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Almost half of sudden cardiac deaths linked to prior silent MI
Almost half of individuals who died of sudden cardiac death (SCD) had a myocardial scar at autopsy, indicating a prior silent myocardial infarction (SMI), in a case-controlled study.
The research team led by Juha H. Vähätalo, MD, from the University of Oulu (Finland), compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in 5,869 people in Northern Finland who had sudden cardiac deaths during 1998-2017.
Overall, 75% of the deaths were caused by coronary artery disease (CAD), and of them, 71% had no previous diagnosis of CAD. Of these latter individuals, 42% had a myocardial scar at autopsy (detected by macroscopic and microscopic evaluation of myocardium), a finding that the authors said indicated a previous, unrecognized MI.
The analysis showed that individuals with SMI were slightly older, at 69.9 years, than were those with no SMI, at 65.5 years, and were more likely to be male (83.4% vs. 75.5%).
The group with prior SMI also died during physical activity at a greater rate than did those without (18.2% vs. 12.4%), the study authors reported in their paper published in JAMA Cardiology.
The research team obtained 438 ECGs prior to SCD; 187 in individuals with SMI and 251 in the group previously diagnosed with CAD.
Of the premortem ECGs in the individuals who had had an SCD after an SMI, 67% were abnormal, the researchers reported.
The SMI group had more frequently inverted T waves (16.6% vs. 8.4%) and pathologic Q waves (12.8% vs. 6.8%), compared with the non-SMI group. Both differences were statistically significant.
Fragmented QRS was the most common marker of a scar in the SMI group, however the authors noted that the fQRS complex was “probably a sensitive marker of myocardial scarring, but its specificity is not very high”.
Overall, having at least one of the following ECG abnormalities – fQRS, Q wave, T-wave inversion, or QRS of at least 110 msec – was more common in the SMI group (66.8%) compared with the non-SMI group (55.4%).
“Among patients in whom SCD without a prior MI is the first sign of cardiac disease, a previous ECG result is likely to be normal. ... ECGs were available only in 187 individuals with SMI, so the data are not sufficient to draw definite conclusions. Rather, they support motivation for further studies on this question,” the study authors noted.
“In the future, other, more efficient methods might be useful for diagnosing SMI, in addition to standard ECGs,” such as cardiac magnetic resonance imaging, but the cost-effectiveness “is likely to be unreasonable. Therefore, screening high-risk populations with ECG to identify individuals for further examinations would probably be reasonable,” they wrote.
The research team noted some limitations of the study such as the autopsy data not revealing the size of the scar detected in the myocardium and not all individuals had an ECG recorded prior to death.
SOURCE: JAMA Cardiol. 2019 Jul 10; doi: 10.1001/jamacardio.2019.2210
Almost half of individuals who died of sudden cardiac death (SCD) had a myocardial scar at autopsy, indicating a prior silent myocardial infarction (SMI), in a case-controlled study.
The research team led by Juha H. Vähätalo, MD, from the University of Oulu (Finland), compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in 5,869 people in Northern Finland who had sudden cardiac deaths during 1998-2017.
Overall, 75% of the deaths were caused by coronary artery disease (CAD), and of them, 71% had no previous diagnosis of CAD. Of these latter individuals, 42% had a myocardial scar at autopsy (detected by macroscopic and microscopic evaluation of myocardium), a finding that the authors said indicated a previous, unrecognized MI.
The analysis showed that individuals with SMI were slightly older, at 69.9 years, than were those with no SMI, at 65.5 years, and were more likely to be male (83.4% vs. 75.5%).
The group with prior SMI also died during physical activity at a greater rate than did those without (18.2% vs. 12.4%), the study authors reported in their paper published in JAMA Cardiology.
The research team obtained 438 ECGs prior to SCD; 187 in individuals with SMI and 251 in the group previously diagnosed with CAD.
Of the premortem ECGs in the individuals who had had an SCD after an SMI, 67% were abnormal, the researchers reported.
The SMI group had more frequently inverted T waves (16.6% vs. 8.4%) and pathologic Q waves (12.8% vs. 6.8%), compared with the non-SMI group. Both differences were statistically significant.
Fragmented QRS was the most common marker of a scar in the SMI group, however the authors noted that the fQRS complex was “probably a sensitive marker of myocardial scarring, but its specificity is not very high”.
Overall, having at least one of the following ECG abnormalities – fQRS, Q wave, T-wave inversion, or QRS of at least 110 msec – was more common in the SMI group (66.8%) compared with the non-SMI group (55.4%).
“Among patients in whom SCD without a prior MI is the first sign of cardiac disease, a previous ECG result is likely to be normal. ... ECGs were available only in 187 individuals with SMI, so the data are not sufficient to draw definite conclusions. Rather, they support motivation for further studies on this question,” the study authors noted.
“In the future, other, more efficient methods might be useful for diagnosing SMI, in addition to standard ECGs,” such as cardiac magnetic resonance imaging, but the cost-effectiveness “is likely to be unreasonable. Therefore, screening high-risk populations with ECG to identify individuals for further examinations would probably be reasonable,” they wrote.
The research team noted some limitations of the study such as the autopsy data not revealing the size of the scar detected in the myocardium and not all individuals had an ECG recorded prior to death.
SOURCE: JAMA Cardiol. 2019 Jul 10; doi: 10.1001/jamacardio.2019.2210
Almost half of individuals who died of sudden cardiac death (SCD) had a myocardial scar at autopsy, indicating a prior silent myocardial infarction (SMI), in a case-controlled study.
The research team led by Juha H. Vähätalo, MD, from the University of Oulu (Finland), compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in 5,869 people in Northern Finland who had sudden cardiac deaths during 1998-2017.
Overall, 75% of the deaths were caused by coronary artery disease (CAD), and of them, 71% had no previous diagnosis of CAD. Of these latter individuals, 42% had a myocardial scar at autopsy (detected by macroscopic and microscopic evaluation of myocardium), a finding that the authors said indicated a previous, unrecognized MI.
The analysis showed that individuals with SMI were slightly older, at 69.9 years, than were those with no SMI, at 65.5 years, and were more likely to be male (83.4% vs. 75.5%).
The group with prior SMI also died during physical activity at a greater rate than did those without (18.2% vs. 12.4%), the study authors reported in their paper published in JAMA Cardiology.
The research team obtained 438 ECGs prior to SCD; 187 in individuals with SMI and 251 in the group previously diagnosed with CAD.
Of the premortem ECGs in the individuals who had had an SCD after an SMI, 67% were abnormal, the researchers reported.
The SMI group had more frequently inverted T waves (16.6% vs. 8.4%) and pathologic Q waves (12.8% vs. 6.8%), compared with the non-SMI group. Both differences were statistically significant.
Fragmented QRS was the most common marker of a scar in the SMI group, however the authors noted that the fQRS complex was “probably a sensitive marker of myocardial scarring, but its specificity is not very high”.
Overall, having at least one of the following ECG abnormalities – fQRS, Q wave, T-wave inversion, or QRS of at least 110 msec – was more common in the SMI group (66.8%) compared with the non-SMI group (55.4%).
“Among patients in whom SCD without a prior MI is the first sign of cardiac disease, a previous ECG result is likely to be normal. ... ECGs were available only in 187 individuals with SMI, so the data are not sufficient to draw definite conclusions. Rather, they support motivation for further studies on this question,” the study authors noted.
“In the future, other, more efficient methods might be useful for diagnosing SMI, in addition to standard ECGs,” such as cardiac magnetic resonance imaging, but the cost-effectiveness “is likely to be unreasonable. Therefore, screening high-risk populations with ECG to identify individuals for further examinations would probably be reasonable,” they wrote.
The research team noted some limitations of the study such as the autopsy data not revealing the size of the scar detected in the myocardium and not all individuals had an ECG recorded prior to death.
SOURCE: JAMA Cardiol. 2019 Jul 10; doi: 10.1001/jamacardio.2019.2210
FROM JAMA CARDIOLOGY
Risk of atrial fibrillation 900% higher with cancer
MELBOURNE – The overall prevalence of atrial fibrillation in people who have or have had cancer is 10 times that of individuals without cancer, according to a study presented at the International Society on Thrombosis and Haemostasis congress.
Cihan Ay, MD, of the division of hematology and hemostaseology at the Medical University of Vienna reported on a nationwide cohort study using health insurance data from more than 8.3 million people in Austria, including roughly 159,000 with a diagnosis of cancer and 113,000 with a diagnosis of atrial fibrillation.
The analysis found that, in individuals whose records showed a diagnosis of cancer, there was a 950% higher relative risk of also having a diagnosis of atrial fibrillation, compared with those with no cancer diagnosis.
The overall prevalence of atrial fibrillation among individuals with a cancer diagnosis was 9.8%, compared with 1.2% in those without cancer.
There was significant variation in relative risk according to age. Although the prevalence of atrial fibrillation increased with age, the highest relative risks were seen in the youngest age groups.
In those aged 12 years or under with a cancer diagnosis, the relative risk of atrial fibrillation was 150 times greater than in those without cancer, and in those aged 13-18 years, it was 200 times higher. At the other end of the age spectrum, individuals aged 70-79 years with a recorded cancer diagnosis, the relative risk of atrial fibrillation was still 130% higher than the noncancer population, and in those aged 80-90 years it was a significant 54% higher.
However, the analysis did not find any effect of gender on the risk of atrial fibrillation associated with cancer, regardless of the age group.
Researchers also examined the influence of different cancer types. They found the highest relative risk of atrial fibrillation was in persons with hematologic malignancies – at nine times the risk in the noncancer population – and the lowest was in the endocrine cancer patients, who had three times the risk.
Dr. Ay told the conference that the association between cancer and atrial fibrillation had been suggested in the literature, but it was still an unexplored field. “The exact magnitude of this association between cancer and atrial fibrillation is still unclear.”
There was also the question of what mechanisms might underlie the association. Dr. Ay pointed out that the health insurance database did not allow researchers to explore the temporal relationship between the two diagnoses, and therefore could not tell which came first.
One audience member queried whether the fact that cancer patients were likely to be visiting a clinician more frequently might mean that the atrial fibrillation would be more likely to be diagnosed.
To that, Dr. Ay suggested the significantly higher relative risk in children was supportive of the notion that cancer itself, or treatment effects, were influencing atrial fibrillation risk.
“There is evidence suggesting that cancer treatments are triggering atrial fibrillation,” he said in an interview. “Also, patients with cancer have situations of in which they are sick – they have neutropenia or sepsis and so on – which can also trigger atrial fibrillation.”
Given the limitations of the retrospective cohort study, Dr. Ay said he was hoping to do a prospective study that would enable baseline measurements of cancer patients to determine how much of the atrial fibrillation was preexisting.
“We have also more and more cancer survivors, and over the years they’re living longer and the likelihood of getting atrial fibrillation increases,” he added.
Commenting on the data, Gerald Soff, MD, chief of hematology at the Memorial Sloan Kettering Cancer Center in New York, said it was very important to quantify the association between cancer and atrial fibrillation.
“What’s striking to me is how many people with cancer come in with preexisting atrial fibrillation,” he said. “It could be that they have cancer and they’re already messed up, but we have, on a given day, several people coming in with newly diagnosed cancers, already on warfarin or apixaban or rivaroxaban because they have atrial fibrillation.”
Dr. Ay reported advisory board positions and speaking engagements for the pharmaceutical sector.
MELBOURNE – The overall prevalence of atrial fibrillation in people who have or have had cancer is 10 times that of individuals without cancer, according to a study presented at the International Society on Thrombosis and Haemostasis congress.
Cihan Ay, MD, of the division of hematology and hemostaseology at the Medical University of Vienna reported on a nationwide cohort study using health insurance data from more than 8.3 million people in Austria, including roughly 159,000 with a diagnosis of cancer and 113,000 with a diagnosis of atrial fibrillation.
The analysis found that, in individuals whose records showed a diagnosis of cancer, there was a 950% higher relative risk of also having a diagnosis of atrial fibrillation, compared with those with no cancer diagnosis.
The overall prevalence of atrial fibrillation among individuals with a cancer diagnosis was 9.8%, compared with 1.2% in those without cancer.
There was significant variation in relative risk according to age. Although the prevalence of atrial fibrillation increased with age, the highest relative risks were seen in the youngest age groups.
In those aged 12 years or under with a cancer diagnosis, the relative risk of atrial fibrillation was 150 times greater than in those without cancer, and in those aged 13-18 years, it was 200 times higher. At the other end of the age spectrum, individuals aged 70-79 years with a recorded cancer diagnosis, the relative risk of atrial fibrillation was still 130% higher than the noncancer population, and in those aged 80-90 years it was a significant 54% higher.
However, the analysis did not find any effect of gender on the risk of atrial fibrillation associated with cancer, regardless of the age group.
Researchers also examined the influence of different cancer types. They found the highest relative risk of atrial fibrillation was in persons with hematologic malignancies – at nine times the risk in the noncancer population – and the lowest was in the endocrine cancer patients, who had three times the risk.
Dr. Ay told the conference that the association between cancer and atrial fibrillation had been suggested in the literature, but it was still an unexplored field. “The exact magnitude of this association between cancer and atrial fibrillation is still unclear.”
There was also the question of what mechanisms might underlie the association. Dr. Ay pointed out that the health insurance database did not allow researchers to explore the temporal relationship between the two diagnoses, and therefore could not tell which came first.
