,” Michael Glikson, MD, Shaare Zedek Medical Center, Jerusalem, said at the media briefing.
“The APAF-CRT mortality trial makes an important contribution to establishment of AV-nodal ablation with CRT as first-line therapy of resistant atrial fibrillation with heart failure, mostly in patients with reduced ejection fraction,” said Dr. Glikson, who was not part of the trial.
However, he added, “the advantage of CRT over RV pacing is still somewhat unclear in patients with normal or preserved ejection fraction,” who were relatively few in APAF-CRT and in whom RV apical pacing after AV nodal ablation has not been shown to make a big difference to ventricular function.
The new analysis covered the trial’s second phase, which featured a mortality primary endpoint, in contrast to the previously reported initial stage that followed the first 102 patients over 2 years for death, worsening HF, or HF hospitalization.
The first phase had halted enrollment before reaching its planned target of 280 patients when an interim analysis showed a significant benefit for ablate and pace. The mortality trial continued to recruit at 11 centers in Europe, reaching 133 patients, who were followed for up to 4 years, the report notes. But its enrollment had also been suspended after an interim analysis saw superiority in the ablate-and-pace arm.
APAF-CRT entered patients with severely symptomatic permanent AFib for longer than 6 months, with a QRS interval no greater than 110 ms, who had at least one HF hospitalization in the last year and were considered poor candidates for AFib ablation. Their mean age was 73 years, and almost half, 47%, were women.
They were randomly assigned to ablate-and-pace with CRT or pharmacologic rate control therapy, 63 and 70 patients, respectively. Patients in either group could be given an implantable defibrillator at physician discretion.
Patients had been followed a median of 29 months when the trial was stopped for efficacy. The hazard ratio (HR) for death from any cause, ablate-and-pace vs. rate control, was 0.26 (95% confidence interval, 0.10-0.65; P = .004), with a number needed to treat to prevent an event of 3.7. The HR was 0.40 (95% CI, 0.22-0.73; P = .002) for the secondary endpoint of death or HF hospitalization.
The new ESC guidelines on cardiac pacing and cardiac resynchronization therapy recommend “that if the ejection fraction is subnormal, they should receive a CRT as the first choice,” Dr. Glikson said. “However, for patients who are undergoing AV nodal ablation and have normal ejection fractions, we thought that RV apical pacing should be okay,” so that was the main recommendation, he said.
“I think that the APAF-CRT study does not really change this approach” because the study was small and there were few data on such patients.
APAF-CRT was an investigator-initiated independent clinical trial, sponsored by a nonprofit organization, Centro Prevenzione Malattie Cardiorespiratorie ‘Nuccia e Vittore Corbella’, Rapallo, Italy, which received an unrestricted research grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee. Dr. Brignole declared no conflicts. Disclosures for the other authors are in the report. Dr. Glikson had no disclosures.
A version of this article first appeared on Medscape.com.
FIDELITY: Finerenone benefits patients with T2D across CKD spectrum
New data on using the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone to treat patients with type 2 diabetes and chronic kidney disease did more than further confirm this new drug’s efficacy in these patients for slowing progression to end-stage renal disease and reducing hospitalizations for heart failure.
It also strengthened the case for clinicians to be much more proactive in collecting urine specimens from patients with type 2 diabetes (T2D) to find those with albuminuria whose kidney function has not yet dropped below 60 mL/min per 1.73 m2, a population that the data show finerenone can help.
The FIDELITY prespecified meta-analysis combined data from two related pivotal trials of finerenone (Kerendia) in a total of more than 13,000 patients with T2D and chronic kidney disease (CKD). Each of these two trials, FIDELIO-DKD and FIGARO-DKD, identified patients with CKD by either of two methods, or a total of four different criteria.
In sum, the two trials enrolled patients with an estimated glomerular filtration rate (eGFR) of 25-90 mL/min per 1.73 m2 and a urinary albumin-to-creatinine ratio (UACR) of 30-299, or an eGFR of 25-75 mL/min per 1.73 m2 and a UACR of 300-5,000. The result was that 40% of enrolled patients had an eGFR of at least 60, levels that are considered normal, but they also had some level of albuminuria that defined them as having CKD.
The results showed that during a median follow-up of 36 months, patients with a normal eGFR and albuminuria had their combined incidence of cardiovascular disease events (cardiovascular death, MI, stroke, or hospitalization for heart failure) reduced by roughly the same amount as seen in patients with lower levels of eGFR and renal function, a finding that reimagines how clinicians need to routinely screen patients with T2D for CKD, Gerasimos Filippatos, MD, reported at the virtual annual congress of the European Society of Cardiology.
“Measuring UACR in patients with type 2 diabetes is important to identify patients who will benefit from finerenone treatment independent of their eGFR,” said Dr. Filippatos, professor of medicine at the University of Athens and director of the heart failure unit at Attikon University Hospital in Athens.
The combined FIDELITY analysis showed a significant overall cut in the combined cardiovascular disease endpoint of 14% relative to placebo, which reflected a 1.7% absolute reduction in events between the two arms during 3 years of treatment. The primary driver of this benefit was the significant drop in hospitalizations for heart failure on finerenone compared with placebo, which fell by a relative 22% and by an absolute 1.1%, Dr. Filippatos reported.
Routinely screening for albuminuria is ‘practice changing’
“This is really practice changing information for cardiologists,” said Rajiv L. Agarwal, MD, a copresenter of the FIDELITY analysis and a lead investigator of the two finerenone trials.
When cardiologists and possibly other specialists see patients with T2D, they traditionally have focused on measuring left ventricular ejection fraction and checking for other indications of heart failure. The new results from FIDELIO-DKD and FIGARO-DKD showed that finerenone treatment can prevent heart failure onset or worsening in patients with T2D with finerenone, which clinicians can accomplish by “simply measuring UACR,” as well as eGFR, and then treating patients with abnormal levels of either, explained Dr. Agarwal, a nephrologist and professor of medicine at Indiana University in Indianapolis.
