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Myocarditis shows causal role in frequent PVCs
BOSTON – About half of patients who present with a new onset of frequent premature ventricular contractions without obvious underlying heart disease had an underlying myocardial inflammation that was often responsive to immunosuppressive treatment, according to a single-center series of 107 patients.
“Early diagnosis and appropriate treatment with immunosuppressive therapy can significantly affect the clinical course,” although large-scale, multicenter, randomized trials must confirm this as an effective management approach, Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. He stressed that the anecdotal efficacy seen in this series with immunosuppressive therapy and selected use of ablation treatment for the premature ventricular contractions (PVCs) applies only to patients with new-onset PVCs that occur at a rate of at least 5,000 during 24 hours who also have myocardial inflammation identified by a PET scan showing increased fluorodeoxyglucose (FDG) uptake.
The apparent impact of immunosuppressive treatment was “profound,” Dr. Lakkireddy said. The treatment usually involved prednisone and, in many patients, a second immunosuppressant agent such as azathioprine, cyclophosphamide, or methotrexate. The results suggest “a unique opportunity to intervene early with immunosuppression to change the natural course of the disease. PVCs may be the earliest sign of a disease process” featuring myocardial inflammation.
The data came from the Myocarditis and Ventricular Arrhythmia (MAVERIC) registry that Dr. Lakkireddy and his associates started because “we began seeing patients referred for ablations without underlying heart disease who had suddenly presented with a lot of PVCs,” he recalled, an observation that led them to systematically study these patients in an “arduous” process that involved several tests. One hundred seven patients met the registry’s inclusion criteria for new onset of frequent PVCs without apparent underlying heart disease, and roughly half of these patients showed clear evidence of myocardial inflammation by FDG and PET imaging. “If the PET is negative, I don’t worry about myocarditis, “ Dr. Lakkireddy said.
The 55 patients with apparent myocarditis on PET imaging, out of the 107 patients examined generally, had lower left ventricular (LV) ejection fractions averaging 46%, compared with 51% among the patients without myocarditis The patients with myocarditis further subdivided into 27 with preserved LV function, with an average ejection fraction of 60%, and 28 with a reduced LV function, with an average ejection fraction of 40%. The researchers saw an optimal response to immunosuppressive therapy in 18 of the 23 patients (78%) with preserved ejection fractions who received this treatment and in 13 of the 24 patients (54%) with diminished LV ejection fractions who got immunosuppressive therapy.
Twenty-eight of the 55 patients with myocarditis on PET imaging underwent a right-sided biopsy during their work-up, and 13 of these 28 biopsies (46%) showed a lymphocytic infiltrate of a type often seen in patients with postviral myocarditis. Seven of the 28 biopsied patients (25%) had completely normal-appearing cardiac tissue.
Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehinger Ingelheim, Bristol-Myers Squibb, Estech, Janssen, Pfizer, SentreHeart, and St. Jude.
SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-02.
I was quite taken by this study, which produced results that raise shock and alarm. I believe that the clinical condition that this study highlights is a real biological phenomenon that affects patients who were not on my radar screen.
From now on, I will certainly be more alert for and concerned about patients whom I see with an abrupt onset of frequent premature ventricular contractions, especially those who also have a reduced left ventricular ejection fraction. However the potential need to use serial PET examinations to identify and then follow these patients also raises concern about the cumulative radiation exposure patients could receive from serial PET studies.
David J. Callans, MD , is professor of medicine and associate director of electrophysiology at the University of Pennsylvania in Philadelphia. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and St. Jude. He made these comments as designated discussant for the report.
I was quite taken by this study, which produced results that raise shock and alarm. I believe that the clinical condition that this study highlights is a real biological phenomenon that affects patients who were not on my radar screen.
From now on, I will certainly be more alert for and concerned about patients whom I see with an abrupt onset of frequent premature ventricular contractions, especially those who also have a reduced left ventricular ejection fraction. However the potential need to use serial PET examinations to identify and then follow these patients also raises concern about the cumulative radiation exposure patients could receive from serial PET studies.
David J. Callans, MD , is professor of medicine and associate director of electrophysiology at the University of Pennsylvania in Philadelphia. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and St. Jude. He made these comments as designated discussant for the report.
I was quite taken by this study, which produced results that raise shock and alarm. I believe that the clinical condition that this study highlights is a real biological phenomenon that affects patients who were not on my radar screen.
From now on, I will certainly be more alert for and concerned about patients whom I see with an abrupt onset of frequent premature ventricular contractions, especially those who also have a reduced left ventricular ejection fraction. However the potential need to use serial PET examinations to identify and then follow these patients also raises concern about the cumulative radiation exposure patients could receive from serial PET studies.
David J. Callans, MD , is professor of medicine and associate director of electrophysiology at the University of Pennsylvania in Philadelphia. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and St. Jude. He made these comments as designated discussant for the report.
BOSTON – About half of patients who present with a new onset of frequent premature ventricular contractions without obvious underlying heart disease had an underlying myocardial inflammation that was often responsive to immunosuppressive treatment, according to a single-center series of 107 patients.
“Early diagnosis and appropriate treatment with immunosuppressive therapy can significantly affect the clinical course,” although large-scale, multicenter, randomized trials must confirm this as an effective management approach, Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. He stressed that the anecdotal efficacy seen in this series with immunosuppressive therapy and selected use of ablation treatment for the premature ventricular contractions (PVCs) applies only to patients with new-onset PVCs that occur at a rate of at least 5,000 during 24 hours who also have myocardial inflammation identified by a PET scan showing increased fluorodeoxyglucose (FDG) uptake.
The apparent impact of immunosuppressive treatment was “profound,” Dr. Lakkireddy said. The treatment usually involved prednisone and, in many patients, a second immunosuppressant agent such as azathioprine, cyclophosphamide, or methotrexate. The results suggest “a unique opportunity to intervene early with immunosuppression to change the natural course of the disease. PVCs may be the earliest sign of a disease process” featuring myocardial inflammation.
The data came from the Myocarditis and Ventricular Arrhythmia (MAVERIC) registry that Dr. Lakkireddy and his associates started because “we began seeing patients referred for ablations without underlying heart disease who had suddenly presented with a lot of PVCs,” he recalled, an observation that led them to systematically study these patients in an “arduous” process that involved several tests. One hundred seven patients met the registry’s inclusion criteria for new onset of frequent PVCs without apparent underlying heart disease, and roughly half of these patients showed clear evidence of myocardial inflammation by FDG and PET imaging. “If the PET is negative, I don’t worry about myocarditis, “ Dr. Lakkireddy said.
The 55 patients with apparent myocarditis on PET imaging, out of the 107 patients examined generally, had lower left ventricular (LV) ejection fractions averaging 46%, compared with 51% among the patients without myocarditis The patients with myocarditis further subdivided into 27 with preserved LV function, with an average ejection fraction of 60%, and 28 with a reduced LV function, with an average ejection fraction of 40%. The researchers saw an optimal response to immunosuppressive therapy in 18 of the 23 patients (78%) with preserved ejection fractions who received this treatment and in 13 of the 24 patients (54%) with diminished LV ejection fractions who got immunosuppressive therapy.
Twenty-eight of the 55 patients with myocarditis on PET imaging underwent a right-sided biopsy during their work-up, and 13 of these 28 biopsies (46%) showed a lymphocytic infiltrate of a type often seen in patients with postviral myocarditis. Seven of the 28 biopsied patients (25%) had completely normal-appearing cardiac tissue.
Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehinger Ingelheim, Bristol-Myers Squibb, Estech, Janssen, Pfizer, SentreHeart, and St. Jude.
SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-02.
BOSTON – About half of patients who present with a new onset of frequent premature ventricular contractions without obvious underlying heart disease had an underlying myocardial inflammation that was often responsive to immunosuppressive treatment, according to a single-center series of 107 patients.