One audience member queried whether the fact that cancer patients were likely to be visiting a clinician more frequently might mean that the atrial fibrillation would be more likely to be diagnosed.
To that, Dr. Ay suggested the significantly higher relative risk in children was supportive of the notion that cancer itself, or treatment effects, were influencing atrial fibrillation risk.
“There is evidence suggesting that cancer treatments are triggering atrial fibrillation,” he said in an interview. “Also, patients with cancer have situations of in which they are sick – they have neutropenia or sepsis and so on – which can also trigger atrial fibrillation.”
Given the limitations of the retrospective cohort study, Dr. Ay said he was hoping to do a prospective study that would enable baseline measurements of cancer patients to determine how much of the atrial fibrillation was preexisting.
“We have also more and more cancer survivors, and over the years they’re living longer and the likelihood of getting atrial fibrillation increases,” he added.
Commenting on the data, Gerald Soff, MD, chief of hematology at the Memorial Sloan Kettering Cancer Center in New York, said it was very important to quantify the association between cancer and atrial fibrillation.
“What’s striking to me is how many people with cancer come in with preexisting atrial fibrillation,” he said. “It could be that they have cancer and they’re already messed up, but we have, on a given day, several people coming in with newly diagnosed cancers, already on warfarin or apixaban or rivaroxaban because they have atrial fibrillation.”
Dr. Ay reported advisory board positions and speaking engagements for the pharmaceutical sector.
MELBOURNE – The overall prevalence of atrial fibrillation in people who have or have had cancer is 10 times that of individuals without cancer, according to a study presented at the International Society on Thrombosis and Haemostasis congress.
Cihan Ay, MD, of the division of hematology and hemostaseology at the Medical University of Vienna reported on a nationwide cohort study using health insurance data from more than 8.3 million people in Austria, including roughly 159,000 with a diagnosis of cancer and 113,000 with a diagnosis of atrial fibrillation.
The analysis found that, in individuals whose records showed a diagnosis of cancer, there was a 950% higher relative risk of also having a diagnosis of atrial fibrillation, compared with those with no cancer diagnosis.
The overall prevalence of atrial fibrillation among individuals with a cancer diagnosis was 9.8%, compared with 1.2% in those without cancer.
There was significant variation in relative risk according to age. Although the prevalence of atrial fibrillation increased with age, the highest relative risks were seen in the youngest age groups.
In those aged 12 years or under with a cancer diagnosis, the relative risk of atrial fibrillation was 150 times greater than in those without cancer, and in those aged 13-18 years, it was 200 times higher. At the other end of the age spectrum, individuals aged 70-79 years with a recorded cancer diagnosis, the relative risk of atrial fibrillation was still 130% higher than the noncancer population, and in those aged 80-90 years it was a significant 54% higher.
However, the analysis did not find any effect of gender on the risk of atrial fibrillation associated with cancer, regardless of the age group.
Researchers also examined the influence of different cancer types. They found the highest relative risk of atrial fibrillation was in persons with hematologic malignancies – at nine times the risk in the noncancer population – and the lowest was in the endocrine cancer patients, who had three times the risk.
Dr. Ay told the conference that the association between cancer and atrial fibrillation had been suggested in the literature, but it was still an unexplored field. “The exact magnitude of this association between cancer and atrial fibrillation is still unclear.”
There was also the question of what mechanisms might underlie the association. Dr. Ay pointed out that the health insurance database did not allow researchers to explore the temporal relationship between the two diagnoses, and therefore could not tell which came first.
One audience member queried whether the fact that cancer patients were likely to be visiting a clinician more frequently might mean that the atrial fibrillation would be more likely to be diagnosed.
To that, Dr. Ay suggested the significantly higher relative risk in children was supportive of the notion that cancer itself, or treatment effects, were influencing atrial fibrillation risk.
“There is evidence suggesting that cancer treatments are triggering atrial fibrillation,” he said in an interview. “Also, patients with cancer have situations of in which they are sick – they have neutropenia or sepsis and so on – which can also trigger atrial fibrillation.”
Given the limitations of the retrospective cohort study, Dr. Ay said he was hoping to do a prospective study that would enable baseline measurements of cancer patients to determine how much of the atrial fibrillation was preexisting.
“We have also more and more cancer survivors, and over the years they’re living longer and the likelihood of getting atrial fibrillation increases,” he added.
Commenting on the data, Gerald Soff, MD, chief of hematology at the Memorial Sloan Kettering Cancer Center in New York, said it was very important to quantify the association between cancer and atrial fibrillation.
“What’s striking to me is how many people with cancer come in with preexisting atrial fibrillation,” he said. “It could be that they have cancer and they’re already messed up, but we have, on a given day, several people coming in with newly diagnosed cancers, already on warfarin or apixaban or rivaroxaban because they have atrial fibrillation.”
Dr. Ay reported advisory board positions and speaking engagements for the pharmaceutical sector.
REPORTING FROM 2019 ISTH CONGRESS
Pivotal trial shows HFrEF benefits from baroreceptor stimulation
SAN FRANCISCO – Baroreflex activation therapy met all four of its primary endpoints in its U.S. pivotal trial of 264 patients with advanced heart failure with reduced ejection fraction who were ineligible for cardiac resynchronization therapy.
The results showed that ongoing baroreflex activation therapy (BAT) via a single, stimulating electrode surgically placed on a patient’s carotid artery led to statistically significant and clinically meaningful improvements in quality of life and functional capacity while also reducing the level of a biomarker of heart failure severity in patients already on guideline-directed medical therapy, Michael R. Zile, MD, said at the annual scientific sessions of the Heart Rhythm Society. He estimated that the device is appropriate for perhaps a third or more of patients with heart failure with reduced ejection fraction (HFrEF), specifically patients with New York Heart Association functional class III disease who are not candidates for treatment with cardiac resynchronization therapy (CRT) and with a blood level of N-terminal pro–brain natriuretic peptide (NT-proBNP) of less than 1,600 pg/mL, a cutoff that excludes patients with very severe class III HFrEF and focuses on those who benefited in the study.
“To our knowledge, this is the first successful pivotal trial of device-based neuromodulation therapy in HFrEF patients,” said Dr. Zile, professor of medicine at the Medical University of South Carolina in Charleston. “We think that BAT fills an unmet need” in a large number of HFrEF patients. He stressed that the placement of the single, 2-mm, unilateral electrode on the baroreceptor-containing carotid sinus is an “extremely safe and simple” surgery. The electrode attaches to a small, subcutaneously placed generator.
Dr. Zile attributed the treatment’s success, in contrast to a prior, failed attempt to treat HFrEF by vagus nerve stimulation (J Am Coll Cardiol. 2016 Jul 12;68[2]:147-56) to BAT’s action via the patient’s brain, which processes the afferent signal it receives from stimulation to in turn inhibit sympathetic activation and upregulate parasympathetic innervation, with both actions benefiting HFrEF patients. “The integrated autonomic balance is the real difference with this device,” he said. Other helpful effects from BAT are reduced heart rate, reduced cardiac remodeling, increased vasodilation, a decrease in elevated blood pressure, increased diuresis, and a drop in renin secretion. The pivotal trial built on findings from a phase 2 study (JACC Heart Fail. 2015 Jun;3[6]:487-96).
The BeAT-HF (Barostim Neo - Baroreflex Activation Therapy for Heart Failure) trial enrolled patients with class III HFrEF with a left ventricular ejection fraction of 35% or less and a 6-minute walk distance of 150-400 m, who were ineligible for CRT, on optimal medical therapy, and who had an elevated NT-proBNP level. After the study randomized 271 patients to either BAT or ongoing medical therapy only (without use of a sham procedure or sham BAT), the results showed a statistically significant benefit for three of the four primary endpoints. Patients treated with BAT for 6 months had statistically significant and clinically meaningful improvements in their quality of life scores as measured on the Minnesota Living With Heart Failure Questionnaire, in their function as measured by the 6-min walk distance, and in the treatment’s safety, based on the combined rate of major adverse neurological and cardiovascular events, which occurred in 6% of patients treated with BAT, which was significantly better than the study’s prespecified performance goal of 15%.
However, for the fourth primary endpoint – reduction in blood levels of NT-proBNP – the BAT-treated patients showed no significant improvement, compared with the controls. The design of BeAT-HF called for consultation with the Food and Drug Administration in such a situation, and further data analysis showed that the problem may have been that some enrolled patients entered with extremely elevated levels of this biomarker. The agency authorized an added protocol that randomized 102 additional patients that matched the initial cohort but had a requirement for an NT-proBNP level of less than 1,600 pg/mL. The 6-month outcomes of these patients were combined with the previously determined outcomes for 162 of the original 271 patients who entered with NT-proBNP levels within the specified limit, producing a total, final study group of 264 patients, of whom 120 received BAT and completed 6-month follow-up, and 125 received medical therapy only and had 6-month follow-up. These patients averaged about 63 years of age, and 20% were women. On average they were on four heart failure medications, and more than three-quarters also had an implanted cardiac device.
The results from an analysis of this cohort showed a statistically significant, 25% relative reduction in blood levels of NT-proBNP in the BAT patients, compared with the controls, and it also confirmed statistically significant and meaningful improvements in quality of life and function on BAT, compared with controls. The 14-point average improvement in the quality of life score in BAT patients, compared with the controls, on the Minnesota Living With Heart Failure Questionnaire was nearly triple the point improvement that’s considered clinically meaningful and hence was “very convincing” about the treatment’s efficacy, noted Dr. Zile, who is also director of cardiology at the VA Medical Center in Charleston. The 25% drop in average NT-proBNP levels “predicts a marked reduction in morbidity and mortality.” He added that researchers have developed a percutaneous, transcatheter method for placing the carotid electrode that will soon undergo clinical testing.
These results “reconfirm the safety of BAT,” but are limited by a relatively short follow-up of 6 months, no data on survival benefit, and by not having echocardiographic data on possible cardiac remodeling, commented Sanjeev Saksena, MD, medical director of the Electrophysiology Research Foundation in Warren, N.J.
BeAT-HF was sponsored by CVRx, the company developing the baroreflex activation device. Dr. Zile has been a consultant to CVRx and to Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, and Novartis. Dr. Saksena had no disclosures.
SOURCE: Zile MR. Heart Rhythm 2019, Abstract, S-LBCT01-04.
The results that Dr. Zile reported are obviously very promising. It was a huge step forward when researchers identified medical treatments that can safely manipulate the autonomic nervous system in patients with heart failure with reduced ejection fraction. Now we are asking what else we can do because we have run into limits on what we can accomplish with drugs alone. The BeAT-HF study is a step in that direction.
Andrew D. Krahn, MD, is professor of medicine and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. He has been a consultant to Medtronic and he has received research funding from Boston Scientific and Medtronic. He made these comments as a discussant for BeAT-HF.
The results that Dr. Zile reported are obviously very promising. It was a huge step forward when researchers identified medical treatments that can safely manipulate the autonomic nervous system in patients with heart failure with reduced ejection fraction. Now we are asking what else we can do because we have run into limits on what we can accomplish with drugs alone. The BeAT-HF study is a step in that direction.
Andrew D. Krahn, MD, is professor of medicine and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. He has been a consultant to Medtronic and he has received research funding from Boston Scientific and Medtronic. He made these comments as a discussant for BeAT-HF.
The results that Dr. Zile reported are obviously very promising. It was a huge step forward when researchers identified medical treatments that can safely manipulate the autonomic nervous system in patients with heart failure with reduced ejection fraction. Now we are asking what else we can do because we have run into limits on what we can accomplish with drugs alone. The BeAT-HF study is a step in that direction.
Andrew D. Krahn, MD, is professor of medicine and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. He has been a consultant to Medtronic and he has received research funding from Boston Scientific and Medtronic. He made these comments as a discussant for BeAT-HF.
SAN FRANCISCO – Baroreflex activation therapy met all four of its primary endpoints in its U.S. pivotal trial of 264 patients with advanced heart failure with reduced ejection fraction who were ineligible for cardiac resynchronization therapy.
The results showed that ongoing baroreflex activation therapy (BAT) via a single, stimulating electrode surgically placed on a patient’s carotid artery led to statistically significant and clinically meaningful improvements in quality of life and functional capacity while also reducing the level of a biomarker of heart failure severity in patients already on guideline-directed medical therapy, Michael R. Zile, MD, said at the annual scientific sessions of the Heart Rhythm Society. He estimated that the device is appropriate for perhaps a third or more of patients with heart failure with reduced ejection fraction (HFrEF), specifically patients with New York Heart Association functional class III disease who are not candidates for treatment with cardiac resynchronization therapy (CRT) and with a blood level of N-terminal pro–brain natriuretic peptide (NT-proBNP) of less than 1,600 pg/mL, a cutoff that excludes patients with very severe class III HFrEF and focuses on those who benefited in the study.
“To our knowledge, this is the first successful pivotal trial of device-based neuromodulation therapy in HFrEF patients,” said Dr. Zile, professor of medicine at the Medical University of South Carolina in Charleston. “We think that BAT fills an unmet need” in a large number of HFrEF patients. He stressed that the placement of the single, 2-mm, unilateral electrode on the baroreceptor-containing carotid sinus is an “extremely safe and simple” surgery. The electrode attaches to a small, subcutaneously placed generator.