“Diabetologists know that when they see patients with diabetes they need to collect a urine sample to check for albuminuria. But when some other clinicians see a patient with type 2 diabetes and a normal eGFR, they often think that the patient is okay and don’t get a urine specimen,” noted Bertram Pitt, MD, another collaborator of the finerenone trials and a heart failure specialist affiliated with the University of Michigan in Ann Arbor.
“We need to pay more attention to UACR and albuminuria; traditionally clinicians have mostly looked at eGFR,” agreed Dipti Itchhaporia, MD, a cardiologist at the Carlton Heart and Vascular Institute of Hoag Hospital in Newport Beach, Calif. UACR “is a marker that should be shared” between endocrinologists, nephrologists, and cardiologists as they together care for patients with T2D, suggested Dr. Itchhaporia, president of the American College of Cardiology.
Two pivotal trials with consistent findings
The FIDELITY analysis combined data from the FIDELIO-DKD trial, reported in 2020, and from the FIGARO-DKD trial that was first reported during the current congress as well as in a simultaneous report published online.
Results from the two trials were very consistent, although the primary endpoint in FIDELIO-DKD was a composite measure of renal disease with the combined cardiovascular disease metric a secondary endpoint, while this got flipped in FIGARO-DKD which had the cardiovascular disease composite as its primary endpoint as the combined renal outcomes as a secondary endpoint.
In addition to showing a consistent, significant reduction in both combined cardiovascular disease events and in the specific endpoint of hospitalization for heart failure, the two trials also showed a consistent benefit for slowing renal disease progression, including significantly fewer patients developing end-stage kidney disease. In the combined FIDELITY analysis, treatment with finerenone cut the incidence of end-stage kidney disease by a significant 20% compared with placebo, and by an absolute reduction of 0.6%.
Another common finding was a relatively low incidence of hyperkalemia compared with what’s usually seen using a steroidal MRA, spironolactone or eplerenone. In the combined analysis treatment with finerenone produced a 14% incidence of any hyperkalemia compared with 7% among placebo-treated patients, and the rate of patients stopping their treatment because of hyperkalemia was 1.7% on finerenone and 0.6% on placebo.
“Finerenone is much better tolerated” than the steroidal MRAs in causing clinically significant hyperkalemia, noted Dr. Pitt. “There are a lot of misconceptions” about the potassium-raising potential of MRAs, and “people get frightened” by the potential. Spreading the message of finerenone’s relative safety “will take a lot of education,” he acknowledged. Routine monitoring of potassium levels is a key step to minimizing the risk for hyperkalemia when using finerenone, he added.
Suggested benefit from combination treatment
Another intriguing observation from FIDELITY derived from the fact that roughly 7% of enrolled patients were also on treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor at entry, and about 7% were on treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, and in both subgroups the incidence of the composite cardiovascular disease endpoint appeared to suggest additive effects of agents from either of these classes when combined with finerenone. Although the numbers of patients on combined treatment were too low to show a definitive result, “our expectation is that we will see an additive effect,” said Dr. Pitt. Ideally, patients with T2D and CKD “should be on both” an SGLT2 inhibitor and finerenone, he predicted.
SGLT2 inhibitors have now been embraced as a key treatment for patients with T2D or with heart failure with reduced ejection fraction, and the preliminary data suggest that combining these agents with finerenone can provide additional benefit, agreed Dr. Itchhaporia. Aside from the need for more evidence to prove this, there are also practical considerations of “How do we pay for all these fantastic therapies?” She expressed optimism that cost-benefit analyses will eventually show that the additive benefits justify the added cost.
Based largely on results from FIDELIO-DKD, finerenone received marketing approval from the Food and Drug Administration in July 2021 for the indication of treating patients with T2D and chronic kidney disease.
FIGARO-DKD, FIDELIO-DKD, and FIDELITY were sponsored by Bayer, the company that markets finerenone. Dr. Filippatos has received lecture fees from Bayer, and has had financial relationships with Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Agarwal received travel support from and has been a consultant to Bayer and to numerous other companies. Dr. Pitt has been a consultant to Bayer and to numerous other companies. Dr. Itchhaporia had no disclosures.
New data on using the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone to treat patients with type 2 diabetes and chronic kidney disease did more than further confirm this new drug’s efficacy in these patients for slowing progression to end-stage renal disease and reducing hospitalizations for heart failure.
It also strengthened the case for clinicians to be much more proactive in collecting urine specimens from patients with type 2 diabetes (T2D) to find those with albuminuria whose kidney function has not yet dropped below 60 mL/min per 1.73 m2, a population that the data show finerenone can help.
The FIDELITY prespecified meta-analysis combined data from two related pivotal trials of finerenone (Kerendia) in a total of more than 13,000 patients with T2D and chronic kidney disease (CKD). Each of these two trials, FIDELIO-DKD and FIGARO-DKD, identified patients with CKD by either of two methods, or a total of four different criteria.
In sum, the two trials enrolled patients with an estimated glomerular filtration rate (eGFR) of 25-90 mL/min per 1.73 m2 and a urinary albumin-to-creatinine ratio (UACR) of 30-299, or an eGFR of 25-75 mL/min per 1.73 m2 and a UACR of 300-5,000. The result was that 40% of enrolled patients had an eGFR of at least 60, levels that are considered normal, but they also had some level of albuminuria that defined them as having CKD.
The results showed that during a median follow-up of 36 months, patients with a normal eGFR and albuminuria had their combined incidence of cardiovascular disease events (cardiovascular death, MI, stroke, or hospitalization for heart failure) reduced by roughly the same amount as seen in patients with lower levels of eGFR and renal function, a finding that reimagines how clinicians need to routinely screen patients with T2D for CKD, Gerasimos Filippatos, MD, reported at the virtual annual congress of the European Society of Cardiology.