“Early diagnosis and appropriate treatment with immunosuppressive therapy can significantly affect the clinical course,” although large-scale, multicenter, randomized trials must confirm this as an effective management approach, Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. He stressed that the anecdotal efficacy seen in this series with immunosuppressive therapy and selected use of ablation treatment for the premature ventricular contractions (PVCs) applies only to patients with new-onset PVCs that occur at a rate of at least 5,000 during 24 hours who also have myocardial inflammation identified by a PET scan showing increased fluorodeoxyglucose (FDG) uptake.
The apparent impact of immunosuppressive treatment was “profound,” Dr. Lakkireddy said. The treatment usually involved prednisone and, in many patients, a second immunosuppressant agent such as azathioprine, cyclophosphamide, or methotrexate. The results suggest “a unique opportunity to intervene early with immunosuppression to change the natural course of the disease. PVCs may be the earliest sign of a disease process” featuring myocardial inflammation.
The data came from the Myocarditis and Ventricular Arrhythmia (MAVERIC) registry that Dr. Lakkireddy and his associates started because “we began seeing patients referred for ablations without underlying heart disease who had suddenly presented with a lot of PVCs,” he recalled, an observation that led them to systematically study these patients in an “arduous” process that involved several tests. One hundred seven patients met the registry’s inclusion criteria for new onset of frequent PVCs without apparent underlying heart disease, and roughly half of these patients showed clear evidence of myocardial inflammation by FDG and PET imaging. “If the PET is negative, I don’t worry about myocarditis, “ Dr. Lakkireddy said.
The 55 patients with apparent myocarditis on PET imaging, out of the 107 patients examined generally, had lower left ventricular (LV) ejection fractions averaging 46%, compared with 51% among the patients without myocarditis The patients with myocarditis further subdivided into 27 with preserved LV function, with an average ejection fraction of 60%, and 28 with a reduced LV function, with an average ejection fraction of 40%. The researchers saw an optimal response to immunosuppressive therapy in 18 of the 23 patients (78%) with preserved ejection fractions who received this treatment and in 13 of the 24 patients (54%) with diminished LV ejection fractions who got immunosuppressive therapy.
Twenty-eight of the 55 patients with myocarditis on PET imaging underwent a right-sided biopsy during their work-up, and 13 of these 28 biopsies (46%) showed a lymphocytic infiltrate of a type often seen in patients with postviral myocarditis. Seven of the 28 biopsied patients (25%) had completely normal-appearing cardiac tissue.
Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehinger Ingelheim, Bristol-Myers Squibb, Estech, Janssen, Pfizer, SentreHeart, and St. Jude.
SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-02.
REPORTING FROM HEART RHYTHM 2018
Key clinical point:
Major finding: Immunosuppressive therapy resolved myocarditis in two-thirds of 51% of patients with new-onset, frequents PVCs.
Study details: Single-center series with 107 patients.
Disclosures: Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehinger Ingelheim, Bristol-Myers Squibb, Estech, Janssen, Pfizer, SentreHeart, and St. Jude.
Source: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-02.
A fib ablation in HFrEF patients gains momentum
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
EXPERT ANALYSIS FROM HEART RHYTHM 2018
FDA recalls HeartMate 3 LV assist device
The HeartMate 3 left ventricular assist device received a class 1 recall from the Food and Drug Administration on May 17, an action the agency publicly announced on May 22.
The FDA’s step formalized a “corrective action” that the HeartMate 3’s manufacturer, Abbott, first issued in early April and then announced in early May, which said the device used to treat patients with severe advanced heart failure was subject to “outflow graft twist occlusions” that trigger a persistent low-flow alarm and “can result in serious adverse events such as hemodynamic compromise, thrombus, and death,” according to the FDA’s May 17 statement.
The class 1 recall category the FDA applied means the agency rates the danger posed as a “situation where there is a reasonable chance that a product will cause serious health problems or death.” However, in its statements, the agency has not suggested removing a well-functioning device from patients, nor has the agency called for discontinuing new placements of the HeartMate 3. The FDA gave a full endorsement to the approach Abbott suggested in its April 5 “Dear Physician” letter and then followed with a second letter on May 21.
The first letter attributed development of these twists in the tube that directs blood out from the device to accumulated mechanical forces from heartbeats, respiration, and activity, and also provided some management guidance that Abbott then expanded in its second letter.
The FDA cited some of the key steps Abbott recommended clinicians take with patients who receive a HeartMate 3. This included regular surveillance with transthoracic echocardiography, although echo is not considered definitive for identifying a graft twist obstruction and hence other investigations may also be needed. If the low-flow alarm sounds, a CT scan is “urgently” needed – as long as it’s not contraindicated – to identify a possible outflow twist. Abbott noted that surgical intervention may be needed to correct a twist.
Researchers recently reported 2-year follow-up data from 257 patients in MOMENTUM 3, the randomized pivotal trial for the HeartMate 3 that compared this fully magnetically levitated centrifugal-flow pump to the prior-generation, axial-flow pump. The composite endpoint of freedom from death, stroke, or need for repeat surgery after 2 years was 80% in the HeartMate 3 recipients and 60% among patients in the control arm who received the older-model device (N Engl J Med. 2018 April 12; 378[15]:1386-95).
The HeartMate 3 left ventricular assist device received a class 1 recall from the Food and Drug Administration on May 17, an action the agency publicly announced on May 22.
The FDA’s step formalized a “corrective action” that the HeartMate 3’s manufacturer, Abbott, first issued in early April and then announced in early May, which said the device used to treat patients with severe advanced heart failure was subject to “outflow graft twist occlusions” that trigger a persistent low-flow alarm and “can result in serious adverse events such as hemodynamic compromise, thrombus, and death,” according to the FDA’s May 17 statement.
The class 1 recall category the FDA applied means the agency rates the danger posed as a “situation where there is a reasonable chance that a product will cause serious health problems or death.” However, in its statements, the agency has not suggested removing a well-functioning device from patients, nor has the agency called for discontinuing new placements of the HeartMate 3. The FDA gave a full endorsement to the approach Abbott suggested in its April 5 “Dear Physician” letter and then followed with a second letter on May 21.
The first letter attributed development of these twists in the tube that directs blood out from the device to accumulated mechanical forces from heartbeats, respiration, and activity, and also provided some management guidance that Abbott then expanded in its second letter.
The FDA cited some of the key steps Abbott recommended clinicians take with patients who receive a HeartMate 3. This included regular surveillance with transthoracic echocardiography, although echo is not considered definitive for identifying a graft twist obstruction and hence other investigations may also be needed. If the low-flow alarm sounds, a CT scan is “urgently” needed – as long as it’s not contraindicated – to identify a possible outflow twist. Abbott noted that surgical intervention may be needed to correct a twist.
Researchers recently reported 2-year follow-up data from 257 patients in MOMENTUM 3, the randomized pivotal trial for the HeartMate 3 that compared this fully magnetically levitated centrifugal-flow pump to the prior-generation, axial-flow pump. The composite endpoint of freedom from death, stroke, or need for repeat surgery after 2 years was 80% in the HeartMate 3 recipients and 60% among patients in the control arm who received the older-model device (N Engl J Med. 2018 April 12; 378[15]:1386-95).
The HeartMate 3 left ventricular assist device received a class 1 recall from the Food and Drug Administration on May 17, an action the agency publicly announced on May 22.
The FDA’s step formalized a “corrective action” that the HeartMate 3’s manufacturer, Abbott, first issued in early April and then announced in early May, which said the device used to treat patients with severe advanced heart failure was subject to “outflow graft twist occlusions” that trigger a persistent low-flow alarm and “can result in serious adverse events such as hemodynamic compromise, thrombus, and death,” according to the FDA’s May 17 statement.
The class 1 recall category the FDA applied means the agency rates the danger posed as a “situation where there is a reasonable chance that a product will cause serious health problems or death.” However, in its statements, the agency has not suggested removing a well-functioning device from patients, nor has the agency called for discontinuing new placements of the HeartMate 3. The FDA gave a full endorsement to the approach Abbott suggested in its April 5 “Dear Physician” letter and then followed with a second letter on May 21.