Dr. Zile attributed the treatment’s success, in contrast to a prior, failed attempt to treat HFrEF by vagus nerve stimulation (J Am Coll Cardiol. 2016 Jul 12;68[2]:147-56) to BAT’s action via the patient’s brain, which processes the afferent signal it receives from stimulation to in turn inhibit sympathetic activation and upregulate parasympathetic innervation, with both actions benefiting HFrEF patients. “The integrated autonomic balance is the real difference with this device,” he said. Other helpful effects from BAT are reduced heart rate, reduced cardiac remodeling, increased vasodilation, a decrease in elevated blood pressure, increased diuresis, and a drop in renin secretion. The pivotal trial built on findings from a phase 2 study (JACC Heart Fail. 2015 Jun;3[6]:487-96).
The BeAT-HF (Barostim Neo - Baroreflex Activation Therapy for Heart Failure) trial enrolled patients with class III HFrEF with a left ventricular ejection fraction of 35% or less and a 6-minute walk distance of 150-400 m, who were ineligible for CRT, on optimal medical therapy, and who had an elevated NT-proBNP level. After the study randomized 271 patients to either BAT or ongoing medical therapy only (without use of a sham procedure or sham BAT), the results showed a statistically significant benefit for three of the four primary endpoints. Patients treated with BAT for 6 months had statistically significant and clinically meaningful improvements in their quality of life scores as measured on the Minnesota Living With Heart Failure Questionnaire, in their function as measured by the 6-min walk distance, and in the treatment’s safety, based on the combined rate of major adverse neurological and cardiovascular events, which occurred in 6% of patients treated with BAT, which was significantly better than the study’s prespecified performance goal of 15%.
However, for the fourth primary endpoint – reduction in blood levels of NT-proBNP – the BAT-treated patients showed no significant improvement, compared with the controls. The design of BeAT-HF called for consultation with the Food and Drug Administration in such a situation, and further data analysis showed that the problem may have been that some enrolled patients entered with extremely elevated levels of this biomarker. The agency authorized an added protocol that randomized 102 additional patients that matched the initial cohort but had a requirement for an NT-proBNP level of less than 1,600 pg/mL. The 6-month outcomes of these patients were combined with the previously determined outcomes for 162 of the original 271 patients who entered with NT-proBNP levels within the specified limit, producing a total, final study group of 264 patients, of whom 120 received BAT and completed 6-month follow-up, and 125 received medical therapy only and had 6-month follow-up. These patients averaged about 63 years of age, and 20% were women. On average they were on four heart failure medications, and more than three-quarters also had an implanted cardiac device.
The results from an analysis of this cohort showed a statistically significant, 25% relative reduction in blood levels of NT-proBNP in the BAT patients, compared with the controls, and it also confirmed statistically significant and meaningful improvements in quality of life and function on BAT, compared with controls. The 14-point average improvement in the quality of life score in BAT patients, compared with the controls, on the Minnesota Living With Heart Failure Questionnaire was nearly triple the point improvement that’s considered clinically meaningful and hence was “very convincing” about the treatment’s efficacy, noted Dr. Zile, who is also director of cardiology at the VA Medical Center in Charleston. The 25% drop in average NT-proBNP levels “predicts a marked reduction in morbidity and mortality.” He added that researchers have developed a percutaneous, transcatheter method for placing the carotid electrode that will soon undergo clinical testing.
These results “reconfirm the safety of BAT,” but are limited by a relatively short follow-up of 6 months, no data on survival benefit, and by not having echocardiographic data on possible cardiac remodeling, commented Sanjeev Saksena, MD, medical director of the Electrophysiology Research Foundation in Warren, N.J.
BeAT-HF was sponsored by CVRx, the company developing the baroreflex activation device. Dr. Zile has been a consultant to CVRx and to Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, and Novartis. Dr. Saksena had no disclosures.
SOURCE: Zile MR. Heart Rhythm 2019, Abstract, S-LBCT01-04.
SAN FRANCISCO – Baroreflex activation therapy met all four of its primary endpoints in its U.S. pivotal trial of 264 patients with advanced heart failure with reduced ejection fraction who were ineligible for cardiac resynchronization therapy.
The results showed that ongoing baroreflex activation therapy (BAT) via a single, stimulating electrode surgically placed on a patient’s carotid artery led to statistically significant and clinically meaningful improvements in quality of life and functional capacity while also reducing the level of a biomarker of heart failure severity in patients already on guideline-directed medical therapy, Michael R. Zile, MD, said at the annual scientific sessions of the Heart Rhythm Society. He estimated that the device is appropriate for perhaps a third or more of patients with heart failure with reduced ejection fraction (HFrEF), specifically patients with New York Heart Association functional class III disease who are not candidates for treatment with cardiac resynchronization therapy (CRT) and with a blood level of N-terminal pro–brain natriuretic peptide (NT-proBNP) of less than 1,600 pg/mL, a cutoff that excludes patients with very severe class III HFrEF and focuses on those who benefited in the study.
“To our knowledge, this is the first successful pivotal trial of device-based neuromodulation therapy in HFrEF patients,” said Dr. Zile, professor of medicine at the Medical University of South Carolina in Charleston. “We think that BAT fills an unmet need” in a large number of HFrEF patients. He stressed that the placement of the single, 2-mm, unilateral electrode on the baroreceptor-containing carotid sinus is an “extremely safe and simple” surgery. The electrode attaches to a small, subcutaneously placed generator.
Dr. Zile attributed the treatment’s success, in contrast to a prior, failed attempt to treat HFrEF by vagus nerve stimulation (J Am Coll Cardiol. 2016 Jul 12;68[2]:147-56) to BAT’s action via the patient’s brain, which processes the afferent signal it receives from stimulation to in turn inhibit sympathetic activation and upregulate parasympathetic innervation, with both actions benefiting HFrEF patients. “The integrated autonomic balance is the real difference with this device,” he said. Other helpful effects from BAT are reduced heart rate, reduced cardiac remodeling, increased vasodilation, a decrease in elevated blood pressure, increased diuresis, and a drop in renin secretion. The pivotal trial built on findings from a phase 2 study (JACC Heart Fail. 2015 Jun;3[6]:487-96).
The BeAT-HF (Barostim Neo - Baroreflex Activation Therapy for Heart Failure) trial enrolled patients with class III HFrEF with a left ventricular ejection fraction of 35% or less and a 6-minute walk distance of 150-400 m, who were ineligible for CRT, on optimal medical therapy, and who had an elevated NT-proBNP level. After the study randomized 271 patients to either BAT or ongoing medical therapy only (without use of a sham procedure or sham BAT), the results showed a statistically significant benefit for three of the four primary endpoints. Patients treated with BAT for 6 months had statistically significant and clinically meaningful improvements in their quality of life scores as measured on the Minnesota Living With Heart Failure Questionnaire, in their function as measured by the 6-min walk distance, and in the treatment’s safety, based on the combined rate of major adverse neurological and cardiovascular events, which occurred in 6% of patients treated with BAT, which was significantly better than the study’s prespecified performance goal of 15%.
However, for the fourth primary endpoint – reduction in blood levels of NT-proBNP – the BAT-treated patients showed no significant improvement, compared with the controls. The design of BeAT-HF called for consultation with the Food and Drug Administration in such a situation, and further data analysis showed that the problem may have been that some enrolled patients entered with extremely elevated levels of this biomarker. The agency authorized an added protocol that randomized 102 additional patients that matched the initial cohort but had a requirement for an NT-proBNP level of less than 1,600 pg/mL. The 6-month outcomes of these patients were combined with the previously determined outcomes for 162 of the original 271 patients who entered with NT-proBNP levels within the specified limit, producing a total, final study group of 264 patients, of whom 120 received BAT and completed 6-month follow-up, and 125 received medical therapy only and had 6-month follow-up. These patients averaged about 63 years of age, and 20% were women. On average they were on four heart failure medications, and more than three-quarters also had an implanted cardiac device.
The results from an analysis of this cohort showed a statistically significant, 25% relative reduction in blood levels of NT-proBNP in the BAT patients, compared with the controls, and it also confirmed statistically significant and meaningful improvements in quality of life and function on BAT, compared with controls. The 14-point average improvement in the quality of life score in BAT patients, compared with the controls, on the Minnesota Living With Heart Failure Questionnaire was nearly triple the point improvement that’s considered clinically meaningful and hence was “very convincing” about the treatment’s efficacy, noted Dr. Zile, who is also director of cardiology at the VA Medical Center in Charleston. The 25% drop in average NT-proBNP levels “predicts a marked reduction in morbidity and mortality.” He added that researchers have developed a percutaneous, transcatheter method for placing the carotid electrode that will soon undergo clinical testing.
These results “reconfirm the safety of BAT,” but are limited by a relatively short follow-up of 6 months, no data on survival benefit, and by not having echocardiographic data on possible cardiac remodeling, commented Sanjeev Saksena, MD, medical director of the Electrophysiology Research Foundation in Warren, N.J.
BeAT-HF was sponsored by CVRx, the company developing the baroreflex activation device. Dr. Zile has been a consultant to CVRx and to Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, and Novartis. Dr. Saksena had no disclosures.
SOURCE: Zile MR. Heart Rhythm 2019, Abstract, S-LBCT01-04.
REPORTING FROM HEART RHYTHM 2019
DOACs surpass warfarin in low-weight AFib patients
SAN FRANCISCO – The direct-acting anticoagulants, as a class, were more effective and at least as safe as warfarin in low-weight and very-low-weight patients with atrial fibrillation in an adjusted analysis of real-world outcomes data from more than 21,000 Korean patients.
The analysis also showed that the direct-acting oral anticoagulants (DOACs) had the best safety and efficacy on low-weight patients when used at the labeled dosages, with blunted efficacy and safety at dosages that either exceeded or fell short of labeled levels, So-Ryoung Lee, MD, said at the annual scientific sessions of the Heart Rhythm Society.
The overall superiority of DOACs by both efficacy and safety also generally extended to the subgroup of very-low-weight patients, those with weights of less than 50 kg. In this subgroup, which was 28% of the total population studied, the composite adverse event outcome occurred 33% less often among patients treated with a DOAC relative to patients treated with warfarin, a statistically significant difference, said Dr. Lee, a cardiologist at Seoul (South Korea) National University Hospital. Among all patients with weights of 60 kg (132 pounds) or less, the composite outcome occurred 34% less often in the DOAC-treated patients relative to the warfarin-treated patients, also a statistically significant difference.
Dr. Lee and colleagues used a Korean National Health Insurance database that included information on more than 600,000 adults with atrial fibrillation (AFib) as of January 2013. The researchers whittled this down to 21,678 patients who began for the first time treatment with an oral anticoagulant starting during or after January 2014; had no history of a stroke, intracranial hemorrhage, or gastrointestinal bleed; and weighed no more than 60 kg. This cohort included 7,575 (35%) who received warfarin treatment, and 14,103 (65%) who received a DOAC. Within the DOAC-treated group, 42% received rivaroxaban (Xarelto), 26% dabigatran (Pradaxa), 24% apixaban (Eliquis), and 8% edoxaban (Savaysa).
To account for baseline differences in demographics and comorbidities between the patients treated with a DOAC and those who received warfarin, Dr. Lee and her associates did propensity score adjustment, which resulted in similar cohorts of 6,692 patients treated with warfarin and 12,810 patients treated with a DOAC. The average age of these patients was 73 years, a third were men, and the average body mass index was just over 22 kg/m2.
The events that the researchers tallied during follow-up through December 2016 included rates of all-cause death, ischemic stroke, intracranial hemorrhage, hospitalization for GI bleeding, hospitalization for major bleeding, and the composite of these five outcomes.
In the propensity-score adjusted full cohort of all patients who weighed 60 kg or less, the rate of each of these five outcomes, as well as the composite outcome, occurred statistically significantly less often among the DOAC-treated patients than in those on warfarin. The reductions ranged from a 41% lower incidence of ischemic stroke on DOAC treatment compared with warfarin treatment, to an 18% reduced rate of hospitalization for a GI bleed, compared with warfarin-treated patients. In the subgroup of patients who weighed less than 50 kg (110 pounds), the reductions ranged from a 41% cut in ischemic stroke on a DOAC compared with warfarin to a 24% relative reduction in the rate of hospitalization for a major bleed, a difference that just reached statistical significance. The outcome of hospitalization for a GI bleed showed no significant between-group difference among very-low-weight patients, but the rates of intracranial hemorrhage and all-cause death also showed statistically significant lower rates among DOAC-treated patients.
Nearly two-thirds of the patients on a DOAC received the label-appropriate dose of the drug, but 31% received a dosage that was below the labeled level while 4% received a dosage above the labeled level. An analysis that divided the NOAC patients by the appropriateness of their treatment dosages showed that patients on the correct dosages fared best. For example, in the total cohort of patients who weighed 60 kg or less, those on the correct DOAC dosage had a 9.1% rate of the combined endpoint. Patients on a low DOAC dosage did about as well as did the patients on warfarin, with a combined event rate of 11.6% in each of these subgroups. The worst outcomes occurred among the small number of patients on an inappropriately-high DOAC dosage, with a combined event rate of 15.4%. The researchers found a similar pattern among patients who weighed less than 50 kg.
Dr. Lee had no disclosures.
SOURCE: Lee SR et al. HRS 2019, Abstract S-AB30-05.