“Measuring UACR in patients with type 2 diabetes is important to identify patients who will benefit from finerenone treatment independent of their eGFR,” said Dr. Filippatos, professor of medicine at the University of Athens and director of the heart failure unit at Attikon University Hospital in Athens.
The combined FIDELITY analysis showed a significant overall cut in the combined cardiovascular disease endpoint of 14% relative to placebo, which reflected a 1.7% absolute reduction in events between the two arms during 3 years of treatment. The primary driver of this benefit was the significant drop in hospitalizations for heart failure on finerenone compared with placebo, which fell by a relative 22% and by an absolute 1.1%, Dr. Filippatos reported.
Routinely screening for albuminuria is ‘practice changing’
“This is really practice changing information for cardiologists,” said Rajiv L. Agarwal, MD, a copresenter of the FIDELITY analysis and a lead investigator of the two finerenone trials.
When cardiologists and possibly other specialists see patients with T2D, they traditionally have focused on measuring left ventricular ejection fraction and checking for other indications of heart failure. The new results from FIDELIO-DKD and FIGARO-DKD showed that finerenone treatment can prevent heart failure onset or worsening in patients with T2D with finerenone, which clinicians can accomplish by “simply measuring UACR,” as well as eGFR, and then treating patients with abnormal levels of either, explained Dr. Agarwal, a nephrologist and professor of medicine at Indiana University in Indianapolis.
“Diabetologists know that when they see patients with diabetes they need to collect a urine sample to check for albuminuria. But when some other clinicians see a patient with type 2 diabetes and a normal eGFR, they often think that the patient is okay and don’t get a urine specimen,” noted Bertram Pitt, MD, another collaborator of the finerenone trials and a heart failure specialist affiliated with the University of Michigan in Ann Arbor.
“We need to pay more attention to UACR and albuminuria; traditionally clinicians have mostly looked at eGFR,” agreed Dipti Itchhaporia, MD, a cardiologist at the Carlton Heart and Vascular Institute of Hoag Hospital in Newport Beach, Calif. UACR “is a marker that should be shared” between endocrinologists, nephrologists, and cardiologists as they together care for patients with T2D, suggested Dr. Itchhaporia, president of the American College of Cardiology.
Two pivotal trials with consistent findings
The FIDELITY analysis combined data from the FIDELIO-DKD trial, reported in 2020, and from the FIGARO-DKD trial that was first reported during the current congress as well as in a simultaneous report published online.
Results from the two trials were very consistent, although the primary endpoint in FIDELIO-DKD was a composite measure of renal disease with the combined cardiovascular disease metric a secondary endpoint, while this got flipped in FIGARO-DKD which had the cardiovascular disease composite as its primary endpoint as the combined renal outcomes as a secondary endpoint.
In addition to showing a consistent, significant reduction in both combined cardiovascular disease events and in the specific endpoint of hospitalization for heart failure, the two trials also showed a consistent benefit for slowing renal disease progression, including significantly fewer patients developing end-stage kidney disease. In the combined FIDELITY analysis, treatment with finerenone cut the incidence of end-stage kidney disease by a significant 20% compared with placebo, and by an absolute reduction of 0.6%.
Another common finding was a relatively low incidence of hyperkalemia compared with what’s usually seen using a steroidal MRA, spironolactone or eplerenone. In the combined analysis treatment with finerenone produced a 14% incidence of any hyperkalemia compared with 7% among placebo-treated patients, and the rate of patients stopping their treatment because of hyperkalemia was 1.7% on finerenone and 0.6% on placebo.
“Finerenone is much better tolerated” than the steroidal MRAs in causing clinically significant hyperkalemia, noted Dr. Pitt. “There are a lot of misconceptions” about the potassium-raising potential of MRAs, and “people get frightened” by the potential. Spreading the message of finerenone’s relative safety “will take a lot of education,” he acknowledged. Routine monitoring of potassium levels is a key step to minimizing the risk for hyperkalemia when using finerenone, he added.
Suggested benefit from combination treatment
Another intriguing observation from FIDELITY derived from the fact that roughly 7% of enrolled patients were also on treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor at entry, and about 7% were on treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, and in both subgroups the incidence of the composite cardiovascular disease endpoint appeared to suggest additive effects of agents from either of these classes when combined with finerenone. Although the numbers of patients on combined treatment were too low to show a definitive result, “our expectation is that we will see an additive effect,” said Dr. Pitt. Ideally, patients with T2D and CKD “should be on both” an SGLT2 inhibitor and finerenone, he predicted.
SGLT2 inhibitors have now been embraced as a key treatment for patients with T2D or with heart failure with reduced ejection fraction, and the preliminary data suggest that combining these agents with finerenone can provide additional benefit, agreed Dr. Itchhaporia. Aside from the need for more evidence to prove this, there are also practical considerations of “How do we pay for all these fantastic therapies?” She expressed optimism that cost-benefit analyses will eventually show that the additive benefits justify the added cost.
Based largely on results from FIDELIO-DKD, finerenone received marketing approval from the Food and Drug Administration in July 2021 for the indication of treating patients with T2D and chronic kidney disease.
FIGARO-DKD, FIDELIO-DKD, and FIDELITY were sponsored by Bayer, the company that markets finerenone. Dr. Filippatos has received lecture fees from Bayer, and has had financial relationships with Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Agarwal received travel support from and has been a consultant to Bayer and to numerous other companies. Dr. Pitt has been a consultant to Bayer and to numerous other companies. Dr. Itchhaporia had no disclosures.
New data on using the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone to treat patients with type 2 diabetes and chronic kidney disease did more than further confirm this new drug’s efficacy in these patients for slowing progression to end-stage renal disease and reducing hospitalizations for heart failure.