The first letter attributed development of these twists in the tube that directs blood out from the device to accumulated mechanical forces from heartbeats, respiration, and activity, and also provided some management guidance that Abbott then expanded in its second letter.
The FDA cited some of the key steps Abbott recommended clinicians take with patients who receive a HeartMate 3. This included regular surveillance with transthoracic echocardiography, although echo is not considered definitive for identifying a graft twist obstruction and hence other investigations may also be needed. If the low-flow alarm sounds, a CT scan is “urgently” needed – as long as it’s not contraindicated – to identify a possible outflow twist. Abbott noted that surgical intervention may be needed to correct a twist.
Researchers recently reported 2-year follow-up data from 257 patients in MOMENTUM 3, the randomized pivotal trial for the HeartMate 3 that compared this fully magnetically levitated centrifugal-flow pump to the prior-generation, axial-flow pump. The composite endpoint of freedom from death, stroke, or need for repeat surgery after 2 years was 80% in the HeartMate 3 recipients and 60% among patients in the control arm who received the older-model device (N Engl J Med. 2018 April 12; 378[15]:1386-95).
FDA approval expected for CCM in heart failure patients
BOSTON – Positive results from a confirmatory trial appear to put the Optimizer by Impulse Dynamics, a cardiac contractility modulation (CCM) device for patients with function-limiting heart failure, on track for imminent U.S. marketing approval by the Food and Drug Administration. If that happens, several hundreds of thousands of U.S. heart failure patients would immediately become candidates for this treatment based on the enrolled study populations, the benefits shown, and current treatment options for advanced heart failure, experts predicted.
CCM “promises to meet a very large unmet need in heart failure,” William T. Abraham, MD, said as he presented the confirmatory study’s results at the annual scientific sessions of the Heart Rhythm Society. ”These patients aren’t doing well, but don’t qualify” for a heart transplant, left ventricular assist device, implantable cardioverter defibrillator, or cardiac resynchronization therapy (CRT), noted Dr. Abraham, professor and director of cardiovascular medicine at the Ohio State University in Columbus. In the months following the anticipated FDA approval, Dr. Abraham said he expects the device will be implanted in tens of thousands of U.S. heart failure patients who match the criteria of those who got the biggest benefit from CCM.
“There are few if any evidence-based treatments for patients with an ejection fraction of 35%-45%. This is an underserved population, so the potential of CCM is appropriately high,” Dr. Abraham said.
Researchers designed the study in consultation with the FDA to resolve lingering regulatory concerns following completion of three prior randomized trials with a total of nearly 650 patients. Dr. Abraham simultaneously reported the results at the meeting and published them in a report (JACC Heart Failure. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010); these results from 160 patients – 74 of whom received the device and 86 of whom continued medical therapy – showed the superiority of the device for the primary endpoint of change in exercise capacity (as measured by peak oxygen uptake) and for the secondary endpoints of quality of life (as measured with the Minnesota Living With Heart Failure Questionnaire) and functional status (as measured by New York Heart Association class). The boost in exercise capacity, an average increase of 0.84 ml/kg per min in peak oxygen uptake after 24 weeks, “was similar to the improvement seen with CRT in patients with a wide QRS interval” who thereby qualified for CRT placement, Dr. Abraham said.
The CCM device also met the study’s prespecified safety endpoint of a complication rate of less than 30% – with an actual rate of 10%. “The complications were those we expect from implanted leads and pulse generators and were comparable to what happens with other implanted rhythm devices. In the context of the benefits patients received and their having no other treatment options, I see the complication rate as acceptable,” Dr. Abraham said during his report.
In summing up the trial’s results, Dr. Stevenson noted that “the safety endpoint was met, the primary endpoint and other functional endpoints were met, and functional endpoints are of vital importance to patients. The CCM story is not yet the CRT story,” with CRT having produced even larger effects in its pivotal trial, also led by Dr. Abraham (New Engl J Med. 2002 June 13;346[24]:1845-53), cautioned Dr. Stevenson. But in general she put a positive spin on the CCM device, saying that it “has ingenuity and innovation, and we look forward to a better understanding of which patients benefit from CCM and what we can tell them about the magnitude and duration of the benefit.”
The FIX-HF-5C trial was sponsored by Impulse Dynamics, the company developing the CCM Optimizer device. Dr. Abraham has been a consultant to Impulse Dynamics, as well as to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical. Dr. Singh has been a consultant to Biotronik, Boston Scientific, Liva Nova, Medtronic, and St. Jude. Dr. Stevenson has received research funding from Abbott and Novartis. Dr. Yancy had no disclosures.
SOURCE: Abraham W et al. Heart Rhythm 2018, Abstract B-LBCT01-02.
BOSTON – Positive results from a confirmatory trial appear to put the Optimizer by Impulse Dynamics, a cardiac contractility modulation (CCM) device for patients with function-limiting heart failure, on track for imminent U.S. marketing approval by the Food and Drug Administration. If that happens, several hundreds of thousands of U.S. heart failure patients would immediately become candidates for this treatment based on the enrolled study populations, the benefits shown, and current treatment options for advanced heart failure, experts predicted.
CCM “promises to meet a very large unmet need in heart failure,” William T. Abraham, MD, said as he presented the confirmatory study’s results at the annual scientific sessions of the Heart Rhythm Society. ”These patients aren’t doing well, but don’t qualify” for a heart transplant, left ventricular assist device, implantable cardioverter defibrillator, or cardiac resynchronization therapy (CRT), noted Dr. Abraham, professor and director of cardiovascular medicine at the Ohio State University in Columbus. In the months following the anticipated FDA approval, Dr. Abraham said he expects the device will be implanted in tens of thousands of U.S. heart failure patients who match the criteria of those who got the biggest benefit from CCM.
“There are few if any evidence-based treatments for patients with an ejection fraction of 35%-45%. This is an underserved population, so the potential of CCM is appropriately high,” Dr. Abraham said.
Researchers designed the study in consultation with the FDA to resolve lingering regulatory concerns following completion of three prior randomized trials with a total of nearly 650 patients. Dr. Abraham simultaneously reported the results at the meeting and published them in a report (JACC Heart Failure. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010); these results from 160 patients – 74 of whom received the device and 86 of whom continued medical therapy – showed the superiority of the device for the primary endpoint of change in exercise capacity (as measured by peak oxygen uptake) and for the secondary endpoints of quality of life (as measured with the Minnesota Living With Heart Failure Questionnaire) and functional status (as measured by New York Heart Association class). The boost in exercise capacity, an average increase of 0.84 ml/kg per min in peak oxygen uptake after 24 weeks, “was similar to the improvement seen with CRT in patients with a wide QRS interval” who thereby qualified for CRT placement, Dr. Abraham said.
The CCM device also met the study’s prespecified safety endpoint of a complication rate of less than 30% – with an actual rate of 10%. “The complications were those we expect from implanted leads and pulse generators and were comparable to what happens with other implanted rhythm devices. In the context of the benefits patients received and their having no other treatment options, I see the complication rate as acceptable,” Dr. Abraham said during his report.
In summing up the trial’s results, Dr. Stevenson noted that “the safety endpoint was met, the primary endpoint and other functional endpoints were met, and functional endpoints are of vital importance to patients. The CCM story is not yet the CRT story,” with CRT having produced even larger effects in its pivotal trial, also led by Dr. Abraham (New Engl J Med. 2002 June 13;346[24]:1845-53), cautioned Dr. Stevenson. But in general she put a positive spin on the CCM device, saying that it “has ingenuity and innovation, and we look forward to a better understanding of which patients benefit from CCM and what we can tell them about the magnitude and duration of the benefit.”
The FIX-HF-5C trial was sponsored by Impulse Dynamics, the company developing the CCM Optimizer device. Dr. Abraham has been a consultant to Impulse Dynamics, as well as to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical. Dr. Singh has been a consultant to Biotronik, Boston Scientific, Liva Nova, Medtronic, and St. Jude. Dr. Stevenson has received research funding from Abbott and Novartis. Dr. Yancy had no disclosures.