SAN FRANCISCO – The direct-acting anticoagulants, as a class, were more effective and at least as safe as warfarin in low-weight and very-low-weight patients with atrial fibrillation in an adjusted analysis of real-world outcomes data from more than 21,000 Korean patients.
The analysis also showed that the direct-acting oral anticoagulants (DOACs) had the best safety and efficacy on low-weight patients when used at the labeled dosages, with blunted efficacy and safety at dosages that either exceeded or fell short of labeled levels, So-Ryoung Lee, MD, said at the annual scientific sessions of the Heart Rhythm Society.
The overall superiority of DOACs by both efficacy and safety also generally extended to the subgroup of very-low-weight patients, those with weights of less than 50 kg. In this subgroup, which was 28% of the total population studied, the composite adverse event outcome occurred 33% less often among patients treated with a DOAC relative to patients treated with warfarin, a statistically significant difference, said Dr. Lee, a cardiologist at Seoul (South Korea) National University Hospital. Among all patients with weights of 60 kg (132 pounds) or less, the composite outcome occurred 34% less often in the DOAC-treated patients relative to the warfarin-treated patients, also a statistically significant difference.
Dr. Lee and colleagues used a Korean National Health Insurance database that included information on more than 600,000 adults with atrial fibrillation (AFib) as of January 2013. The researchers whittled this down to 21,678 patients who began for the first time treatment with an oral anticoagulant starting during or after January 2014; had no history of a stroke, intracranial hemorrhage, or gastrointestinal bleed; and weighed no more than 60 kg. This cohort included 7,575 (35%) who received warfarin treatment, and 14,103 (65%) who received a DOAC. Within the DOAC-treated group, 42% received rivaroxaban (Xarelto), 26% dabigatran (Pradaxa), 24% apixaban (Eliquis), and 8% edoxaban (Savaysa).
To account for baseline differences in demographics and comorbidities between the patients treated with a DOAC and those who received warfarin, Dr. Lee and her associates did propensity score adjustment, which resulted in similar cohorts of 6,692 patients treated with warfarin and 12,810 patients treated with a DOAC. The average age of these patients was 73 years, a third were men, and the average body mass index was just over 22 kg/m2.
The events that the researchers tallied during follow-up through December 2016 included rates of all-cause death, ischemic stroke, intracranial hemorrhage, hospitalization for GI bleeding, hospitalization for major bleeding, and the composite of these five outcomes.
In the propensity-score adjusted full cohort of all patients who weighed 60 kg or less, the rate of each of these five outcomes, as well as the composite outcome, occurred statistically significantly less often among the DOAC-treated patients than in those on warfarin. The reductions ranged from a 41% lower incidence of ischemic stroke on DOAC treatment compared with warfarin treatment, to an 18% reduced rate of hospitalization for a GI bleed, compared with warfarin-treated patients. In the subgroup of patients who weighed less than 50 kg (110 pounds), the reductions ranged from a 41% cut in ischemic stroke on a DOAC compared with warfarin to a 24% relative reduction in the rate of hospitalization for a major bleed, a difference that just reached statistical significance. The outcome of hospitalization for a GI bleed showed no significant between-group difference among very-low-weight patients, but the rates of intracranial hemorrhage and all-cause death also showed statistically significant lower rates among DOAC-treated patients.
Nearly two-thirds of the patients on a DOAC received the label-appropriate dose of the drug, but 31% received a dosage that was below the labeled level while 4% received a dosage above the labeled level. An analysis that divided the NOAC patients by the appropriateness of their treatment dosages showed that patients on the correct dosages fared best. For example, in the total cohort of patients who weighed 60 kg or less, those on the correct DOAC dosage had a 9.1% rate of the combined endpoint. Patients on a low DOAC dosage did about as well as did the patients on warfarin, with a combined event rate of 11.6% in each of these subgroups. The worst outcomes occurred among the small number of patients on an inappropriately-high DOAC dosage, with a combined event rate of 15.4%. The researchers found a similar pattern among patients who weighed less than 50 kg.
Dr. Lee had no disclosures.
SOURCE: Lee SR et al. HRS 2019, Abstract S-AB30-05.
SAN FRANCISCO – The direct-acting anticoagulants, as a class, were more effective and at least as safe as warfarin in low-weight and very-low-weight patients with atrial fibrillation in an adjusted analysis of real-world outcomes data from more than 21,000 Korean patients.
The analysis also showed that the direct-acting oral anticoagulants (DOACs) had the best safety and efficacy on low-weight patients when used at the labeled dosages, with blunted efficacy and safety at dosages that either exceeded or fell short of labeled levels, So-Ryoung Lee, MD, said at the annual scientific sessions of the Heart Rhythm Society.
The overall superiority of DOACs by both efficacy and safety also generally extended to the subgroup of very-low-weight patients, those with weights of less than 50 kg. In this subgroup, which was 28% of the total population studied, the composite adverse event outcome occurred 33% less often among patients treated with a DOAC relative to patients treated with warfarin, a statistically significant difference, said Dr. Lee, a cardiologist at Seoul (South Korea) National University Hospital. Among all patients with weights of 60 kg (132 pounds) or less, the composite outcome occurred 34% less often in the DOAC-treated patients relative to the warfarin-treated patients, also a statistically significant difference.
Dr. Lee and colleagues used a Korean National Health Insurance database that included information on more than 600,000 adults with atrial fibrillation (AFib) as of January 2013. The researchers whittled this down to 21,678 patients who began for the first time treatment with an oral anticoagulant starting during or after January 2014; had no history of a stroke, intracranial hemorrhage, or gastrointestinal bleed; and weighed no more than 60 kg. This cohort included 7,575 (35%) who received warfarin treatment, and 14,103 (65%) who received a DOAC. Within the DOAC-treated group, 42% received rivaroxaban (Xarelto), 26% dabigatran (Pradaxa), 24% apixaban (Eliquis), and 8% edoxaban (Savaysa).
To account for baseline differences in demographics and comorbidities between the patients treated with a DOAC and those who received warfarin, Dr. Lee and her associates did propensity score adjustment, which resulted in similar cohorts of 6,692 patients treated with warfarin and 12,810 patients treated with a DOAC. The average age of these patients was 73 years, a third were men, and the average body mass index was just over 22 kg/m2.
The events that the researchers tallied during follow-up through December 2016 included rates of all-cause death, ischemic stroke, intracranial hemorrhage, hospitalization for GI bleeding, hospitalization for major bleeding, and the composite of these five outcomes.
In the propensity-score adjusted full cohort of all patients who weighed 60 kg or less, the rate of each of these five outcomes, as well as the composite outcome, occurred statistically significantly less often among the DOAC-treated patients than in those on warfarin. The reductions ranged from a 41% lower incidence of ischemic stroke on DOAC treatment compared with warfarin treatment, to an 18% reduced rate of hospitalization for a GI bleed, compared with warfarin-treated patients. In the subgroup of patients who weighed less than 50 kg (110 pounds), the reductions ranged from a 41% cut in ischemic stroke on a DOAC compared with warfarin to a 24% relative reduction in the rate of hospitalization for a major bleed, a difference that just reached statistical significance. The outcome of hospitalization for a GI bleed showed no significant between-group difference among very-low-weight patients, but the rates of intracranial hemorrhage and all-cause death also showed statistically significant lower rates among DOAC-treated patients.
Nearly two-thirds of the patients on a DOAC received the label-appropriate dose of the drug, but 31% received a dosage that was below the labeled level while 4% received a dosage above the labeled level. An analysis that divided the NOAC patients by the appropriateness of their treatment dosages showed that patients on the correct dosages fared best. For example, in the total cohort of patients who weighed 60 kg or less, those on the correct DOAC dosage had a 9.1% rate of the combined endpoint. Patients on a low DOAC dosage did about as well as did the patients on warfarin, with a combined event rate of 11.6% in each of these subgroups. The worst outcomes occurred among the small number of patients on an inappropriately-high DOAC dosage, with a combined event rate of 15.4%. The researchers found a similar pattern among patients who weighed less than 50 kg.
Dr. Lee had no disclosures.
SOURCE: Lee SR et al. HRS 2019, Abstract S-AB30-05.
REPORTING FROM HEART RHYTHM 2019
MADIT-CHIC: CRT aids patients with chemotherapy-induced cardiomyopathy
SAN FRANCISCO – Patients with cardiomyopathy secondary to cancer chemotherapy who qualified for cardiac resynchronization therapy (CRT) by having a wide QRS interval showed a virtually uniform, positive response to this treatment in a multicenter study with 30 patients.
This is the first time this therapy has been prospectively assessed in this patient population.
The results “show for the first time that patients with chemotherapy-induced cardiomyopathy [CHIC] who meet criteria for CRT show significant improvement in left ventricular function and clinical symptoms in the short term” during follow-up of 6 months, Jagmeet P. Singh, MD, said at the annual scientific sessions of the Heart Rhythm Society.
Dr. Singh acknowledged that, with 30 patients, the study was small, uncontrolled, had a brief follow-up of 6 months, and was highly selective. It took collaborating investigators at 12 U.S. centers more than 3.5 years to find the 30 participating patients, who had to meet very specific criteria designed to identify true CHIC. Nonetheless, Dr. Singh considered the results convincing enough to shift practice.
Based on the results, “I would certainly feel comfortable using CRT in patients with CHIC,” said Dr. Singh, associate chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. “If a patient has CHIC with a wide QRS interval and evidence for a conduction defect on their ECG, they are a great candidate for CRT. The results highlight that there is a cohort of patients who develop cardiomyopathy after chemotherapy, and these patients are often written off” and until now have generally received little follow-up for their potential development of cardiomyopathy. Dr. Singh expressed hope that the recent emergence of cardio-oncology as a subspecialty will focus attention on CHIC patients.
The MADIT-CHIC (Multicenter Automatic Defibrillator Implantation Trial – Chemotherapy-Induced Cardiomyopathy) study enrolled patients with a history of exposure to a cancer chemotherapy regimen known to cause cardiomyopathy who had no history of heart failure prior to the chemotherapy. All patients had developed clinically apparent heart failure (New York Heart Association functional class II, III, or IV) at least 6 months after completing chemotherapy, had no other apparent cause of the cardiomyopathy as ascertained by a cardio-oncologist, and were on guideline-directed medical therapy. Enrolled patients also had to have a class I or II indication for CRT, with a left ventricular ejection fraction of 35% or less, a QRS interval of at least 120 milliseconds, sinus rhythm and left bundle branch block, or no left bundle branch block and a QRS of at least 150 milliseconds.
Just over three-quarters of the patients had received an anthracycline drug, and 73% had a history of breast cancer, 20% a history of leukemia or lymphoma, and 7% had a history of sarcoma. The patients averaged 64 years of age, and 87% were women. CRT placement occurred 18-256 months after the end of chemotherapy, with a median of 188 months.
The study’s primary endpoint was the change in left ventricular ejection fraction after 6 months, which increased from an average of 28% at baseline to 39% at follow-up, a statistically significant change. Ejection fraction increased in 29 of the 30 patients, with one patient showing a flat response to CRT. Cardiac function and geometry significantly improved by seven other measures, including left ventricular mass and left atrial volume, and the improved ejection fraction was consistent across several subgroup analyses. Patients’ NYHA functional class improved by at least one level in 41% of patients, and 83% of the patients stopped showing clinical features of heart failure after 6 months on CRT.
MADIT-CHIC received funding from Boston Scientific. Dr. Singh has been a consultant to Abbott, Back Beat, Biotronik, Boston Scientific, EBR, Impulse Dynamics, Medtronic, Microport, St. Jude, and Toray, and he has received research support from Abbott and Boston Scientific.
SOURCE: Singh JP et al. HRS 2019, Abstract S-LBCT02-04.
No guideline currently addresses using cardiac resynchronization therapy to treat chemotherapy-induced cardiomyopathy. The findings from MADIT-CHIC showed a striking benefit from treatment with cardiac resynchronization therapy of a magnitude we would expect to see in patients with nonischemic cardiomyopathy. Patients showed improvements in all measures of cardiac performance.
It appears that CHIC can take as long as decades to appear in a patient, but we now need to have a high level of suspicion for this complication. We need to come up with better ways to monitor development of CHIC in patients who have received cancer chemotherapy so that we can give eligible patients this beneficial treatment. We can be optimistic about the potential for benefit from CRT in these patients.
Kenneth A. Ellenbogen, MD , is chief of cardiology and a professor of medicine at Virginia Commonwealth University in Richmond, Va. He has been a consultant to Boston Scientific, Medtronic, and St. Jude; he has received honoraria from Biotronik; and he has received research funding from Boston Scientific and Medtronic. He made these comments as the designated discussant for the MADIT-CHIC report.
No guideline currently addresses using cardiac resynchronization therapy to treat chemotherapy-induced cardiomyopathy. The findings from MADIT-CHIC showed a striking benefit from treatment with cardiac resynchronization therapy of a magnitude we would expect to see in patients with nonischemic cardiomyopathy. Patients showed improvements in all measures of cardiac performance.
It appears that CHIC can take as long as decades to appear in a patient, but we now need to have a high level of suspicion for this complication. We need to come up with better ways to monitor development of CHIC in patients who have received cancer chemotherapy so that we can give eligible patients this beneficial treatment. We can be optimistic about the potential for benefit from CRT in these patients.