It also strengthened the case for clinicians to be much more proactive in collecting urine specimens from patients with type 2 diabetes (T2D) to find those with albuminuria whose kidney function has not yet dropped below 60 mL/min per 1.73 m2, a population that the data show finerenone can help.
The FIDELITY prespecified meta-analysis combined data from two related pivotal trials of finerenone (Kerendia) in a total of more than 13,000 patients with T2D and chronic kidney disease (CKD). Each of these two trials, FIDELIO-DKD and FIGARO-DKD, identified patients with CKD by either of two methods, or a total of four different criteria.
In sum, the two trials enrolled patients with an estimated glomerular filtration rate (eGFR) of 25-90 mL/min per 1.73 m2 and a urinary albumin-to-creatinine ratio (UACR) of 30-299, or an eGFR of 25-75 mL/min per 1.73 m2 and a UACR of 300-5,000. The result was that 40% of enrolled patients had an eGFR of at least 60, levels that are considered normal, but they also had some level of albuminuria that defined them as having CKD.
The results showed that during a median follow-up of 36 months, patients with a normal eGFR and albuminuria had their combined incidence of cardiovascular disease events (cardiovascular death, MI, stroke, or hospitalization for heart failure) reduced by roughly the same amount as seen in patients with lower levels of eGFR and renal function, a finding that reimagines how clinicians need to routinely screen patients with T2D for CKD, Gerasimos Filippatos, MD, reported at the virtual annual congress of the European Society of Cardiology.
“Measuring UACR in patients with type 2 diabetes is important to identify patients who will benefit from finerenone treatment independent of their eGFR,” said Dr. Filippatos, professor of medicine at the University of Athens and director of the heart failure unit at Attikon University Hospital in Athens.
The combined FIDELITY analysis showed a significant overall cut in the combined cardiovascular disease endpoint of 14% relative to placebo, which reflected a 1.7% absolute reduction in events between the two arms during 3 years of treatment. The primary driver of this benefit was the significant drop in hospitalizations for heart failure on finerenone compared with placebo, which fell by a relative 22% and by an absolute 1.1%, Dr. Filippatos reported.
Routinely screening for albuminuria is ‘practice changing’
“This is really practice changing information for cardiologists,” said Rajiv L. Agarwal, MD, a copresenter of the FIDELITY analysis and a lead investigator of the two finerenone trials.
When cardiologists and possibly other specialists see patients with T2D, they traditionally have focused on measuring left ventricular ejection fraction and checking for other indications of heart failure. The new results from FIDELIO-DKD and FIGARO-DKD showed that finerenone treatment can prevent heart failure onset or worsening in patients with T2D with finerenone, which clinicians can accomplish by “simply measuring UACR,” as well as eGFR, and then treating patients with abnormal levels of either, explained Dr. Agarwal, a nephrologist and professor of medicine at Indiana University in Indianapolis.
“Diabetologists know that when they see patients with diabetes they need to collect a urine sample to check for albuminuria. But when some other clinicians see a patient with type 2 diabetes and a normal eGFR, they often think that the patient is okay and don’t get a urine specimen,” noted Bertram Pitt, MD, another collaborator of the finerenone trials and a heart failure specialist affiliated with the University of Michigan in Ann Arbor.
“We need to pay more attention to UACR and albuminuria; traditionally clinicians have mostly looked at eGFR,” agreed Dipti Itchhaporia, MD, a cardiologist at the Carlton Heart and Vascular Institute of Hoag Hospital in Newport Beach, Calif. UACR “is a marker that should be shared” between endocrinologists, nephrologists, and cardiologists as they together care for patients with T2D, suggested Dr. Itchhaporia, president of the American College of Cardiology.
Two pivotal trials with consistent findings
The FIDELITY analysis combined data from the FIDELIO-DKD trial, reported in 2020, and from the FIGARO-DKD trial that was first reported during the current congress as well as in a simultaneous report published online.
Results from the two trials were very consistent, although the primary endpoint in FIDELIO-DKD was a composite measure of renal disease with the combined cardiovascular disease metric a secondary endpoint, while this got flipped in FIGARO-DKD which had the cardiovascular disease composite as its primary endpoint as the combined renal outcomes as a secondary endpoint.
In addition to showing a consistent, significant reduction in both combined cardiovascular disease events and in the specific endpoint of hospitalization for heart failure, the two trials also showed a consistent benefit for slowing renal disease progression, including significantly fewer patients developing end-stage kidney disease. In the combined FIDELITY analysis, treatment with finerenone cut the incidence of end-stage kidney disease by a significant 20% compared with placebo, and by an absolute reduction of 0.6%.
Another common finding was a relatively low incidence of hyperkalemia compared with what’s usually seen using a steroidal MRA, spironolactone or eplerenone. In the combined analysis treatment with finerenone produced a 14% incidence of any hyperkalemia compared with 7% among placebo-treated patients, and the rate of patients stopping their treatment because of hyperkalemia was 1.7% on finerenone and 0.6% on placebo.
“Finerenone is much better tolerated” than the steroidal MRAs in causing clinically significant hyperkalemia, noted Dr. Pitt. “There are a lot of misconceptions” about the potassium-raising potential of MRAs, and “people get frightened” by the potential. Spreading the message of finerenone’s relative safety “will take a lot of education,” he acknowledged. Routine monitoring of potassium levels is a key step to minimizing the risk for hyperkalemia when using finerenone, he added.
Suggested benefit from combination treatment
Another intriguing observation from FIDELITY derived from the fact that roughly 7% of enrolled patients were also on treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor at entry, and about 7% were on treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, and in both subgroups the incidence of the composite cardiovascular disease endpoint appeared to suggest additive effects of agents from either of these classes when combined with finerenone. Although the numbers of patients on combined treatment were too low to show a definitive result, “our expectation is that we will see an additive effect,” said Dr. Pitt. Ideally, patients with T2D and CKD “should be on both” an SGLT2 inhibitor and finerenone, he predicted.