SOURCE: Abraham W et al. Heart Rhythm 2018, Abstract B-LBCT01-02.
BOSTON – Positive results from a confirmatory trial appear to put the Optimizer by Impulse Dynamics, a cardiac contractility modulation (CCM) device for patients with function-limiting heart failure, on track for imminent U.S. marketing approval by the Food and Drug Administration. If that happens, several hundreds of thousands of U.S. heart failure patients would immediately become candidates for this treatment based on the enrolled study populations, the benefits shown, and current treatment options for advanced heart failure, experts predicted.
CCM “promises to meet a very large unmet need in heart failure,” William T. Abraham, MD, said as he presented the confirmatory study’s results at the annual scientific sessions of the Heart Rhythm Society. ”These patients aren’t doing well, but don’t qualify” for a heart transplant, left ventricular assist device, implantable cardioverter defibrillator, or cardiac resynchronization therapy (CRT), noted Dr. Abraham, professor and director of cardiovascular medicine at the Ohio State University in Columbus. In the months following the anticipated FDA approval, Dr. Abraham said he expects the device will be implanted in tens of thousands of U.S. heart failure patients who match the criteria of those who got the biggest benefit from CCM.
“There are few if any evidence-based treatments for patients with an ejection fraction of 35%-45%. This is an underserved population, so the potential of CCM is appropriately high,” Dr. Abraham said.
Researchers designed the study in consultation with the FDA to resolve lingering regulatory concerns following completion of three prior randomized trials with a total of nearly 650 patients. Dr. Abraham simultaneously reported the results at the meeting and published them in a report (JACC Heart Failure. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010); these results from 160 patients – 74 of whom received the device and 86 of whom continued medical therapy – showed the superiority of the device for the primary endpoint of change in exercise capacity (as measured by peak oxygen uptake) and for the secondary endpoints of quality of life (as measured with the Minnesota Living With Heart Failure Questionnaire) and functional status (as measured by New York Heart Association class). The boost in exercise capacity, an average increase of 0.84 ml/kg per min in peak oxygen uptake after 24 weeks, “was similar to the improvement seen with CRT in patients with a wide QRS interval” who thereby qualified for CRT placement, Dr. Abraham said.
The CCM device also met the study’s prespecified safety endpoint of a complication rate of less than 30% – with an actual rate of 10%. “The complications were those we expect from implanted leads and pulse generators and were comparable to what happens with other implanted rhythm devices. In the context of the benefits patients received and their having no other treatment options, I see the complication rate as acceptable,” Dr. Abraham said during his report.
In summing up the trial’s results, Dr. Stevenson noted that “the safety endpoint was met, the primary endpoint and other functional endpoints were met, and functional endpoints are of vital importance to patients. The CCM story is not yet the CRT story,” with CRT having produced even larger effects in its pivotal trial, also led by Dr. Abraham (New Engl J Med. 2002 June 13;346[24]:1845-53), cautioned Dr. Stevenson. But in general she put a positive spin on the CCM device, saying that it “has ingenuity and innovation, and we look forward to a better understanding of which patients benefit from CCM and what we can tell them about the magnitude and duration of the benefit.”
The FIX-HF-5C trial was sponsored by Impulse Dynamics, the company developing the CCM Optimizer device. Dr. Abraham has been a consultant to Impulse Dynamics, as well as to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical. Dr. Singh has been a consultant to Biotronik, Boston Scientific, Liva Nova, Medtronic, and St. Jude. Dr. Stevenson has received research funding from Abbott and Novartis. Dr. Yancy had no disclosures.
SOURCE: Abraham W et al. Heart Rhythm 2018, Abstract B-LBCT01-02.
REPORTING FROM HEART RHYTHM 2018
Babies exposed to SSRIs in utero have decreased LV size
TORONTO – according to a small study presented at the Pediatric Academic Societies annual meeting.
“Given the frequency of SSRI use during pregnancy and continued conflicting results regarding cardiac effects, it is an important area of study,” senior author Sarah Haskell, DO, said in an interview. Her group at the University of Iowa in Coralville, which includes first author Deidra Ansah, MD, previously demonstrated reduced ventricular size and cardiac function in sertraline-exposed animal models.
Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular (RV) diameter in diastole (P = .02) and a 22% reduction in left ventricular (LV) volume in systole (P = .02). They also had decreased LV lengths in diastole and systole (P = .045 and .004, respectively), but no impact was noted on cardiac function, as measured by shortening fraction.
“While cardiac function was appropriate on the initial echocardiogram, there were significant differences in cardiac dimensions,” said Dr. Haskell. “Whether these differences influence health and disease susceptibility requires further, longer-term studies.”
Her group plans to continue investigating the effects of SSRIs on cardiac development and also plans to study the offspring of women who are depressed but not on pharmacologic treatment to determine the effects of depression alone on cardiac size and function.
Dr. Haskell and her colleagues studied 21 term infants without and 20 term infants with exposure to in utero SSRIs who underwent standard echocardiograms including four-chamber and M-mode views within 48 hours of life. Exclusion criteria included prematurity, large or small for gestational age, any respiratory or cardiac support, and any major congenital malformations.
The mothers of exposed infants had higher depression scores compared with controls (P = .004), and had minimal to mild depression. Otherwise, they were similar in terms of age, weight, and likelihood of having chronic or gestational hypertension or diabetes. There also were no differences in maternal conditions or infant birth weight, body surface area or gestational age.
In the infants, no differences were seen in the occurrence of patent foramen ovale, patent ductus arteriosus, ventricular septal defect, or peripheral pulmonary artery stenosis.
This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
TORONTO – according to a small study presented at the Pediatric Academic Societies annual meeting.
“Given the frequency of SSRI use during pregnancy and continued conflicting results regarding cardiac effects, it is an important area of study,” senior author Sarah Haskell, DO, said in an interview. Her group at the University of Iowa in Coralville, which includes first author Deidra Ansah, MD, previously demonstrated reduced ventricular size and cardiac function in sertraline-exposed animal models.
Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular (RV) diameter in diastole (P = .02) and a 22% reduction in left ventricular (LV) volume in systole (P = .02). They also had decreased LV lengths in diastole and systole (P = .045 and .004, respectively), but no impact was noted on cardiac function, as measured by shortening fraction.
“While cardiac function was appropriate on the initial echocardiogram, there were significant differences in cardiac dimensions,” said Dr. Haskell. “Whether these differences influence health and disease susceptibility requires further, longer-term studies.”
Her group plans to continue investigating the effects of SSRIs on cardiac development and also plans to study the offspring of women who are depressed but not on pharmacologic treatment to determine the effects of depression alone on cardiac size and function.
Dr. Haskell and her colleagues studied 21 term infants without and 20 term infants with exposure to in utero SSRIs who underwent standard echocardiograms including four-chamber and M-mode views within 48 hours of life. Exclusion criteria included prematurity, large or small for gestational age, any respiratory or cardiac support, and any major congenital malformations.
The mothers of exposed infants had higher depression scores compared with controls (P = .004), and had minimal to mild depression. Otherwise, they were similar in terms of age, weight, and likelihood of having chronic or gestational hypertension or diabetes. There also were no differences in maternal conditions or infant birth weight, body surface area or gestational age.
In the infants, no differences were seen in the occurrence of patent foramen ovale, patent ductus arteriosus, ventricular septal defect, or peripheral pulmonary artery stenosis.
This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
TORONTO – according to a small study presented at the Pediatric Academic Societies annual meeting.
“Given the frequency of SSRI use during pregnancy and continued conflicting results regarding cardiac effects, it is an important area of study,” senior author Sarah Haskell, DO, said in an interview. Her group at the University of Iowa in Coralville, which includes first author Deidra Ansah, MD, previously demonstrated reduced ventricular size and cardiac function in sertraline-exposed animal models.
Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular (RV) diameter in diastole (P = .02) and a 22% reduction in left ventricular (LV) volume in systole (P = .02). They also had decreased LV lengths in diastole and systole (P = .045 and .004, respectively), but no impact was noted on cardiac function, as measured by shortening fraction.