Kenneth A. Ellenbogen, MD , is chief of cardiology and a professor of medicine at Virginia Commonwealth University in Richmond, Va. He has been a consultant to Boston Scientific, Medtronic, and St. Jude; he has received honoraria from Biotronik; and he has received research funding from Boston Scientific and Medtronic. He made these comments as the designated discussant for the MADIT-CHIC report.
No guideline currently addresses using cardiac resynchronization therapy to treat chemotherapy-induced cardiomyopathy. The findings from MADIT-CHIC showed a striking benefit from treatment with cardiac resynchronization therapy of a magnitude we would expect to see in patients with nonischemic cardiomyopathy. Patients showed improvements in all measures of cardiac performance.
It appears that CHIC can take as long as decades to appear in a patient, but we now need to have a high level of suspicion for this complication. We need to come up with better ways to monitor development of CHIC in patients who have received cancer chemotherapy so that we can give eligible patients this beneficial treatment. We can be optimistic about the potential for benefit from CRT in these patients.
Kenneth A. Ellenbogen, MD , is chief of cardiology and a professor of medicine at Virginia Commonwealth University in Richmond, Va. He has been a consultant to Boston Scientific, Medtronic, and St. Jude; he has received honoraria from Biotronik; and he has received research funding from Boston Scientific and Medtronic. He made these comments as the designated discussant for the MADIT-CHIC report.
SAN FRANCISCO – Patients with cardiomyopathy secondary to cancer chemotherapy who qualified for cardiac resynchronization therapy (CRT) by having a wide QRS interval showed a virtually uniform, positive response to this treatment in a multicenter study with 30 patients.
This is the first time this therapy has been prospectively assessed in this patient population.
The results “show for the first time that patients with chemotherapy-induced cardiomyopathy [CHIC] who meet criteria for CRT show significant improvement in left ventricular function and clinical symptoms in the short term” during follow-up of 6 months, Jagmeet P. Singh, MD, said at the annual scientific sessions of the Heart Rhythm Society.
Dr. Singh acknowledged that, with 30 patients, the study was small, uncontrolled, had a brief follow-up of 6 months, and was highly selective. It took collaborating investigators at 12 U.S. centers more than 3.5 years to find the 30 participating patients, who had to meet very specific criteria designed to identify true CHIC. Nonetheless, Dr. Singh considered the results convincing enough to shift practice.
Based on the results, “I would certainly feel comfortable using CRT in patients with CHIC,” said Dr. Singh, associate chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. “If a patient has CHIC with a wide QRS interval and evidence for a conduction defect on their ECG, they are a great candidate for CRT. The results highlight that there is a cohort of patients who develop cardiomyopathy after chemotherapy, and these patients are often written off” and until now have generally received little follow-up for their potential development of cardiomyopathy. Dr. Singh expressed hope that the recent emergence of cardio-oncology as a subspecialty will focus attention on CHIC patients.
The MADIT-CHIC (Multicenter Automatic Defibrillator Implantation Trial – Chemotherapy-Induced Cardiomyopathy) study enrolled patients with a history of exposure to a cancer chemotherapy regimen known to cause cardiomyopathy who had no history of heart failure prior to the chemotherapy. All patients had developed clinically apparent heart failure (New York Heart Association functional class II, III, or IV) at least 6 months after completing chemotherapy, had no other apparent cause of the cardiomyopathy as ascertained by a cardio-oncologist, and were on guideline-directed medical therapy. Enrolled patients also had to have a class I or II indication for CRT, with a left ventricular ejection fraction of 35% or less, a QRS interval of at least 120 milliseconds, sinus rhythm and left bundle branch block, or no left bundle branch block and a QRS of at least 150 milliseconds.
Just over three-quarters of the patients had received an anthracycline drug, and 73% had a history of breast cancer, 20% a history of leukemia or lymphoma, and 7% had a history of sarcoma. The patients averaged 64 years of age, and 87% were women. CRT placement occurred 18-256 months after the end of chemotherapy, with a median of 188 months.
The study’s primary endpoint was the change in left ventricular ejection fraction after 6 months, which increased from an average of 28% at baseline to 39% at follow-up, a statistically significant change. Ejection fraction increased in 29 of the 30 patients, with one patient showing a flat response to CRT. Cardiac function and geometry significantly improved by seven other measures, including left ventricular mass and left atrial volume, and the improved ejection fraction was consistent across several subgroup analyses. Patients’ NYHA functional class improved by at least one level in 41% of patients, and 83% of the patients stopped showing clinical features of heart failure after 6 months on CRT.
MADIT-CHIC received funding from Boston Scientific. Dr. Singh has been a consultant to Abbott, Back Beat, Biotronik, Boston Scientific, EBR, Impulse Dynamics, Medtronic, Microport, St. Jude, and Toray, and he has received research support from Abbott and Boston Scientific.
SOURCE: Singh JP et al. HRS 2019, Abstract S-LBCT02-04.
SAN FRANCISCO – Patients with cardiomyopathy secondary to cancer chemotherapy who qualified for cardiac resynchronization therapy (CRT) by having a wide QRS interval showed a virtually uniform, positive response to this treatment in a multicenter study with 30 patients.
This is the first time this therapy has been prospectively assessed in this patient population.
The results “show for the first time that patients with chemotherapy-induced cardiomyopathy [CHIC] who meet criteria for CRT show significant improvement in left ventricular function and clinical symptoms in the short term” during follow-up of 6 months, Jagmeet P. Singh, MD, said at the annual scientific sessions of the Heart Rhythm Society.
Dr. Singh acknowledged that, with 30 patients, the study was small, uncontrolled, had a brief follow-up of 6 months, and was highly selective. It took collaborating investigators at 12 U.S. centers more than 3.5 years to find the 30 participating patients, who had to meet very specific criteria designed to identify true CHIC. Nonetheless, Dr. Singh considered the results convincing enough to shift practice.
Based on the results, “I would certainly feel comfortable using CRT in patients with CHIC,” said Dr. Singh, associate chief of cardiology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. “If a patient has CHIC with a wide QRS interval and evidence for a conduction defect on their ECG, they are a great candidate for CRT. The results highlight that there is a cohort of patients who develop cardiomyopathy after chemotherapy, and these patients are often written off” and until now have generally received little follow-up for their potential development of cardiomyopathy. Dr. Singh expressed hope that the recent emergence of cardio-oncology as a subspecialty will focus attention on CHIC patients.
The MADIT-CHIC (Multicenter Automatic Defibrillator Implantation Trial – Chemotherapy-Induced Cardiomyopathy) study enrolled patients with a history of exposure to a cancer chemotherapy regimen known to cause cardiomyopathy who had no history of heart failure prior to the chemotherapy. All patients had developed clinically apparent heart failure (New York Heart Association functional class II, III, or IV) at least 6 months after completing chemotherapy, had no other apparent cause of the cardiomyopathy as ascertained by a cardio-oncologist, and were on guideline-directed medical therapy. Enrolled patients also had to have a class I or II indication for CRT, with a left ventricular ejection fraction of 35% or less, a QRS interval of at least 120 milliseconds, sinus rhythm and left bundle branch block, or no left bundle branch block and a QRS of at least 150 milliseconds.
Just over three-quarters of the patients had received an anthracycline drug, and 73% had a history of breast cancer, 20% a history of leukemia or lymphoma, and 7% had a history of sarcoma. The patients averaged 64 years of age, and 87% were women. CRT placement occurred 18-256 months after the end of chemotherapy, with a median of 188 months.
The study’s primary endpoint was the change in left ventricular ejection fraction after 6 months, which increased from an average of 28% at baseline to 39% at follow-up, a statistically significant change. Ejection fraction increased in 29 of the 30 patients, with one patient showing a flat response to CRT. Cardiac function and geometry significantly improved by seven other measures, including left ventricular mass and left atrial volume, and the improved ejection fraction was consistent across several subgroup analyses. Patients’ NYHA functional class improved by at least one level in 41% of patients, and 83% of the patients stopped showing clinical features of heart failure after 6 months on CRT.
MADIT-CHIC received funding from Boston Scientific. Dr. Singh has been a consultant to Abbott, Back Beat, Biotronik, Boston Scientific, EBR, Impulse Dynamics, Medtronic, Microport, St. Jude, and Toray, and he has received research support from Abbott and Boston Scientific.
SOURCE: Singh JP et al. HRS 2019, Abstract S-LBCT02-04.
REPORTING FROM HEART RHYTHM 2019
Energy drinks increase BP and disrupt the heart’s electrical activity
Consuming caffeinated energy drinks leads to a prolonged QT interval and an increase in blood pressure, according to a study of young volunteers who had their hearts tested after drinking either energy drinks or placebo.
“Further investigation is warranted on whether an individual ingredient or a unique combination leads to the observed electrophysiological and hemodynamic changes,” wrote Sachin A. Shah of the University of the Pacific, Stockton, Calif., and coinvestigators. The study was published in the Journal of the American Heart Association.
To analyze electrocardiographic changes in the heart after consumption of 300 mg of caffeine plus other energy drink ingredients, the researchers assigned 34 healthy volunteers with an average age of 22 years to consume two 16-ounce bottles of either Drink A, a commercially available energy drink, Drink B, a different brand of energy drink, or a placebo drink for 3 days, followed by a 6-day washout period. Before and for 4 hours after consuming the beverages, volunteers had their hearts measured via ECG to test for differences in QT interval. Their blood pressures also were recorded.
Compared with placebo, the Drink A group had a 6.1 ms increase in QT interval and the Drink B group had a 7.7 ms rise. The maximum changes from baseline in corrected QT interval for Drink A, Drink B, and placebo were 17.9 ms, 19.6 ms, and 11.9 ms, respectively; both differences were statistically significant. Volunteers in Drink A and Drink B groups also had statistically significant increases of 5 mm Hg in systolic and 4 mm Hg in diastolic blood pressure after energy drink consumption, compared with placebo.
Both energy drinks used in the study contained caffeine (about 300 mg), taurine, glucuronolactone, and B vitamins. The investigators said that caffeine at doses under 400 mg is not expected to induce any electrocardiographic changes.
The coauthors noted their study’s limitations, including not investigating the effects of different doses and the possibility that consuming two 16-ounce bottles is an unrealistic real-world volume. That said, they noted that 16% of respondents to a 2,040-person survey admitted to consuming more than two energy drinks a day. In addition, though not every brand was tested, the researchers stated that, “the class of energy drinks, rather than one particular product, warrants use with caution.”
Dr. Shah reported serving as an expert witness in legal cases related to caffeinated energy drinks. The other authors reported no conflicts of interest.
SOURCE: Shah SA et al. J Am Heart Assoc. 2019 May 29.
Consuming caffeinated energy drinks leads to a prolonged QT interval and an increase in blood pressure, according to a study of young volunteers who had their hearts tested after drinking either energy drinks or placebo.
“Further investigation is warranted on whether an individual ingredient or a unique combination leads to the observed electrophysiological and hemodynamic changes,” wrote Sachin A. Shah of the University of the Pacific, Stockton, Calif., and coinvestigators. The study was published in the Journal of the American Heart Association.
To analyze electrocardiographic changes in the heart after consumption of 300 mg of caffeine plus other energy drink ingredients, the researchers assigned 34 healthy volunteers with an average age of 22 years to consume two 16-ounce bottles of either Drink A, a commercially available energy drink, Drink B, a different brand of energy drink, or a placebo drink for 3 days, followed by a 6-day washout period. Before and for 4 hours after consuming the beverages, volunteers had their hearts measured via ECG to test for differences in QT interval. Their blood pressures also were recorded.
Compared with placebo, the Drink A group had a 6.1 ms increase in QT interval and the Drink B group had a 7.7 ms rise. The maximum changes from baseline in corrected QT interval for Drink A, Drink B, and placebo were 17.9 ms, 19.6 ms, and 11.9 ms, respectively; both differences were statistically significant. Volunteers in Drink A and Drink B groups also had statistically significant increases of 5 mm Hg in systolic and 4 mm Hg in diastolic blood pressure after energy drink consumption, compared with placebo.
Both energy drinks used in the study contained caffeine (about 300 mg), taurine, glucuronolactone, and B vitamins. The investigators said that caffeine at doses under 400 mg is not expected to induce any electrocardiographic changes.
The coauthors noted their study’s limitations, including not investigating the effects of different doses and the possibility that consuming two 16-ounce bottles is an unrealistic real-world volume. That said, they noted that 16% of respondents to a 2,040-person survey admitted to consuming more than two energy drinks a day. In addition, though not every brand was tested, the researchers stated that, “the class of energy drinks, rather than one particular product, warrants use with caution.”
Dr. Shah reported serving as an expert witness in legal cases related to caffeinated energy drinks. The other authors reported no conflicts of interest.
SOURCE: Shah SA et al. J Am Heart Assoc. 2019 May 29.
Consuming caffeinated energy drinks leads to a prolonged QT interval and an increase in blood pressure, according to a study of young volunteers who had their hearts tested after drinking either energy drinks or placebo.
“Further investigation is warranted on whether an individual ingredient or a unique combination leads to the observed electrophysiological and hemodynamic changes,” wrote Sachin A. Shah of the University of the Pacific, Stockton, Calif., and coinvestigators. The study was published in the Journal of the American Heart Association.