SGLT2 inhibitors have now been embraced as a key treatment for patients with T2D or with heart failure with reduced ejection fraction, and the preliminary data suggest that combining these agents with finerenone can provide additional benefit, agreed Dr. Itchhaporia. Aside from the need for more evidence to prove this, there are also practical considerations of “How do we pay for all these fantastic therapies?” She expressed optimism that cost-benefit analyses will eventually show that the additive benefits justify the added cost.
Based largely on results from FIDELIO-DKD, finerenone received marketing approval from the Food and Drug Administration in July 2021 for the indication of treating patients with T2D and chronic kidney disease.
FIGARO-DKD, FIDELIO-DKD, and FIDELITY were sponsored by Bayer, the company that markets finerenone. Dr. Filippatos has received lecture fees from Bayer, and has had financial relationships with Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Agarwal received travel support from and has been a consultant to Bayer and to numerous other companies. Dr. Pitt has been a consultant to Bayer and to numerous other companies. Dr. Itchhaporia had no disclosures.
FROM ESC CONGRESS 2021
Ablation at an early stage of fibrosis appears critical to improved AFib control
No benefit observed if fibrosis advanced
The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.
However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.
“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.
The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.
After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
Five percent risk reduction not significant
After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).
As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.
In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.
“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.
Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).
Subgroup data called clinically meaningful
“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”
Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.
“If the fibrosis is advanced, do PVI only,” he said.
However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.
“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”
Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
DECAAF II is not a positive trial
Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.
In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”
Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.
An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”
He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.
“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.
Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.
No benefit observed if fibrosis advanced
No benefit observed if fibrosis advanced
The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.
However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.
“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.
The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.
After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
Five percent risk reduction not significant
After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).
As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.
In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.
“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.
Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).
Subgroup data called clinically meaningful
“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”
Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.
“If the fibrosis is advanced, do PVI only,” he said.
However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.
“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”
Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
DECAAF II is not a positive trial
Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.
In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”
Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.
An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”
He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.
“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.
Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.
The addition of image-guided atrial fibrosis ablation did not significantly reduce the risk of recurrence relative to pulmonary vein isolation (PVI) alone in patients with treatment-resistant atrial fibrillation (AFib), according to results of an intention-to-treat analysis of the randomized DECAAF II trial.
However, there was a significant advantage for the addition of image-guided ablation in the subgroup of patients with stage I or II fibrosis, and this is a clinically meaningful finding, Nassir F. Marrouche, MD, reported at the annual congress of the European Society of Cardiology.
“Patients at early stages [of fibrosis] appear to do well if you do a good job covering the myopathy [with scar formation], and that is an important message,” said Dr. Marrouche, the principal investigator.
The underlying hypothesis of the DECAAF trial was that ablation guided with MRI imaging would prove superior to PVI alone in the treatment of resistant AF. There were 843 participants randomized at 44 centers. At baseline, all underwent a late gadolinium-enhancement MRI, a technique that allows detection of fibrotic tissue.
After randomization, those in the control group underwent standard of care PVI alone. Those in the intervention group underwent ablation of areas of the atrium revealed to be fibrotic on the MRI scan in addition to PVI.
Five percent risk reduction not significant
After a median follow-up of 12 months, recurrence of AFib, which was the primary endpoint, was observed in 43% in the intervention group and 46.1% in the control group. The relative 5% reduction for treatment was not statistically significant (hazard ratio, 0.95; 95% confidence interval, 0.778-1.17; P = .63).
As part of the study protocol, MRI was repeated 3 months after treatment in all patients. This permitted the investigators to evaluate the degree of scar formation in relation to the fibrosis covered in the intervention group. Independent reviewers rated this coverage on levels from 1 to 5, with 5 representing complete coverage.
In this analysis, it was found that ablation resulted in higher levels of lesion formation in those with early stages of disease, defined as stage I or II fibrosis, but lower levels in advanced stages.
“The more myopathy, the more disease, the less likelihood of lesion formation,” reported Dr. Marrouche, professor of medicine in the section of cardiology at Tulane University, New Orleans.
Attributed to the greater levels of fibrosis coverage, the risk of AF recurrence over the course of follow-up was significantly reduced in the intervention relative to the control group on as-treated analysis in patients who had stage I or II fibrosis at baseline. (HR 0.841, 95% CI, 0.732-0.968; P < .05).
Subgroup data called clinically meaningful
“This has huge implications going forward,” Dr. Marrouche maintained. In the context of a series of previous trials, including DECAAF I, which associated advanced fibrosis with higher risk of failing ablation, DECAAF II provides the groundwork for “where and how to ablate.”
Taken together, the DECAAF data suggest that there is no value in ablating advanced fibrosis. Due to the poor scar formation needed to reduce risk of AF recurrence, there are no benefits to outweigh the slightly greater risk of strokes and other adverse events observed among the intervention group in the DECAAF II trial, according to Dr. Marrouche.
“If the fibrosis is advanced, do PVI only,” he said.
However, if fibrosis remains at an early stage, defined by these data as stage II or lower, the data from DECAAF indicated that there is a benefit, according to Dr. Marrouche.
“DECAAF tells you to target early disease,” he said. Asked if he would now apply these data to treatment of patients with early fibrosis, he replied, “Yes, that’s what I am concluding.”
Several aspects of the design of DECAAF II, such as the use of a follow-up MRI to assess ablation at 3 months, were praised by Paul J. Wang, MD, director, Stanford Cardiac Arrhythmia Service, Stanford (Calif.) University, but he did not agree with Dr. Marrouche’s interpretation. This included the contention that scar formation was easier to achieve in patients with less atrial fibrosis.