“While cardiac function was appropriate on the initial echocardiogram, there were significant differences in cardiac dimensions,” said Dr. Haskell. “Whether these differences influence health and disease susceptibility requires further, longer-term studies.”
Her group plans to continue investigating the effects of SSRIs on cardiac development and also plans to study the offspring of women who are depressed but not on pharmacologic treatment to determine the effects of depression alone on cardiac size and function.
Dr. Haskell and her colleagues studied 21 term infants without and 20 term infants with exposure to in utero SSRIs who underwent standard echocardiograms including four-chamber and M-mode views within 48 hours of life. Exclusion criteria included prematurity, large or small for gestational age, any respiratory or cardiac support, and any major congenital malformations.
The mothers of exposed infants had higher depression scores compared with controls (P = .004), and had minimal to mild depression. Otherwise, they were similar in terms of age, weight, and likelihood of having chronic or gestational hypertension or diabetes. There also were no differences in maternal conditions or infant birth weight, body surface area or gestational age.
In the infants, no differences were seen in the occurrence of patent foramen ovale, patent ductus arteriosus, ventricular septal defect, or peripheral pulmonary artery stenosis.
This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
AT PAS 2018
Key clinical point: Babies exposed to SSRIs in utero have smaller hearts compared with babies not exposed to SSRIs.
Major finding: Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular diameter in diastole (P = .02) and a 22% reduction in left ventricular volume in systole (P = .02).
Study details: A study of 20 babies exposed to SSRIs in utero and 21 not exposed.
Disclosures: This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
CABANA: AF ablation ties drug management, with an asterisk for crossovers
BOSTON – Results from the CABANA trial, the long-awaited, head-to-head comparison of percutaneous catheter ablation with drug therapy for the treatment of atrial fibrillation by restoring sinus rhythm, failed to accomplish what it was designed to prove.
That is, that catheter ablation was superior to medical management for a combined endpoint of all-cause death, stroke, serious bleeding, or cardiac arrest.
The trial results also gave proponents of catheter ablation some tantalizing hints that this approach actually may have been superior to antiarrhythmic drugs, if only the randomization assignments had been more closely followed as the trial proceeded. But that didn’t happen, with about 30% of patients assigned to medical management crossing over to undergo catheter ablation, presumably because they had received inadequate symptom relief from their drug regimens. In addition, 10% of patients assigned to catheter ablation didn’t undergo it, primarily because they reconsidered after randomization and decided to not choose the invasive option. These crossovers produced a disparity in the outcomes between the standard, intention-to-treat analysis, which showed a neutral difference between the two study arms, and the per-protocol analysis that censored out crossover patients. The per-protocol analysis showed a statistically significant, 27% relative risk reduction in the primary endpoint among the patients randomized to and actually treated with catheter ablation, compared with those randomized to and exclusively treated medically.
“A patient can’t receive benefit from ablation if you don’t ablate,” noted the study’s lead investigation, Douglas L. Packer, MD, as he reported the results at the annual scientific sessions of the Heart Rhythm Society. “When you have this many crossovers and so many patients not getting their assigned treatments, then an on-treatment analysis is required, said Dr. Packer, a cardiac electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.
The prespecified on-treatment analysis, which, instead of censoring crossover patients, analyzed outcomes based on the treatments that patients actually received, showed a statistically significant one-third reduction in the primary endpoint among the ablated patients and a statistically significant 40% relative reduction in all-cause mortality in the ablated arm, compared with those on medical management.
“For symptomatic treatment, and to restore and maintain sinus rhythm, there is no question that ablation is better. We knew that before this trial, and we know it even more convincingly now,” commented Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “To a large extent, we do ablations for symptomatic benefit; to get patients feeling better. And I think this trial will confirm that because this will likely follow the better reduction in atrial fibrillation burden, which was quite impressive in the study.” Dr. Packer said that the quality of life data collected in CABANA will come out in a report later in 2018.
The dilemma that Dr. Ruskin and other physicians who heard the results voiced was how best to interpret the study’s primary results.
“This trial was designed to address whether ablation has an impact [compared with medical management] on hard endpoints, like mortality, and the intention-to-treat analysis showed no difference. I feel bound to adhere to the intention-to-treat analysis, the primary result” the traditional default arbiter of a randomized trial’s outcome, Dr. Ruskin said in an interview, “But intention-to-treat analyses are built on a foundation where most patients are maintained on their assigned treatment.”
The results “tell us that there wasn’t harm from ablation,” Dr. Albert said during a press conference. “That is really important because, before this, we didn’t know for sure. These data make me a little more confident about offering patients ablation. I now have data to discuss with patients that’s useful for decision making.”
“There was certainly no signal whatsoever of harm by taking patients to ablation early” in their management, agreed Dr. Ruskin. “I find that very reassuring and encouraging.”
CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) started in 2009 and enrolled 2,204 patients with documented, new-onset paroxysmal or persistent atrial fibrillation (AF) at 110 centers in 10 countries. Patients averaged about 68 years of age, with about 15% at least 75 years old, and in general were what Dr. Packer characterized as a high-risk group, with a high prevalence of comorbidities: 23% with sleep apnea, 10% with cardiomyopathy, 15% with heart failure, 10% with a prior stroke or transient ischemic attack, and just over a third in a New York Heart Association functional class II or III. About 43% had paroxysmal AF, about 47% had persistent AF, and the remaining patients had long-standing persistent AF. The median duration of AF at the time of entry was just over 1 year.
The clinicians treating the patients assigned to medical management could decide on a case-by-case basis whether to use rate or rhythm control, and about 12% of patients received rate control. The trial design specified pulmonary-vein isolation as the method for left atrial ablation.
In the intention-to-treat analyses, ablation was linked to a 14% relative reduction in the composite primary endpoint, a nonsignificant difference. All-cause mortality was a relative 15% lower in the ablation arm, also not statistically significant. A third prespecified, secondary endpoint, all-cause mortality plus cardiovascular hospitalization, was 17% lower in the ablated patients than in those on drug treatment in the intention-to-treat analysis, a statistically significant difference (P = .002).
The adverse event rate in the ablation arm was “surprisingly” low, said Dr. Packer, with a 3.9% rate of complications from catheter insertion (more than half were hematomas), a 3.4% rate of complications from catheter manipulation within the heart (2.2% involved pericardial effusions that required no intervention), and a 1.8% rate of ablation-related events, most commonly severe pericardial chest pain. “The risks of ablation seem to be lower than we thought,” he said, but quickly added the caveat that all ablation operators in CABANA had to have performed at least 100 ablation cases prior to the trial. The observed safety applies to operators “who know what they’re doing,” he said. Adverse events in the medically treated patients were typical for patients treated with amiodarone, Dr. Packer said, with the most common events hyper- or hypothyroidism, in 1.6%, and an allergic reaction, in 0.6%. In the intention-to-treat analysis the incidence of recurrent AF following a 90-day blanking period after ablation was 47% lower in the ablated patients relative to the drug-treated patients (P less than .0001).
Dr. Packer also presented an intriguing subgroup analysis for the primary endpoint that showed ablation had the best performance relative to medical management in patients younger than 65 years, patients with a history of heart failure, minority patients, and those who entered the trial in NYHA functional class II or III. The subgroup analysis showed a signal for worse performance from ablation in patients who were at least 75 years old. “I’m concerned about these older patients; we need to look into this,” Dr. Packer said. He also expressed optimism that the good performance of ablation in heart failure patients, while an exploratory finding, suggested confirmation of the results reported recently from the CASTLE-AF trial, which also showed good outcomes from catheter ablation for treating patients with heart failure and AF (N Engl J Med. 2018 Feb 1;378[5]:417-27).
The main qualification Dr. Packer voiced about the CABANA results is that not every AF patient should get ablation. “All treatments are not right for all patients. Not everyone with AF needs ablation. You need to talk with patients about it.” But despite this caution, he declared that the results had already changed his practice.