To analyze electrocardiographic changes in the heart after consumption of 300 mg of caffeine plus other energy drink ingredients, the researchers assigned 34 healthy volunteers with an average age of 22 years to consume two 16-ounce bottles of either Drink A, a commercially available energy drink, Drink B, a different brand of energy drink, or a placebo drink for 3 days, followed by a 6-day washout period. Before and for 4 hours after consuming the beverages, volunteers had their hearts measured via ECG to test for differences in QT interval. Their blood pressures also were recorded.
Compared with placebo, the Drink A group had a 6.1 ms increase in QT interval and the Drink B group had a 7.7 ms rise. The maximum changes from baseline in corrected QT interval for Drink A, Drink B, and placebo were 17.9 ms, 19.6 ms, and 11.9 ms, respectively; both differences were statistically significant. Volunteers in Drink A and Drink B groups also had statistically significant increases of 5 mm Hg in systolic and 4 mm Hg in diastolic blood pressure after energy drink consumption, compared with placebo.
Both energy drinks used in the study contained caffeine (about 300 mg), taurine, glucuronolactone, and B vitamins. The investigators said that caffeine at doses under 400 mg is not expected to induce any electrocardiographic changes.
The coauthors noted their study’s limitations, including not investigating the effects of different doses and the possibility that consuming two 16-ounce bottles is an unrealistic real-world volume. That said, they noted that 16% of respondents to a 2,040-person survey admitted to consuming more than two energy drinks a day. In addition, though not every brand was tested, the researchers stated that, “the class of energy drinks, rather than one particular product, warrants use with caution.”
Dr. Shah reported serving as an expert witness in legal cases related to caffeinated energy drinks. The other authors reported no conflicts of interest.
SOURCE: Shah SA et al. J Am Heart Assoc. 2019 May 29.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Key clinical point:
Major finding: Compared with placebo, consuming two different energy drinks led to significant QT interval increases of 6.1 ms and 7.7 ms.
Study details: A randomized, double-blind crossover study of 34 healthy volunteers who had their hearts measured via electrocardiogram after consuming energy drink or placebo.
Disclosures: Dr. Shah reported serving as an expert witness in legal cases related to caffeinated energy drinks. The other authors reported no conflicts of interest.
Source: Shah SA et al. J Am Heart Assoc. 2019 May 29.
Warfarin boosts OA risk in Rotterdam Study
TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.
A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.
In a previous genetic study, she and her coinvestigators identified two genetic variants that result in loss of function of matrix Gla protein (MGP), a key inhibitor of cartilage calcification. They showed that the presence of these alleles was associated with a significantly increased risk of hand OA, which makes sense because increased calcification within a vulnerable joint promotes OA.
“The interesting thing here is that, in order for MGP to inhibit calcification, it needs to be gamma-carboxylated by vitamin K. If it’s not gamma-carboxylated it cannot inhibit calcification,” Ms. Boer said at the meeting sponsored by the Osteoarthritis Research Society International.
This observation led her to hypothesize that patients on warfarin or other vitamin K antagonists might have an increased risk of developing new-onset OA or, if they already had OA, of experiencing disease progression, since their medication inhibits MGP. To test this hypothesis, she and her coinvestigators turned to the landmark Rotterdam Study, a prospective, population-based cohort study of 15,000 participants, ongoing since 1990. Two large cohorts within the study had data available on the incidence and progression of radiographic knee and hip OA, one group over the course of 5 years of follow-up, the other with 10 years.
Serial x-rays of 8,845 knee joints were available, including 657 of warfarin users. Their rate of incident or progressive knee OA was 13%, compared with 5.9% in the nonusers in an analysis adjusted for age, sex, BMI, baseline OA status, and time between study visits.
In a similar vein, the rate of incident or progressive hip OA was 12% in the warfarin users, compared with 3.1% in nonusers.
About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.
There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.
Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.
She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.
TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.
A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.
In a previous genetic study, she and her coinvestigators identified two genetic variants that result in loss of function of matrix Gla protein (MGP), a key inhibitor of cartilage calcification. They showed that the presence of these alleles was associated with a significantly increased risk of hand OA, which makes sense because increased calcification within a vulnerable joint promotes OA.
“The interesting thing here is that, in order for MGP to inhibit calcification, it needs to be gamma-carboxylated by vitamin K. If it’s not gamma-carboxylated it cannot inhibit calcification,” Ms. Boer said at the meeting sponsored by the Osteoarthritis Research Society International.
This observation led her to hypothesize that patients on warfarin or other vitamin K antagonists might have an increased risk of developing new-onset OA or, if they already had OA, of experiencing disease progression, since their medication inhibits MGP. To test this hypothesis, she and her coinvestigators turned to the landmark Rotterdam Study, a prospective, population-based cohort study of 15,000 participants, ongoing since 1990. Two large cohorts within the study had data available on the incidence and progression of radiographic knee and hip OA, one group over the course of 5 years of follow-up, the other with 10 years.
Serial x-rays of 8,845 knee joints were available, including 657 of warfarin users. Their rate of incident or progressive knee OA was 13%, compared with 5.9% in the nonusers in an analysis adjusted for age, sex, BMI, baseline OA status, and time between study visits.
In a similar vein, the rate of incident or progressive hip OA was 12% in the warfarin users, compared with 3.1% in nonusers.
About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.
There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.
Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.
She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.
TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.
A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.
In a previous genetic study, she and her coinvestigators identified two genetic variants that result in loss of function of matrix Gla protein (MGP), a key inhibitor of cartilage calcification. They showed that the presence of these alleles was associated with a significantly increased risk of hand OA, which makes sense because increased calcification within a vulnerable joint promotes OA.
“The interesting thing here is that, in order for MGP to inhibit calcification, it needs to be gamma-carboxylated by vitamin K. If it’s not gamma-carboxylated it cannot inhibit calcification,” Ms. Boer said at the meeting sponsored by the Osteoarthritis Research Society International.
This observation led her to hypothesize that patients on warfarin or other vitamin K antagonists might have an increased risk of developing new-onset OA or, if they already had OA, of experiencing disease progression, since their medication inhibits MGP. To test this hypothesis, she and her coinvestigators turned to the landmark Rotterdam Study, a prospective, population-based cohort study of 15,000 participants, ongoing since 1990. Two large cohorts within the study had data available on the incidence and progression of radiographic knee and hip OA, one group over the course of 5 years of follow-up, the other with 10 years.
Serial x-rays of 8,845 knee joints were available, including 657 of warfarin users. Their rate of incident or progressive knee OA was 13%, compared with 5.9% in the nonusers in an analysis adjusted for age, sex, BMI, baseline OA status, and time between study visits.
In a similar vein, the rate of incident or progressive hip OA was 12% in the warfarin users, compared with 3.1% in nonusers.
About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.
There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.
Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.
She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.
REPORTING FROM OARSI 2019
FDA updates warning about Impella RP System
The Food and Drug Administration has reported that the higher postapproval mortality rates seen with Abiomed’s Impella RP System seem concentrated in a certain subgroup of patients only, according to a letter to health care providers.
The letter updates one from February regarding the observation of higher postapproval mortality rates with the temporary right heart pump.
This subgroup, which did not qualify for premarket clinical studies, was more likely to have been in cardiogenic shock for longer than 48 hours, experienced a cardiac arrest, or suffered a preimplant hypoxic or ischemic neurologic event prior to receiving the device, the FDA suggested in this new letter to health care providers. The 30-day survival rate in this subgroup within a postapproval study (PAS) was 10.7% (3 out of 28), while that among patients who would have qualified for the premarket clinical studies was 64.3% (9 of 14), according to the most recent interim results of that study. The rate among patients who would have qualified for premarket studies is similar to that seen among those premarket studies (73.4%); the overall 30-day survival rate in this PAS was 28.6%.
The FDA said that, based on these analyses, it still believes the benefits outweigh the risks when the Impella RP System is “used for the currently approved indication in appropriately selected patients.”
The FDA advises that health care providers review the device’s revised labeling, which now includes a checklist to help understand which patients could benefit the most. It also advises providers to promptly report any adverse events through MedWatch, which can help the FDA identify and understand the risks associated with the Impella RP System.
More information can be found in the FDA’s letter to health care providers, which is available on the FDA website.
The Food and Drug Administration has reported that the higher postapproval mortality rates seen with Abiomed’s Impella RP System seem concentrated in a certain subgroup of patients only, according to a letter to health care providers.
The letter updates one from February regarding the observation of higher postapproval mortality rates with the temporary right heart pump.
This subgroup, which did not qualify for premarket clinical studies, was more likely to have been in cardiogenic shock for longer than 48 hours, experienced a cardiac arrest, or suffered a preimplant hypoxic or ischemic neurologic event prior to receiving the device, the FDA suggested in this new letter to health care providers. The 30-day survival rate in this subgroup within a postapproval study (PAS) was 10.7% (3 out of 28), while that among patients who would have qualified for the premarket clinical studies was 64.3% (9 of 14), according to the most recent interim results of that study. The rate among patients who would have qualified for premarket studies is similar to that seen among those premarket studies (73.4%); the overall 30-day survival rate in this PAS was 28.6%.
The FDA said that, based on these analyses, it still believes the benefits outweigh the risks when the Impella RP System is “used for the currently approved indication in appropriately selected patients.”
The FDA advises that health care providers review the device’s revised labeling, which now includes a checklist to help understand which patients could benefit the most. It also advises providers to promptly report any adverse events through MedWatch, which can help the FDA identify and understand the risks associated with the Impella RP System.
More information can be found in the FDA’s letter to health care providers, which is available on the FDA website.
The Food and Drug Administration has reported that the higher postapproval mortality rates seen with Abiomed’s Impella RP System seem concentrated in a certain subgroup of patients only, according to a letter to health care providers.
The letter updates one from February regarding the observation of higher postapproval mortality rates with the temporary right heart pump.
This subgroup, which did not qualify for premarket clinical studies, was more likely to have been in cardiogenic shock for longer than 48 hours, experienced a cardiac arrest, or suffered a preimplant hypoxic or ischemic neurologic event prior to receiving the device, the FDA suggested in this new letter to health care providers. The 30-day survival rate in this subgroup within a postapproval study (PAS) was 10.7% (3 out of 28), while that among patients who would have qualified for the premarket clinical studies was 64.3% (9 of 14), according to the most recent interim results of that study. The rate among patients who would have qualified for premarket studies is similar to that seen among those premarket studies (73.4%); the overall 30-day survival rate in this PAS was 28.6%.
The FDA said that, based on these analyses, it still believes the benefits outweigh the risks when the Impella RP System is “used for the currently approved indication in appropriately selected patients.”
The FDA advises that health care providers review the device’s revised labeling, which now includes a checklist to help understand which patients could benefit the most. It also advises providers to promptly report any adverse events through MedWatch, which can help the FDA identify and understand the risks associated with the Impella RP System.
More information can be found in the FDA’s letter to health care providers, which is available on the FDA website.
CABANA: Heart failure patients got biggest bang from AFib ablation
SAN FRANCISCO – Catheter ablation of atrial fibrillation (AFib) in the roughly one-third of patients with heart failure enrolled in the CABANA multicenter, randomized trial produced striking, statistically significant improvements both in the study’s primary, combined endpoint and in all-cause mortality in intention-to-treat analyses.
These findings, from prespecified secondary analyses, contrasted with the study’s overall result, which showed no benefit in the primary endpoint analysis in the total study population of 2,204 patients with AFib (JAMA. 2019 Apr 2;321[13]:1261-74). They are also at odds with the primary endpoint result in the two-thirds of enrolled patients without heart failure, which showed no significant between-group differences in these two outcome measures among the patients assigned to the catheter ablation arm and the study’s control, which was medical management arm.
Among the 778 AFib patients enrolled in CABANA with any form of heart failure (35% of the total study enrollment), the incidence of the study’s primary endpoint – the combined rate of death, disabling stroke, serious bleeding, or cardiac arrest during a median follow-up of slightly more than 4 years – was 36% lower among the catheter-ablated heart failure patients than in the heart failure patients assigned to medical treatment, according to an intention-to-treat analysis, which was a statistically significant difference. The incidence of all-cause mortality during follow-up was 43% lower in the ablated heart failure patients, compared with the controls, Douglas L. Packer, MD, said at the annual scientific sessions of the Heart Rhythm Society.
In contrast, among enrolled patients without heart failure, the intention-to-treat primary endpoint was 6% higher in the ablated patients, and all-cause mortality was a relative 27% higher, although neither difference was statistically significant.
It’s a “little surprising” that the results showed this much benefit in the patients with heart failure, said Dr. Packer, professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of the CABANA (Catheter Ablation vs Anti-Arrhythmic Drug Therapy for Atrial Fibrillation) trial. “I think these data confirm the results of the CASTLE-AF trial, but without some of the glitches some people have cited” about that study, such as concerns about a high level of patient selection in CASTLE-AF and its relatively modest number of enrolled patients, he said in an interview.
The CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) study, run entirely in patients with heart failure with reduced ejection fraction and AFib, showed a statistically significant improvement in patient survival and heart failure hospitalization after catheter ablation compared with medical management (N Engl J Med. 2018 Feb 1;378[5]:417-27). Prior to the CASTLE-AF report, results from several other small studies (J Interv Card Electrophysiol. 2018 Oct;53[1]:19-29), as well as those from the AATAC trial (Circulation. 2016 Apr 26;133[17]:1637-44), also showed consistent evidence for benefit from catheter ablation in patients with heart failure and AFib, noted CABANA coinvestigator Jonathan P. Piccini, MD, during a separate talk at the meeting.