DECAAF II is not a positive trial
Based on his reading of the correlation coefficients, expressed as an r value, which were 0.237 and 0.493 for the low- and high-fibrosis groups, respectively, “the difference in lesion formation in low- and high-fibrosis groups seems difficult to prove,” Dr. Wang pointed out.
In addition, “the authors suggest that the failure to achieve a good ablation lesion may account for the AFib recurrence,” said Dr. Wang, editor-in-chief of the American Heart Association’s Circulation: Arrhythmia and Electrophysiology. However, due to the many other potential variables influencing this risk, “this is difficult to show.”
Ultimately, despite a benefit observed among patients with a low level of fibrosis that was identified in an as-treated subgroup, “DECAAF II joins the numerous studies [evaluating the addition of an intervention relative to PVI alone] that have not achieved the primary endpoint,” Dr. Wang concluded.
An ESC-invited discussant, Christophe Leclercq, MD, chief of cardiology at Centre Hospitalier Universitaire, Rennes, France, made the same point. He said several previous studies have made the concept of achieving greater ablation to reduce AF recurrence “attractive,” but this “was not confirmed in DECAAF II.”
He also would not endorse MRI-guided ablation in resistant AFib among patients with early disease.
“There was a positive result observed in those with a low stage of fibrosis, but there were also more complications in those undergoing MRI-guided ablation,” he said.
Dr. Marrouche reports financial relationships with Abbott, which provided funding for this study. Dr. Wang had no disclosures. Dr. Leclercq reported financial relationships with Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical.
FROM ESC CONGRESS 2021
Biliopancreatic endoscopic drainage improves EPI in patients with unresectable pancreatic cancer
Key clinical point: Among patients with unresectable pancreatic cancer undergoing endoscopic retrograde cholangiopancreatography (ERCP), biliopancreatic, but not biliary endoscopic drainage, was associated with improvement and normalization of exocrine pancreatic function.
Major finding: At baseline, 80% of patients had exocrine pancreatic insufficiency (EPI). The median absolute improvement of 13C-cumulative recovery rate was significantly higher after biliopancreatic vs biliary drainage (23.75% vs −1.92%; P = .015). Normalization of pancreatic function was observed in all patients after biliopancreatic drainage vs only 1 patient after biliary drainage.
Study details: Findings are from a prospective analysis of 20 adult patients with obstructive jaundice secondary to unresectable pancreatic cancer who underwent ERCP and were randomly assigned to receive either biliary drainage (n=7) or biliopancreatic drainage (n=6).
Disclosures: This study was supported by the Health Research Institute of Santiago de Compostela, Spain. The authors declared no conflict of interests.
Source: Domínguez-Muñoz JE et al. Pancreas. 2021 May 20. doi: 10.1097/MPA.0000000000001817.
Key clinical point: Among patients with unresectable pancreatic cancer undergoing endoscopic retrograde cholangiopancreatography (ERCP), biliopancreatic, but not biliary endoscopic drainage, was associated with improvement and normalization of exocrine pancreatic function.
Major finding: At baseline, 80% of patients had exocrine pancreatic insufficiency (EPI). The median absolute improvement of 13C-cumulative recovery rate was significantly higher after biliopancreatic vs biliary drainage (23.75% vs −1.92%; P = .015). Normalization of pancreatic function was observed in all patients after biliopancreatic drainage vs only 1 patient after biliary drainage.
Study details: Findings are from a prospective analysis of 20 adult patients with obstructive jaundice secondary to unresectable pancreatic cancer who underwent ERCP and were randomly assigned to receive either biliary drainage (n=7) or biliopancreatic drainage (n=6).
Disclosures: This study was supported by the Health Research Institute of Santiago de Compostela, Spain. The authors declared no conflict of interests.
Source: Domínguez-Muñoz JE et al. Pancreas. 2021 May 20. doi: 10.1097/MPA.0000000000001817.
Key clinical point: Among patients with unresectable pancreatic cancer undergoing endoscopic retrograde cholangiopancreatography (ERCP), biliopancreatic, but not biliary endoscopic drainage, was associated with improvement and normalization of exocrine pancreatic function.
Major finding: At baseline, 80% of patients had exocrine pancreatic insufficiency (EPI). The median absolute improvement of 13C-cumulative recovery rate was significantly higher after biliopancreatic vs biliary drainage (23.75% vs −1.92%; P = .015). Normalization of pancreatic function was observed in all patients after biliopancreatic drainage vs only 1 patient after biliary drainage.
Study details: Findings are from a prospective analysis of 20 adult patients with obstructive jaundice secondary to unresectable pancreatic cancer who underwent ERCP and were randomly assigned to receive either biliary drainage (n=7) or biliopancreatic drainage (n=6).
Disclosures: This study was supported by the Health Research Institute of Santiago de Compostela, Spain. The authors declared no conflict of interests.
Source: Domínguez-Muñoz JE et al. Pancreas. 2021 May 20. doi: 10.1097/MPA.0000000000001817.
Point shear wave elastography may help early detection of EPI in pediatric cystic fibrosis
Key clinical point: Investigation of pancreatic elasticity and exocrine pancreatic insufficiency (EPI) using point shear wave elastography (pSWE) may provide a simple, inexpensive, and noninvasive tool for early detection of EPI, thereby influencing long-term outcomes in young patients with cystic fibrosis (CF).
Major finding: The mean pSWE was significantly lower in children with CF vs healthy children (0.97±0.16 vs 1.12±0.16; P < .001). Higher disease duration was independently associated with low pSWE (R2=0.634; P < .001).
Study details: Findings are from a prospective assessment of 55 pediatric patients with CF and 60 healthy children without any chronic diseases.
Disclosures: No source of funding was identified. The authors declared no conflict of interests.
Source: Yılmaz K et al. Pediatr Int. 2021 Aug 13. doi: 10.1111/ped.14951.