“I much less often now say to patients ‘let’s go with a drug and see what happens.’ I’d still do that if I wasn’t sure that a patient’s symptoms were caused by their AF” as opposed to their underlying heart disease, but if I’m pretty certain that their symptoms are caused by their AF over the past few months, I’ve become more likely to say that front-line ablation is reasonable,” Dr. Packer said.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from all four of these companies and also from several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Albert has been a consultant to Myokardia and Sanofi Aventis and has received research funding from Roche Diagnostics and St. Jude.
SOURCE: Packer DL et al. HRS 2018, Abstract B-LBCT01-05.
The data from CABANA suggest that at the least, catheter ablation is the equivalent of drug therapy, and I think in many cases, it is probably superior. Patients with atrial fibrillation should be allowed to undergo ablation as their first treatment, performed by operators who know what they’re doing. These are excellent results, but they do not apply to every patient with atrial fibrillation; they apply to patients like those enrolled in the trial.
The results also speak very loudly about the importance of sinus rhythm in patients with heart failure. The results in the subgroup of patients with heart failure appear to support the findings from CASTLE-AF (N Engl J Med. 2018 Feb 1;378[5]:417-27).
Eric N. Prystowsky, MD , is a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis. He has been a consultant to CardioNet and Medtronic, has an equity interest in Stereotaxis, and receives fellowship support from Medtronic and St. Jude. He made these comments as designated discussant for CABANA.
The data from CABANA suggest that at the least, catheter ablation is the equivalent of drug therapy, and I think in many cases, it is probably superior. Patients with atrial fibrillation should be allowed to undergo ablation as their first treatment, performed by operators who know what they’re doing. These are excellent results, but they do not apply to every patient with atrial fibrillation; they apply to patients like those enrolled in the trial.
The results also speak very loudly about the importance of sinus rhythm in patients with heart failure. The results in the subgroup of patients with heart failure appear to support the findings from CASTLE-AF (N Engl J Med. 2018 Feb 1;378[5]:417-27).
Eric N. Prystowsky, MD , is a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis. He has been a consultant to CardioNet and Medtronic, has an equity interest in Stereotaxis, and receives fellowship support from Medtronic and St. Jude. He made these comments as designated discussant for CABANA.
The data from CABANA suggest that at the least, catheter ablation is the equivalent of drug therapy, and I think in many cases, it is probably superior. Patients with atrial fibrillation should be allowed to undergo ablation as their first treatment, performed by operators who know what they’re doing. These are excellent results, but they do not apply to every patient with atrial fibrillation; they apply to patients like those enrolled in the trial.
The results also speak very loudly about the importance of sinus rhythm in patients with heart failure. The results in the subgroup of patients with heart failure appear to support the findings from CASTLE-AF (N Engl J Med. 2018 Feb 1;378[5]:417-27).
Eric N. Prystowsky, MD , is a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis. He has been a consultant to CardioNet and Medtronic, has an equity interest in Stereotaxis, and receives fellowship support from Medtronic and St. Jude. He made these comments as designated discussant for CABANA.
BOSTON – Results from the CABANA trial, the long-awaited, head-to-head comparison of percutaneous catheter ablation with drug therapy for the treatment of atrial fibrillation by restoring sinus rhythm, failed to accomplish what it was designed to prove.
That is, that catheter ablation was superior to medical management for a combined endpoint of all-cause death, stroke, serious bleeding, or cardiac arrest.
The trial results also gave proponents of catheter ablation some tantalizing hints that this approach actually may have been superior to antiarrhythmic drugs, if only the randomization assignments had been more closely followed as the trial proceeded. But that didn’t happen, with about 30% of patients assigned to medical management crossing over to undergo catheter ablation, presumably because they had received inadequate symptom relief from their drug regimens. In addition, 10% of patients assigned to catheter ablation didn’t undergo it, primarily because they reconsidered after randomization and decided to not choose the invasive option. These crossovers produced a disparity in the outcomes between the standard, intention-to-treat analysis, which showed a neutral difference between the two study arms, and the per-protocol analysis that censored out crossover patients. The per-protocol analysis showed a statistically significant, 27% relative risk reduction in the primary endpoint among the patients randomized to and actually treated with catheter ablation, compared with those randomized to and exclusively treated medically.
“A patient can’t receive benefit from ablation if you don’t ablate,” noted the study’s lead investigation, Douglas L. Packer, MD, as he reported the results at the annual scientific sessions of the Heart Rhythm Society. “When you have this many crossovers and so many patients not getting their assigned treatments, then an on-treatment analysis is required, said Dr. Packer, a cardiac electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.
The prespecified on-treatment analysis, which, instead of censoring crossover patients, analyzed outcomes based on the treatments that patients actually received, showed a statistically significant one-third reduction in the primary endpoint among the ablated patients and a statistically significant 40% relative reduction in all-cause mortality in the ablated arm, compared with those on medical management.
“For symptomatic treatment, and to restore and maintain sinus rhythm, there is no question that ablation is better. We knew that before this trial, and we know it even more convincingly now,” commented Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “To a large extent, we do ablations for symptomatic benefit; to get patients feeling better. And I think this trial will confirm that because this will likely follow the better reduction in atrial fibrillation burden, which was quite impressive in the study.” Dr. Packer said that the quality of life data collected in CABANA will come out in a report later in 2018.
The dilemma that Dr. Ruskin and other physicians who heard the results voiced was how best to interpret the study’s primary results.
“This trial was designed to address whether ablation has an impact [compared with medical management] on hard endpoints, like mortality, and the intention-to-treat analysis showed no difference. I feel bound to adhere to the intention-to-treat analysis, the primary result” the traditional default arbiter of a randomized trial’s outcome, Dr. Ruskin said in an interview, “But intention-to-treat analyses are built on a foundation where most patients are maintained on their assigned treatment.”
The results “tell us that there wasn’t harm from ablation,” Dr. Albert said during a press conference. “That is really important because, before this, we didn’t know for sure. These data make me a little more confident about offering patients ablation. I now have data to discuss with patients that’s useful for decision making.”
“There was certainly no signal whatsoever of harm by taking patients to ablation early” in their management, agreed Dr. Ruskin. “I find that very reassuring and encouraging.”
CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) started in 2009 and enrolled 2,204 patients with documented, new-onset paroxysmal or persistent atrial fibrillation (AF) at 110 centers in 10 countries. Patients averaged about 68 years of age, with about 15% at least 75 years old, and in general were what Dr. Packer characterized as a high-risk group, with a high prevalence of comorbidities: 23% with sleep apnea, 10% with cardiomyopathy, 15% with heart failure, 10% with a prior stroke or transient ischemic attack, and just over a third in a New York Heart Association functional class II or III. About 43% had paroxysmal AF, about 47% had persistent AF, and the remaining patients had long-standing persistent AF. The median duration of AF at the time of entry was just over 1 year.
The clinicians treating the patients assigned to medical management could decide on a case-by-case basis whether to use rate or rhythm control, and about 12% of patients received rate control. The trial design specified pulmonary-vein isolation as the method for left atrial ablation.
In the intention-to-treat analyses, ablation was linked to a 14% relative reduction in the composite primary endpoint, a nonsignificant difference. All-cause mortality was a relative 15% lower in the ablation arm, also not statistically significant. A third prespecified, secondary endpoint, all-cause mortality plus cardiovascular hospitalization, was 17% lower in the ablated patients than in those on drug treatment in the intention-to-treat analysis, a statistically significant difference (P = .002).
The adverse event rate in the ablation arm was “surprisingly” low, said Dr. Packer, with a 3.9% rate of complications from catheter insertion (more than half were hematomas), a 3.4% rate of complications from catheter manipulation within the heart (2.2% involved pericardial effusions that required no intervention), and a 1.8% rate of ablation-related events, most commonly severe pericardial chest pain. “The risks of ablation seem to be lower than we thought,” he said, but quickly added the caveat that all ablation operators in CABANA had to have performed at least 100 ablation cases prior to the trial. The observed safety applies to operators “who know what they’re doing,” he said. Adverse events in the medically treated patients were typical for patients treated with amiodarone, Dr. Packer said, with the most common events hyper- or hypothyroidism, in 1.6%, and an allergic reaction, in 0.6%. In the intention-to-treat analysis the incidence of recurrent AF following a 90-day blanking period after ablation was 47% lower in the ablated patients relative to the drug-treated patients (P less than .0001).