“The improvement of cardiovascular outcomes with ablation in patients with heart failure and AFib is consistent across multiple trials, at least with respect to heart failure with reduced ejection fraction” concluded Dr. Piccini, a cardiac electrophysiologist at Duke University in Durham, N.C.
As a result of the new heart failure analysis, “I think the guidelines will change,” predicted Dr. Packer, with catheter ablation receiving a firmer endorsement for patients with heart failure the next time U.S. guidelines for heart failure and AFib management are updated. The findings say “there is substantial benefit of catheter ablation in heart failure patients, but I don’t think our findings lessen the utility of ablation in patients without heart failure,” he stressed. Even patients without heart failure showed reduction in AFib burden and improvement in quality of life that were similar to what was seen in the heart failure patients.
The new report from CABANA of benefit from AFib catheter ablation in patients with heart failure “absolutely advances the evidence,” commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern University in Chicago. “A number of us were quite circumspect about this based on the CASTLE-AF data, but the new CABANA analyses have addressed our anxiety that the CASTLE-AF results were just by chance.” The new CABANA analyses “may not confirm CASTLE-AF, but it enriches the conversation and makes it possible that we are seeing benefit in some patients with heart failure who get ablated.”
Dr. Yancy, who chaired the most recent update to the U.S. heart failure management guideline (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803) stopped short of saying that the cumulative evidence now supports a guideline change, but he acknowledged in an interview that the evidence could legitimately influence practice. Catheter ablation should now be “strongly considered” in patients with heart failure and AFib, he said, although he also had three qualifications for opting for this approach: Patients must already be on guideline-directed medical therapy for their heart failure, the catheter ablation needs to be performed by an experienced and skilled operator, and follow-up surveillance must focus on both the patient’s AFib and heart failure. “It’s absolutely appropriate to consider catheter ablation” for heart failure patients, but the evidence is not yet there for guideline change, Dr. Yancy concluded.
It remains uncertain why catheter ablation of AFib should be more effective in patients with heart failure than in those without. Dr. Packer speculated that one reason may be the heart rate reduction that AFib ablation produces may especially benefit heart failure patients. An additional helpful effect of ablation in heart failure patients may be reducing heart rate variability. Another notable finding of the new analysis was that 79% of patients with heart failure in CABANA had heart failure with preserved ejection fraction, with a left ventricular ejection fraction of at least 50%. “Getting rid of AFib in patients with heart failure with preserved ejection fraction will be more important than we have thought,” Dr. Packer said.
Other new CABANA analyses presented for the first time in separate talks at the meeting also showed that, while catheter ablation had no meaningful difference in effect on outcomes based on the sex of patients, both age and minority ethnic and racial status appeared to make a substantial difference. For CABANA’s primary endpoint, catheter ablation was especially effective for improving outcomes in patients 64 years old or younger, and the analysis showed a signal of possibly worse outcomes in patients who were at least 75 years old. The “substantially” better outcomes in minority-group patients represented the largest between-group difference among subgroups seen in CABANA and is a “big deal,” said Dr. Packer, who predicted that future catheter ablation use will likely rise in patients with heart failure, in younger patients, and in minority patients.
Dr. Piccini noted that, “it’s possible that CABANA identified some patient subgroups that do really well after ablation, but the problem is that, in the United States, we now often don’t treat” minority patients or those with reduced left ventricular ejection fractions with ablation, according to recent registry findings.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and/or received research funding from these four companies, as well as numerous drug and device companies, and has a financial interest in a licensed AFib mapping technology. Dr. Piccini has ties Boston Scientific, Medtronic, and numerous other drug and device companies, and disclosed an unspecified relationship with GlaxoSmithKline. Dr. Yancy disclosed an unspecified relationship with Abbott Laboratories.
SOURCE: Packer DL. Heart Rhythm 2019, Abstract S-AB14-06.
SAN FRANCISCO – Catheter ablation of atrial fibrillation (AFib) in the roughly one-third of patients with heart failure enrolled in the CABANA multicenter, randomized trial produced striking, statistically significant improvements both in the study’s primary, combined endpoint and in all-cause mortality in intention-to-treat analyses.
These findings, from prespecified secondary analyses, contrasted with the study’s overall result, which showed no benefit in the primary endpoint analysis in the total study population of 2,204 patients with AFib (JAMA. 2019 Apr 2;321[13]:1261-74). They are also at odds with the primary endpoint result in the two-thirds of enrolled patients without heart failure, which showed no significant between-group differences in these two outcome measures among the patients assigned to the catheter ablation arm and the study’s control, which was medical management arm.
Among the 778 AFib patients enrolled in CABANA with any form of heart failure (35% of the total study enrollment), the incidence of the study’s primary endpoint – the combined rate of death, disabling stroke, serious bleeding, or cardiac arrest during a median follow-up of slightly more than 4 years – was 36% lower among the catheter-ablated heart failure patients than in the heart failure patients assigned to medical treatment, according to an intention-to-treat analysis, which was a statistically significant difference. The incidence of all-cause mortality during follow-up was 43% lower in the ablated heart failure patients, compared with the controls, Douglas L. Packer, MD, said at the annual scientific sessions of the Heart Rhythm Society.
In contrast, among enrolled patients without heart failure, the intention-to-treat primary endpoint was 6% higher in the ablated patients, and all-cause mortality was a relative 27% higher, although neither difference was statistically significant.
It’s a “little surprising” that the results showed this much benefit in the patients with heart failure, said Dr. Packer, professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of the CABANA (Catheter Ablation vs Anti-Arrhythmic Drug Therapy for Atrial Fibrillation) trial. “I think these data confirm the results of the CASTLE-AF trial, but without some of the glitches some people have cited” about that study, such as concerns about a high level of patient selection in CASTLE-AF and its relatively modest number of enrolled patients, he said in an interview.
The CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) study, run entirely in patients with heart failure with reduced ejection fraction and AFib, showed a statistically significant improvement in patient survival and heart failure hospitalization after catheter ablation compared with medical management (N Engl J Med. 2018 Feb 1;378[5]:417-27). Prior to the CASTLE-AF report, results from several other small studies (J Interv Card Electrophysiol. 2018 Oct;53[1]:19-29), as well as those from the AATAC trial (Circulation. 2016 Apr 26;133[17]:1637-44), also showed consistent evidence for benefit from catheter ablation in patients with heart failure and AFib, noted CABANA coinvestigator Jonathan P. Piccini, MD, during a separate talk at the meeting.
“The improvement of cardiovascular outcomes with ablation in patients with heart failure and AFib is consistent across multiple trials, at least with respect to heart failure with reduced ejection fraction” concluded Dr. Piccini, a cardiac electrophysiologist at Duke University in Durham, N.C.
As a result of the new heart failure analysis, “I think the guidelines will change,” predicted Dr. Packer, with catheter ablation receiving a firmer endorsement for patients with heart failure the next time U.S. guidelines for heart failure and AFib management are updated. The findings say “there is substantial benefit of catheter ablation in heart failure patients, but I don’t think our findings lessen the utility of ablation in patients without heart failure,” he stressed. Even patients without heart failure showed reduction in AFib burden and improvement in quality of life that were similar to what was seen in the heart failure patients.
The new report from CABANA of benefit from AFib catheter ablation in patients with heart failure “absolutely advances the evidence,” commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern University in Chicago. “A number of us were quite circumspect about this based on the CASTLE-AF data, but the new CABANA analyses have addressed our anxiety that the CASTLE-AF results were just by chance.” The new CABANA analyses “may not confirm CASTLE-AF, but it enriches the conversation and makes it possible that we are seeing benefit in some patients with heart failure who get ablated.”
Dr. Yancy, who chaired the most recent update to the U.S. heart failure management guideline (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803) stopped short of saying that the cumulative evidence now supports a guideline change, but he acknowledged in an interview that the evidence could legitimately influence practice. Catheter ablation should now be “strongly considered” in patients with heart failure and AFib, he said, although he also had three qualifications for opting for this approach: Patients must already be on guideline-directed medical therapy for their heart failure, the catheter ablation needs to be performed by an experienced and skilled operator, and follow-up surveillance must focus on both the patient’s AFib and heart failure. “It’s absolutely appropriate to consider catheter ablation” for heart failure patients, but the evidence is not yet there for guideline change, Dr. Yancy concluded.
It remains uncertain why catheter ablation of AFib should be more effective in patients with heart failure than in those without. Dr. Packer speculated that one reason may be the heart rate reduction that AFib ablation produces may especially benefit heart failure patients. An additional helpful effect of ablation in heart failure patients may be reducing heart rate variability. Another notable finding of the new analysis was that 79% of patients with heart failure in CABANA had heart failure with preserved ejection fraction, with a left ventricular ejection fraction of at least 50%. “Getting rid of AFib in patients with heart failure with preserved ejection fraction will be more important than we have thought,” Dr. Packer said.
Other new CABANA analyses presented for the first time in separate talks at the meeting also showed that, while catheter ablation had no meaningful difference in effect on outcomes based on the sex of patients, both age and minority ethnic and racial status appeared to make a substantial difference. For CABANA’s primary endpoint, catheter ablation was especially effective for improving outcomes in patients 64 years old or younger, and the analysis showed a signal of possibly worse outcomes in patients who were at least 75 years old. The “substantially” better outcomes in minority-group patients represented the largest between-group difference among subgroups seen in CABANA and is a “big deal,” said Dr. Packer, who predicted that future catheter ablation use will likely rise in patients with heart failure, in younger patients, and in minority patients.
Dr. Piccini noted that, “it’s possible that CABANA identified some patient subgroups that do really well after ablation, but the problem is that, in the United States, we now often don’t treat” minority patients or those with reduced left ventricular ejection fractions with ablation, according to recent registry findings.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and/or received research funding from these four companies, as well as numerous drug and device companies, and has a financial interest in a licensed AFib mapping technology. Dr. Piccini has ties Boston Scientific, Medtronic, and numerous other drug and device companies, and disclosed an unspecified relationship with GlaxoSmithKline. Dr. Yancy disclosed an unspecified relationship with Abbott Laboratories.
SOURCE: Packer DL. Heart Rhythm 2019, Abstract S-AB14-06.
SAN FRANCISCO – Catheter ablation of atrial fibrillation (AFib) in the roughly one-third of patients with heart failure enrolled in the CABANA multicenter, randomized trial produced striking, statistically significant improvements both in the study’s primary, combined endpoint and in all-cause mortality in intention-to-treat analyses.
These findings, from prespecified secondary analyses, contrasted with the study’s overall result, which showed no benefit in the primary endpoint analysis in the total study population of 2,204 patients with AFib (JAMA. 2019 Apr 2;321[13]:1261-74). They are also at odds with the primary endpoint result in the two-thirds of enrolled patients without heart failure, which showed no significant between-group differences in these two outcome measures among the patients assigned to the catheter ablation arm and the study’s control, which was medical management arm.
Among the 778 AFib patients enrolled in CABANA with any form of heart failure (35% of the total study enrollment), the incidence of the study’s primary endpoint – the combined rate of death, disabling stroke, serious bleeding, or cardiac arrest during a median follow-up of slightly more than 4 years – was 36% lower among the catheter-ablated heart failure patients than in the heart failure patients assigned to medical treatment, according to an intention-to-treat analysis, which was a statistically significant difference. The incidence of all-cause mortality during follow-up was 43% lower in the ablated heart failure patients, compared with the controls, Douglas L. Packer, MD, said at the annual scientific sessions of the Heart Rhythm Society.
In contrast, among enrolled patients without heart failure, the intention-to-treat primary endpoint was 6% higher in the ablated patients, and all-cause mortality was a relative 27% higher, although neither difference was statistically significant.
It’s a “little surprising” that the results showed this much benefit in the patients with heart failure, said Dr. Packer, professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of the CABANA (Catheter Ablation vs Anti-Arrhythmic Drug Therapy for Atrial Fibrillation) trial. “I think these data confirm the results of the CASTLE-AF trial, but without some of the glitches some people have cited” about that study, such as concerns about a high level of patient selection in CASTLE-AF and its relatively modest number of enrolled patients, he said in an interview.
The CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) study, run entirely in patients with heart failure with reduced ejection fraction and AFib, showed a statistically significant improvement in patient survival and heart failure hospitalization after catheter ablation compared with medical management (N Engl J Med. 2018 Feb 1;378[5]:417-27). Prior to the CASTLE-AF report, results from several other small studies (J Interv Card Electrophysiol. 2018 Oct;53[1]:19-29), as well as those from the AATAC trial (Circulation. 2016 Apr 26;133[17]:1637-44), also showed consistent evidence for benefit from catheter ablation in patients with heart failure and AFib, noted CABANA coinvestigator Jonathan P. Piccini, MD, during a separate talk at the meeting.
“The improvement of cardiovascular outcomes with ablation in patients with heart failure and AFib is consistent across multiple trials, at least with respect to heart failure with reduced ejection fraction” concluded Dr. Piccini, a cardiac electrophysiologist at Duke University in Durham, N.C.