Key clinical point: Investigation of pancreatic elasticity and exocrine pancreatic insufficiency (EPI) using point shear wave elastography (pSWE) may provide a simple, inexpensive, and noninvasive tool for early detection of EPI, thereby influencing long-term outcomes in young patients with cystic fibrosis (CF).
Major finding: The mean pSWE was significantly lower in children with CF vs healthy children (0.97±0.16 vs 1.12±0.16; P < .001). Higher disease duration was independently associated with low pSWE (R2=0.634; P < .001).
Study details: Findings are from a prospective assessment of 55 pediatric patients with CF and 60 healthy children without any chronic diseases.
Disclosures: No source of funding was identified. The authors declared no conflict of interests.
Source: Yılmaz K et al. Pediatr Int. 2021 Aug 13. doi: 10.1111/ped.14951.
Key clinical point: Investigation of pancreatic elasticity and exocrine pancreatic insufficiency (EPI) using point shear wave elastography (pSWE) may provide a simple, inexpensive, and noninvasive tool for early detection of EPI, thereby influencing long-term outcomes in young patients with cystic fibrosis (CF).
Major finding: The mean pSWE was significantly lower in children with CF vs healthy children (0.97±0.16 vs 1.12±0.16; P < .001). Higher disease duration was independently associated with low pSWE (R2=0.634; P < .001).
Study details: Findings are from a prospective assessment of 55 pediatric patients with CF and 60 healthy children without any chronic diseases.
Disclosures: No source of funding was identified. The authors declared no conflict of interests.
Source: Yılmaz K et al. Pediatr Int. 2021 Aug 13. doi: 10.1111/ped.14951.
Endoscopic ultrasound finding of diffuse echogenicity of the pancreas tied to EPI
Key clinical point: The prevalence of exocrine pancreatic insufficiency (EPI) was higher in patients with diffuse echogenicity of the pancreas on endoscopic ultrasound (EUS; fatty pancreas group) vs patients with chronic diarrhea without known pancreatic disease (control group). This indicates that the EUS finding of diffuse echogenicity of the pancreas may have clinical implications on pancreatic function.
Major finding: The incidence of EPI (47% vs 6%) and chronic pancreatitis (18% vs 0%) was significantly higher (both P less than .001) in the fatty pancreas group vs control group. EPI was significantly associated with smoking (odds ratio [OR], 2.26; P = .018) and nonalcoholic fatty liver disease (OR, 4.00; P = .036) but not with chronic pancreatitis (OR, 0.70; P = .60).
Study details: Findings are from a retrospective analysis of 166 adult patients (fatty pancreas, n=89; control, n=77).
Disclosures: No source of funding was identified. MO Othman and I Raijman reported ties with various pharmaceutical companies. Other authors declared no conflict of interests.
Source: Krill JT et al. Dig Dis Sci. 2021 Aug 4. doi: 10.1007/s10620-021-07181-1
Key clinical point: The prevalence of exocrine pancreatic insufficiency (EPI) was higher in patients with diffuse echogenicity of the pancreas on endoscopic ultrasound (EUS; fatty pancreas group) vs patients with chronic diarrhea without known pancreatic disease (control group). This indicates that the EUS finding of diffuse echogenicity of the pancreas may have clinical implications on pancreatic function.
Major finding: The incidence of EPI (47% vs 6%) and chronic pancreatitis (18% vs 0%) was significantly higher (both P less than .001) in the fatty pancreas group vs control group. EPI was significantly associated with smoking (odds ratio [OR], 2.26; P = .018) and nonalcoholic fatty liver disease (OR, 4.00; P = .036) but not with chronic pancreatitis (OR, 0.70; P = .60).
Study details: Findings are from a retrospective analysis of 166 adult patients (fatty pancreas, n=89; control, n=77).
Disclosures: No source of funding was identified. MO Othman and I Raijman reported ties with various pharmaceutical companies. Other authors declared no conflict of interests.
Source: Krill JT et al. Dig Dis Sci. 2021 Aug 4. doi: 10.1007/s10620-021-07181-1
Key clinical point: The prevalence of exocrine pancreatic insufficiency (EPI) was higher in patients with diffuse echogenicity of the pancreas on endoscopic ultrasound (EUS; fatty pancreas group) vs patients with chronic diarrhea without known pancreatic disease (control group). This indicates that the EUS finding of diffuse echogenicity of the pancreas may have clinical implications on pancreatic function.
Major finding: The incidence of EPI (47% vs 6%) and chronic pancreatitis (18% vs 0%) was significantly higher (both P less than .001) in the fatty pancreas group vs control group. EPI was significantly associated with smoking (odds ratio [OR], 2.26; P = .018) and nonalcoholic fatty liver disease (OR, 4.00; P = .036) but not with chronic pancreatitis (OR, 0.70; P = .60).
Study details: Findings are from a retrospective analysis of 166 adult patients (fatty pancreas, n=89; control, n=77).
Disclosures: No source of funding was identified. MO Othman and I Raijman reported ties with various pharmaceutical companies. Other authors declared no conflict of interests.
Source: Krill JT et al. Dig Dis Sci. 2021 Aug 4. doi: 10.1007/s10620-021-07181-1
High prevalence of ‘digital’ sarcopenia in EPI
Key clinical point: Among patients undergoing endoscopic ultrasound for suspected pancreatic pathology, the presence of sarcopenia, assessed by digital skeletal muscle mass analysis, was associated with exocrine pancreatic insufficiency (EPI). Findings indicate that digital skeletal muscle analysis may aid as a nutritional assessment tool in this patient population.
Major finding: Overall, EPI was present in 45.1% of patients. The prevalence of sarcopenia (67.4% vs 37.55%; P less than .003), myosteatosis (52.2% vs 10.7%; P = .046), and sarcopenic obesity (66.7% vs 24.3%; P = .002) was significantly higher in patients with vs without EPI. Sarcopenia (odds ratio [OR], 4.8; P = .02) was strongly associated with EPI.