Dr. Packer also presented an intriguing subgroup analysis for the primary endpoint that showed ablation had the best performance relative to medical management in patients younger than 65 years, patients with a history of heart failure, minority patients, and those who entered the trial in NYHA functional class II or III. The subgroup analysis showed a signal for worse performance from ablation in patients who were at least 75 years old. “I’m concerned about these older patients; we need to look into this,” Dr. Packer said. He also expressed optimism that the good performance of ablation in heart failure patients, while an exploratory finding, suggested confirmation of the results reported recently from the CASTLE-AF trial, which also showed good outcomes from catheter ablation for treating patients with heart failure and AF (N Engl J Med. 2018 Feb 1;378[5]:417-27).
The main qualification Dr. Packer voiced about the CABANA results is that not every AF patient should get ablation. “All treatments are not right for all patients. Not everyone with AF needs ablation. You need to talk with patients about it.” But despite this caution, he declared that the results had already changed his practice.
“I much less often now say to patients ‘let’s go with a drug and see what happens.’ I’d still do that if I wasn’t sure that a patient’s symptoms were caused by their AF” as opposed to their underlying heart disease, but if I’m pretty certain that their symptoms are caused by their AF over the past few months, I’ve become more likely to say that front-line ablation is reasonable,” Dr. Packer said.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from all four of these companies and also from several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Albert has been a consultant to Myokardia and Sanofi Aventis and has received research funding from Roche Diagnostics and St. Jude.
SOURCE: Packer DL et al. HRS 2018, Abstract B-LBCT01-05.
BOSTON – Results from the CABANA trial, the long-awaited, head-to-head comparison of percutaneous catheter ablation with drug therapy for the treatment of atrial fibrillation by restoring sinus rhythm, failed to accomplish what it was designed to prove.
That is, that catheter ablation was superior to medical management for a combined endpoint of all-cause death, stroke, serious bleeding, or cardiac arrest.
The trial results also gave proponents of catheter ablation some tantalizing hints that this approach actually may have been superior to antiarrhythmic drugs, if only the randomization assignments had been more closely followed as the trial proceeded. But that didn’t happen, with about 30% of patients assigned to medical management crossing over to undergo catheter ablation, presumably because they had received inadequate symptom relief from their drug regimens. In addition, 10% of patients assigned to catheter ablation didn’t undergo it, primarily because they reconsidered after randomization and decided to not choose the invasive option. These crossovers produced a disparity in the outcomes between the standard, intention-to-treat analysis, which showed a neutral difference between the two study arms, and the per-protocol analysis that censored out crossover patients. The per-protocol analysis showed a statistically significant, 27% relative risk reduction in the primary endpoint among the patients randomized to and actually treated with catheter ablation, compared with those randomized to and exclusively treated medically.
“A patient can’t receive benefit from ablation if you don’t ablate,” noted the study’s lead investigation, Douglas L. Packer, MD, as he reported the results at the annual scientific sessions of the Heart Rhythm Society. “When you have this many crossovers and so many patients not getting their assigned treatments, then an on-treatment analysis is required, said Dr. Packer, a cardiac electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.
The prespecified on-treatment analysis, which, instead of censoring crossover patients, analyzed outcomes based on the treatments that patients actually received, showed a statistically significant one-third reduction in the primary endpoint among the ablated patients and a statistically significant 40% relative reduction in all-cause mortality in the ablated arm, compared with those on medical management.
“For symptomatic treatment, and to restore and maintain sinus rhythm, there is no question that ablation is better. We knew that before this trial, and we know it even more convincingly now,” commented Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “To a large extent, we do ablations for symptomatic benefit; to get patients feeling better. And I think this trial will confirm that because this will likely follow the better reduction in atrial fibrillation burden, which was quite impressive in the study.” Dr. Packer said that the quality of life data collected in CABANA will come out in a report later in 2018.
The dilemma that Dr. Ruskin and other physicians who heard the results voiced was how best to interpret the study’s primary results.
“This trial was designed to address whether ablation has an impact [compared with medical management] on hard endpoints, like mortality, and the intention-to-treat analysis showed no difference. I feel bound to adhere to the intention-to-treat analysis, the primary result” the traditional default arbiter of a randomized trial’s outcome, Dr. Ruskin said in an interview, “But intention-to-treat analyses are built on a foundation where most patients are maintained on their assigned treatment.”
The results “tell us that there wasn’t harm from ablation,” Dr. Albert said during a press conference. “That is really important because, before this, we didn’t know for sure. These data make me a little more confident about offering patients ablation. I now have data to discuss with patients that’s useful for decision making.”
“There was certainly no signal whatsoever of harm by taking patients to ablation early” in their management, agreed Dr. Ruskin. “I find that very reassuring and encouraging.”
CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) started in 2009 and enrolled 2,204 patients with documented, new-onset paroxysmal or persistent atrial fibrillation (AF) at 110 centers in 10 countries. Patients averaged about 68 years of age, with about 15% at least 75 years old, and in general were what Dr. Packer characterized as a high-risk group, with a high prevalence of comorbidities: 23% with sleep apnea, 10% with cardiomyopathy, 15% with heart failure, 10% with a prior stroke or transient ischemic attack, and just over a third in a New York Heart Association functional class II or III. About 43% had paroxysmal AF, about 47% had persistent AF, and the remaining patients had long-standing persistent AF. The median duration of AF at the time of entry was just over 1 year.
The clinicians treating the patients assigned to medical management could decide on a case-by-case basis whether to use rate or rhythm control, and about 12% of patients received rate control. The trial design specified pulmonary-vein isolation as the method for left atrial ablation.
In the intention-to-treat analyses, ablation was linked to a 14% relative reduction in the composite primary endpoint, a nonsignificant difference. All-cause mortality was a relative 15% lower in the ablation arm, also not statistically significant. A third prespecified, secondary endpoint, all-cause mortality plus cardiovascular hospitalization, was 17% lower in the ablated patients than in those on drug treatment in the intention-to-treat analysis, a statistically significant difference (P = .002).
The adverse event rate in the ablation arm was “surprisingly” low, said Dr. Packer, with a 3.9% rate of complications from catheter insertion (more than half were hematomas), a 3.4% rate of complications from catheter manipulation within the heart (2.2% involved pericardial effusions that required no intervention), and a 1.8% rate of ablation-related events, most commonly severe pericardial chest pain. “The risks of ablation seem to be lower than we thought,” he said, but quickly added the caveat that all ablation operators in CABANA had to have performed at least 100 ablation cases prior to the trial. The observed safety applies to operators “who know what they’re doing,” he said. Adverse events in the medically treated patients were typical for patients treated with amiodarone, Dr. Packer said, with the most common events hyper- or hypothyroidism, in 1.6%, and an allergic reaction, in 0.6%. In the intention-to-treat analysis the incidence of recurrent AF following a 90-day blanking period after ablation was 47% lower in the ablated patients relative to the drug-treated patients (P less than .0001).
Dr. Packer also presented an intriguing subgroup analysis for the primary endpoint that showed ablation had the best performance relative to medical management in patients younger than 65 years, patients with a history of heart failure, minority patients, and those who entered the trial in NYHA functional class II or III. The subgroup analysis showed a signal for worse performance from ablation in patients who were at least 75 years old. “I’m concerned about these older patients; we need to look into this,” Dr. Packer said. He also expressed optimism that the good performance of ablation in heart failure patients, while an exploratory finding, suggested confirmation of the results reported recently from the CASTLE-AF trial, which also showed good outcomes from catheter ablation for treating patients with heart failure and AF (N Engl J Med. 2018 Feb 1;378[5]:417-27).