As a result of the new heart failure analysis, “I think the guidelines will change,” predicted Dr. Packer, with catheter ablation receiving a firmer endorsement for patients with heart failure the next time U.S. guidelines for heart failure and AFib management are updated. The findings say “there is substantial benefit of catheter ablation in heart failure patients, but I don’t think our findings lessen the utility of ablation in patients without heart failure,” he stressed. Even patients without heart failure showed reduction in AFib burden and improvement in quality of life that were similar to what was seen in the heart failure patients.
The new report from CABANA of benefit from AFib catheter ablation in patients with heart failure “absolutely advances the evidence,” commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern University in Chicago. “A number of us were quite circumspect about this based on the CASTLE-AF data, but the new CABANA analyses have addressed our anxiety that the CASTLE-AF results were just by chance.” The new CABANA analyses “may not confirm CASTLE-AF, but it enriches the conversation and makes it possible that we are seeing benefit in some patients with heart failure who get ablated.”
Dr. Yancy, who chaired the most recent update to the U.S. heart failure management guideline (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803) stopped short of saying that the cumulative evidence now supports a guideline change, but he acknowledged in an interview that the evidence could legitimately influence practice. Catheter ablation should now be “strongly considered” in patients with heart failure and AFib, he said, although he also had three qualifications for opting for this approach: Patients must already be on guideline-directed medical therapy for their heart failure, the catheter ablation needs to be performed by an experienced and skilled operator, and follow-up surveillance must focus on both the patient’s AFib and heart failure. “It’s absolutely appropriate to consider catheter ablation” for heart failure patients, but the evidence is not yet there for guideline change, Dr. Yancy concluded.
It remains uncertain why catheter ablation of AFib should be more effective in patients with heart failure than in those without. Dr. Packer speculated that one reason may be the heart rate reduction that AFib ablation produces may especially benefit heart failure patients. An additional helpful effect of ablation in heart failure patients may be reducing heart rate variability. Another notable finding of the new analysis was that 79% of patients with heart failure in CABANA had heart failure with preserved ejection fraction, with a left ventricular ejection fraction of at least 50%. “Getting rid of AFib in patients with heart failure with preserved ejection fraction will be more important than we have thought,” Dr. Packer said.
Other new CABANA analyses presented for the first time in separate talks at the meeting also showed that, while catheter ablation had no meaningful difference in effect on outcomes based on the sex of patients, both age and minority ethnic and racial status appeared to make a substantial difference. For CABANA’s primary endpoint, catheter ablation was especially effective for improving outcomes in patients 64 years old or younger, and the analysis showed a signal of possibly worse outcomes in patients who were at least 75 years old. The “substantially” better outcomes in minority-group patients represented the largest between-group difference among subgroups seen in CABANA and is a “big deal,” said Dr. Packer, who predicted that future catheter ablation use will likely rise in patients with heart failure, in younger patients, and in minority patients.
Dr. Piccini noted that, “it’s possible that CABANA identified some patient subgroups that do really well after ablation, but the problem is that, in the United States, we now often don’t treat” minority patients or those with reduced left ventricular ejection fractions with ablation, according to recent registry findings.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and/or received research funding from these four companies, as well as numerous drug and device companies, and has a financial interest in a licensed AFib mapping technology. Dr. Piccini has ties Boston Scientific, Medtronic, and numerous other drug and device companies, and disclosed an unspecified relationship with GlaxoSmithKline. Dr. Yancy disclosed an unspecified relationship with Abbott Laboratories.
SOURCE: Packer DL. Heart Rhythm 2019, Abstract S-AB14-06.
REPORTING FROM HEART RHYTHM 2019
Key clinical point: Catheter ablation for atrial fibrillation is especially effective in patients with heart failure.
Major finding: Heart failure patients treated with catheter ablation had a 36% relative cut in the primary endpoint, compared with control patients.
Study details: CABANA, a multicenter, randomized trial with 2,204 patients, including 778 patients with heart failure.
Disclosures: CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and/or received research funding from these four companies, as well as numerous drug and device companies, and has a financial interest in a licensed AFib mapping technology. Source: Packer DL. Heart Rhythm 2019, Abstract S-AB14-06.
AFib on the rise in end-stage COPD patients hospitalized for exacerbations
Atrial fibrillation is being seen with increasing frequency in patients admitted to U.S. hospitals for exacerbations of end-stage chronic obstructive pulmonary disease, based on a retrospective analysis of data from the Nationwide Inpatient Sample.
The prevalence of atrial fibrillation (AFib) among patients with end-stage chronic obstructive pulmonary disease (COPD) on home oxygen who were admitted with COPD exacerbations increased from 12.9% in 2003 to 21.3% in 2014, according to Xiaochun Xiao of the department of health statistics at Second Military Medical University in Shanghai and colleagues.
Additionally, “we found that comorbid [AFib] was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation. Moreover, comorbid [AFib] was associated with adverse clinical outcomes, including increased in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke,” the researchers wrote in the study published in the journal CHEST.
Patients included in the study were aged at least 18 years, were diagnosed with end-stage COPD and on home oxygen, and were hospitalized because of a COPD-related exacerbation. Based on 1,345,270 weighted hospital admissions of adults with end-stage COPD on home oxygen who met the inclusion criteria for the study, 18.2% (244,488 admissions) of patients had AFib, and the prevalence of AFib in COPD patients increased over time from 2003 (12.9%) to 2014 (21.3%; P less than .0001).
Patients with AFib, compared with patients without AFib, were older (75.5 years vs. 69.6 years; P less than .0001) and more likely to be male (50.7% vs. 59.1%; P less than .0001) and white (80.9% vs. 74.4%; P less than .0001). Patients with AFib also had higher stroke risk reflected in higher CHA2DS2-VASc scores (3.26 vs. 2.45; P less than .0001), and higher likelihood of in-hospital mortality and readmission reflected in Elixhauser scores greater than or equal to 4 (51.2% vs. 35.6%).
In addition, the prevalence of AFib increased with increasing income. Larger hospitals in terms of bed size, urban environment, and Medicare insurance status also were associated with a higher AFib prevalence.
AFib was associated with an increased cost of $1,415 and an increased length of stay of 0.6 days after adjustment for potential confounders. AFib also predicted risk for several adverse events, including stroke (odds ratio, 1.80; in-hospital death, [OR, 1.54]), invasive mechanical ventilation (OR, 1.37), sepsis (OR, 1.23), noninvasive mechanical ventilation (OR, 1.14), acute kidney injury (OR, 1.09), and acute respiratory failure (OR, 1.09).
The researchers noted the database could have potentially overinflated AFib prevalence, as they could not differentiate index admissions and readmissions. The database also does not contain information about secondary diagnoses codes present on admission, which could make it difficult to identify adverse events that occurred during hospitalization.
“Our findings should prompt further efforts to identify the reasons for increased [AFib] prevalence and provide better management strategies for end-stage COPD patients comorbid with [AFib],” the researchers concluded.
This study was funded by a grant from the Fourth Round of the Shanghai 3-year Action Plan on Public Health Discipline and Talent Program. The authors reported no relevant conflict of interest.
SOURCE: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.
Atrial fibrillation is being seen with increasing frequency in patients admitted to U.S. hospitals for exacerbations of end-stage chronic obstructive pulmonary disease, based on a retrospective analysis of data from the Nationwide Inpatient Sample.
The prevalence of atrial fibrillation (AFib) among patients with end-stage chronic obstructive pulmonary disease (COPD) on home oxygen who were admitted with COPD exacerbations increased from 12.9% in 2003 to 21.3% in 2014, according to Xiaochun Xiao of the department of health statistics at Second Military Medical University in Shanghai and colleagues.
Additionally, “we found that comorbid [AFib] was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation. Moreover, comorbid [AFib] was associated with adverse clinical outcomes, including increased in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke,” the researchers wrote in the study published in the journal CHEST.
Patients included in the study were aged at least 18 years, were diagnosed with end-stage COPD and on home oxygen, and were hospitalized because of a COPD-related exacerbation. Based on 1,345,270 weighted hospital admissions of adults with end-stage COPD on home oxygen who met the inclusion criteria for the study, 18.2% (244,488 admissions) of patients had AFib, and the prevalence of AFib in COPD patients increased over time from 2003 (12.9%) to 2014 (21.3%; P less than .0001).
Patients with AFib, compared with patients without AFib, were older (75.5 years vs. 69.6 years; P less than .0001) and more likely to be male (50.7% vs. 59.1%; P less than .0001) and white (80.9% vs. 74.4%; P less than .0001). Patients with AFib also had higher stroke risk reflected in higher CHA2DS2-VASc scores (3.26 vs. 2.45; P less than .0001), and higher likelihood of in-hospital mortality and readmission reflected in Elixhauser scores greater than or equal to 4 (51.2% vs. 35.6%).
In addition, the prevalence of AFib increased with increasing income. Larger hospitals in terms of bed size, urban environment, and Medicare insurance status also were associated with a higher AFib prevalence.
AFib was associated with an increased cost of $1,415 and an increased length of stay of 0.6 days after adjustment for potential confounders. AFib also predicted risk for several adverse events, including stroke (odds ratio, 1.80; in-hospital death, [OR, 1.54]), invasive mechanical ventilation (OR, 1.37), sepsis (OR, 1.23), noninvasive mechanical ventilation (OR, 1.14), acute kidney injury (OR, 1.09), and acute respiratory failure (OR, 1.09).
The researchers noted the database could have potentially overinflated AFib prevalence, as they could not differentiate index admissions and readmissions. The database also does not contain information about secondary diagnoses codes present on admission, which could make it difficult to identify adverse events that occurred during hospitalization.
“Our findings should prompt further efforts to identify the reasons for increased [AFib] prevalence and provide better management strategies for end-stage COPD patients comorbid with [AFib],” the researchers concluded.
This study was funded by a grant from the Fourth Round of the Shanghai 3-year Action Plan on Public Health Discipline and Talent Program. The authors reported no relevant conflict of interest.
SOURCE: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.
Atrial fibrillation is being seen with increasing frequency in patients admitted to U.S. hospitals for exacerbations of end-stage chronic obstructive pulmonary disease, based on a retrospective analysis of data from the Nationwide Inpatient Sample.
The prevalence of atrial fibrillation (AFib) among patients with end-stage chronic obstructive pulmonary disease (COPD) on home oxygen who were admitted with COPD exacerbations increased from 12.9% in 2003 to 21.3% in 2014, according to Xiaochun Xiao of the department of health statistics at Second Military Medical University in Shanghai and colleagues.
Additionally, “we found that comorbid [AFib] was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation. Moreover, comorbid [AFib] was associated with adverse clinical outcomes, including increased in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke,” the researchers wrote in the study published in the journal CHEST.
Patients included in the study were aged at least 18 years, were diagnosed with end-stage COPD and on home oxygen, and were hospitalized because of a COPD-related exacerbation. Based on 1,345,270 weighted hospital admissions of adults with end-stage COPD on home oxygen who met the inclusion criteria for the study, 18.2% (244,488 admissions) of patients had AFib, and the prevalence of AFib in COPD patients increased over time from 2003 (12.9%) to 2014 (21.3%; P less than .0001).
Patients with AFib, compared with patients without AFib, were older (75.5 years vs. 69.6 years; P less than .0001) and more likely to be male (50.7% vs. 59.1%; P less than .0001) and white (80.9% vs. 74.4%; P less than .0001). Patients with AFib also had higher stroke risk reflected in higher CHA2DS2-VASc scores (3.26 vs. 2.45; P less than .0001), and higher likelihood of in-hospital mortality and readmission reflected in Elixhauser scores greater than or equal to 4 (51.2% vs. 35.6%).
In addition, the prevalence of AFib increased with increasing income. Larger hospitals in terms of bed size, urban environment, and Medicare insurance status also were associated with a higher AFib prevalence.
AFib was associated with an increased cost of $1,415 and an increased length of stay of 0.6 days after adjustment for potential confounders. AFib also predicted risk for several adverse events, including stroke (odds ratio, 1.80; in-hospital death, [OR, 1.54]), invasive mechanical ventilation (OR, 1.37), sepsis (OR, 1.23), noninvasive mechanical ventilation (OR, 1.14), acute kidney injury (OR, 1.09), and acute respiratory failure (OR, 1.09).
The researchers noted the database could have potentially overinflated AFib prevalence, as they could not differentiate index admissions and readmissions. The database also does not contain information about secondary diagnoses codes present on admission, which could make it difficult to identify adverse events that occurred during hospitalization.
“Our findings should prompt further efforts to identify the reasons for increased [AFib] prevalence and provide better management strategies for end-stage COPD patients comorbid with [AFib],” the researchers concluded.
This study was funded by a grant from the Fourth Round of the Shanghai 3-year Action Plan on Public Health Discipline and Talent Program. The authors reported no relevant conflict of interest.
SOURCE: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.
FROM CHEST
Key clinical point: Comorbid atrial fibrillation was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation, and of adverse outcomes including in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke.
Major finding: The prevalence of atrial fibrillation with end-stage chronic obstructive pulmonary disease increased over time from 2003 (12.9%) to 2014 (21.3%). Study details: A retrospective analysis based on 1,345,270 weighted hospital admissions of adults with end-stage chronic obstructive pulmonary disease on home oxygen from the Nationwide Impatient Sample during 2003-2014.
Disclosures: The study was funded by a grant from the Fourth Round of the Shanghai 3-Year Action Plan on Public Health Discipline and Talent Program. The authors reported no conflicts of interest.
Source: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.