Study details: This prospective study included 102 patients with suspected or proven benign pancreatic pathology, chronic pancreatitis, or recurrent pancreatic type pain.
Disclosures: This study did not receive any specific funding. The authors declared no conflict of interests.
Source: Jalal M et al. Dig Dis. 2021 Jun 8. doi: 10.1159/000517554.
Key clinical point: Among patients undergoing endoscopic ultrasound for suspected pancreatic pathology, the presence of sarcopenia, assessed by digital skeletal muscle mass analysis, was associated with exocrine pancreatic insufficiency (EPI). Findings indicate that digital skeletal muscle analysis may aid as a nutritional assessment tool in this patient population.
Major finding: Overall, EPI was present in 45.1% of patients. The prevalence of sarcopenia (67.4% vs 37.55%; P less than .003), myosteatosis (52.2% vs 10.7%; P = .046), and sarcopenic obesity (66.7% vs 24.3%; P = .002) was significantly higher in patients with vs without EPI. Sarcopenia (odds ratio [OR], 4.8; P = .02) was strongly associated with EPI.
Study details: This prospective study included 102 patients with suspected or proven benign pancreatic pathology, chronic pancreatitis, or recurrent pancreatic type pain.
Disclosures: This study did not receive any specific funding. The authors declared no conflict of interests.
Source: Jalal M et al. Dig Dis. 2021 Jun 8. doi: 10.1159/000517554.
Key clinical point: Among patients undergoing endoscopic ultrasound for suspected pancreatic pathology, the presence of sarcopenia, assessed by digital skeletal muscle mass analysis, was associated with exocrine pancreatic insufficiency (EPI). Findings indicate that digital skeletal muscle analysis may aid as a nutritional assessment tool in this patient population.
Major finding: Overall, EPI was present in 45.1% of patients. The prevalence of sarcopenia (67.4% vs 37.55%; P less than .003), myosteatosis (52.2% vs 10.7%; P = .046), and sarcopenic obesity (66.7% vs 24.3%; P = .002) was significantly higher in patients with vs without EPI. Sarcopenia (odds ratio [OR], 4.8; P = .02) was strongly associated with EPI.
Study details: This prospective study included 102 patients with suspected or proven benign pancreatic pathology, chronic pancreatitis, or recurrent pancreatic type pain.
Disclosures: This study did not receive any specific funding. The authors declared no conflict of interests.
Source: Jalal M et al. Dig Dis. 2021 Jun 8. doi: 10.1159/000517554.
Treatment with GLP-1RAs improves exocrine pancreatic function in patients with T2D
Key clinical point: Treatment with both long-acting (liraglutide) and short-acting (lixisenatide) glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly improved exocrine pancreatic function in patients with type 2 diabetes (T2D).
Major finding: Fecal elastase levels increased with lixisenatide (+46.6±17.7 mg/g; P = .015) and liraglutide (+30.3±14.3 mg/g; P = .045) treatment. b-carotene levels increased with lixisenatide (+0.05±0.02 mmol/L; P = .022) but not with liraglutide (−0.00±0.02 mmol/L; P = .96) treatment. Levels of lipase and amylase increased with liraglutide (P = .0001 and P = .013, respectively) but not with lixisenatide (P = .46 and P = .93, respectively).
Study details: This study included 50 patients with T2D randomly assigned to receive a 10-week treatment of either lixisenatide (n=24) or liraglutide (n=26).
Disclosures: This study was sponsored by Novo Nordisk. Some investigators reported ties with various pharmaceutical companies including Novo Nordisk.
Source: Quast DR et al. Diabetes Obes Metab. 2021 Jun 29. doi: 10.1111/dom.14477.
Key clinical point: Treatment with both long-acting (liraglutide) and short-acting (lixisenatide) glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly improved exocrine pancreatic function in patients with type 2 diabetes (T2D).
Major finding: Fecal elastase levels increased with lixisenatide (+46.6±17.7 mg/g; P = .015) and liraglutide (+30.3±14.3 mg/g; P = .045) treatment. b-carotene levels increased with lixisenatide (+0.05±0.02 mmol/L; P = .022) but not with liraglutide (−0.00±0.02 mmol/L; P = .96) treatment. Levels of lipase and amylase increased with liraglutide (P = .0001 and P = .013, respectively) but not with lixisenatide (P = .46 and P = .93, respectively).
Study details: This study included 50 patients with T2D randomly assigned to receive a 10-week treatment of either lixisenatide (n=24) or liraglutide (n=26).
Disclosures: This study was sponsored by Novo Nordisk. Some investigators reported ties with various pharmaceutical companies including Novo Nordisk.
Source: Quast DR et al. Diabetes Obes Metab. 2021 Jun 29. doi: 10.1111/dom.14477.
Key clinical point: Treatment with both long-acting (liraglutide) and short-acting (lixisenatide) glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly improved exocrine pancreatic function in patients with type 2 diabetes (T2D).
Major finding: Fecal elastase levels increased with lixisenatide (+46.6±17.7 mg/g; P = .015) and liraglutide (+30.3±14.3 mg/g; P = .045) treatment. b-carotene levels increased with lixisenatide (+0.05±0.02 mmol/L; P = .022) but not with liraglutide (−0.00±0.02 mmol/L; P = .96) treatment. Levels of lipase and amylase increased with liraglutide (P = .0001 and P = .013, respectively) but not with lixisenatide (P = .46 and P = .93, respectively).
Study details: This study included 50 patients with T2D randomly assigned to receive a 10-week treatment of either lixisenatide (n=24) or liraglutide (n=26).
Disclosures: This study was sponsored by Novo Nordisk. Some investigators reported ties with various pharmaceutical companies including Novo Nordisk.
Source: Quast DR et al. Diabetes Obes Metab. 2021 Jun 29. doi: 10.1111/dom.14477.