The main qualification Dr. Packer voiced about the CABANA results is that not every AF patient should get ablation. “All treatments are not right for all patients. Not everyone with AF needs ablation. You need to talk with patients about it.” But despite this caution, he declared that the results had already changed his practice.
“I much less often now say to patients ‘let’s go with a drug and see what happens.’ I’d still do that if I wasn’t sure that a patient’s symptoms were caused by their AF” as opposed to their underlying heart disease, but if I’m pretty certain that their symptoms are caused by their AF over the past few months, I’ve become more likely to say that front-line ablation is reasonable,” Dr. Packer said.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from all four of these companies and also from several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Albert has been a consultant to Myokardia and Sanofi Aventis and has received research funding from Roche Diagnostics and St. Jude.
SOURCE: Packer DL et al. HRS 2018, Abstract B-LBCT01-05.
REPORTING FROM HEART RHYTHM 2018
Key clinical point: Catheter atrial fib ablation showed no significant benefit over medical management for the CABANA’s primary endpoint.
Major finding: The composite endpoint that included all-cause death was a nonsignificant 14% lower with ablation than with medical management in the intention-to-treat analysis.
Study details: CABANA, a multicenter, randomized trial with 2,204 patients.
Disclosures: CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from all four of these companies and from several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Albert has been a consultant to Myokardia and Sanofi-Aventis and has received research funding from Roche Diagnostics and St. Jude.
Source: Packer D et al. HRS 2018, Abstract B-LBCT01-05.
Implanted pulse generator ups exercise tolerance in HF
BOSTON – Cardiac contractility modulation (CCM), an electrical device–based modality, may improve exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%, results of a randomized, controlled trial suggested.
Notably, clinical effectiveness appeared to be even greater in the subset of patient with ejection fractions between 35% and 45%, according to results presented at the annual scientific sessions of the Heart Rhythm Society.
The CCM approach was designed to treat chronic heart failure patients with reduced and midrange ejection fractions. It involves the delivery of electrical signals during the cardiac absolute refractory period to enhance contraction strength. Key components include an atrial lead used for sensing and two ventricular leads used for sensing local electrical activity and delivery of CCM signals.
The device was previously evaluated in FIX-HF-5, a 428-patient randomized trial of CCM in patients with New York Heart Association functional class III/IV and reduced ejection fraction. That study failed to meet its primary efficacy end point, but a subgroup analysis showed significant treatment effects in patients with ejection fractions between 25% and 45%.
Consequently, Dr. Abraham initiated the FIX-HF-5 confirmatory study (FIX-HF-5C) to prospectively evaluate CCM in patients with ejection fractions in that range.
The study included 160 with NYHA class III/IV heart failure, QRS duration less than 130 ms, and ejection fractions of 25%-45% who were randomized either to CCM or to continued optimal medical therapy. The control arm included 86 patients, and the CCM arm included 74 patients, of whom 68 received device implantation.
For evaluating peak VO2, the primary end point of this confirmatory study, investigators used a Bayesian model that allowed them incorporate some data from the corresponding subgroup of patients with ejection fractions between 25% and 45% in the previous FIX-HF-5 randomized trial.
Using this model, they found the mean difference between CCM and medical therapy groups at week 24 was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552). The probability of CCM treatment’s superiority to control was 0.989, according to investigators, which exceeded the 0.975 threshold for statistical significance.
Dr. Abraham and his coinvestigators found that CCM implantation was safe, with a 90% complication-free rate, and that it improved both quality of life and functional status.
All efficacy endpoints were better in patients with ejection fractions of 35% or greater, confirming the subgroup analysis findings of the previous randomized trial, according to Dr. Abraham and his coinvestigators.
Survival free of cardiac death and heart failure hospitalization at 24 weeks was 97.1% in the CCM arm versus 89.2% in controls, which was a secondary finding that reached statistical significance in favor of CCM (P = .048) in one analysis of Kaplan-Meier estimates, investigators said in their report.
The CCM device could fulfill an unmet need for patients who have persistent heart failure despite optimal, guideline-based medical therapy, according to the investigators.
“Although ICDs are applicable to the broad population of patients with ejection fraction [at least] 35%, they do not deliver a therapy for improving exercise tolerance or quality of life,” they said in their report.
Research grant support for the study came from Impulse Dynamics. Dr. Abraham and several coauthors reported serving as consultants to the company.
SOURCE: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
BOSTON – Cardiac contractility modulation (CCM), an electrical device–based modality, may improve exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%, results of a randomized, controlled trial suggested.
Notably, clinical effectiveness appeared to be even greater in the subset of patient with ejection fractions between 35% and 45%, according to results presented at the annual scientific sessions of the Heart Rhythm Society.
The CCM approach was designed to treat chronic heart failure patients with reduced and midrange ejection fractions. It involves the delivery of electrical signals during the cardiac absolute refractory period to enhance contraction strength. Key components include an atrial lead used for sensing and two ventricular leads used for sensing local electrical activity and delivery of CCM signals.
The device was previously evaluated in FIX-HF-5, a 428-patient randomized trial of CCM in patients with New York Heart Association functional class III/IV and reduced ejection fraction. That study failed to meet its primary efficacy end point, but a subgroup analysis showed significant treatment effects in patients with ejection fractions between 25% and 45%.
Consequently, Dr. Abraham initiated the FIX-HF-5 confirmatory study (FIX-HF-5C) to prospectively evaluate CCM in patients with ejection fractions in that range.
The study included 160 with NYHA class III/IV heart failure, QRS duration less than 130 ms, and ejection fractions of 25%-45% who were randomized either to CCM or to continued optimal medical therapy. The control arm included 86 patients, and the CCM arm included 74 patients, of whom 68 received device implantation.
For evaluating peak VO2, the primary end point of this confirmatory study, investigators used a Bayesian model that allowed them incorporate some data from the corresponding subgroup of patients with ejection fractions between 25% and 45% in the previous FIX-HF-5 randomized trial.
Using this model, they found the mean difference between CCM and medical therapy groups at week 24 was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552). The probability of CCM treatment’s superiority to control was 0.989, according to investigators, which exceeded the 0.975 threshold for statistical significance.
Dr. Abraham and his coinvestigators found that CCM implantation was safe, with a 90% complication-free rate, and that it improved both quality of life and functional status.
All efficacy endpoints were better in patients with ejection fractions of 35% or greater, confirming the subgroup analysis findings of the previous randomized trial, according to Dr. Abraham and his coinvestigators.
Survival free of cardiac death and heart failure hospitalization at 24 weeks was 97.1% in the CCM arm versus 89.2% in controls, which was a secondary finding that reached statistical significance in favor of CCM (P = .048) in one analysis of Kaplan-Meier estimates, investigators said in their report.
The CCM device could fulfill an unmet need for patients who have persistent heart failure despite optimal, guideline-based medical therapy, according to the investigators.
“Although ICDs are applicable to the broad population of patients with ejection fraction [at least] 35%, they do not deliver a therapy for improving exercise tolerance or quality of life,” they said in their report.
Research grant support for the study came from Impulse Dynamics. Dr. Abraham and several coauthors reported serving as consultants to the company.
SOURCE: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
BOSTON – Cardiac contractility modulation (CCM), an electrical device–based modality, may improve exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%, results of a randomized, controlled trial suggested.
Notably, clinical effectiveness appeared to be even greater in the subset of patient with ejection fractions between 35% and 45%, according to results presented at the annual scientific sessions of the Heart Rhythm Society.
The CCM approach was designed to treat chronic heart failure patients with reduced and midrange ejection fractions. It involves the delivery of electrical signals during the cardiac absolute refractory period to enhance contraction strength. Key components include an atrial lead used for sensing and two ventricular leads used for sensing local electrical activity and delivery of CCM signals.
The device was previously evaluated in FIX-HF-5, a 428-patient randomized trial of CCM in patients with New York Heart Association functional class III/IV and reduced ejection fraction. That study failed to meet its primary efficacy end point, but a subgroup analysis showed significant treatment effects in patients with ejection fractions between 25% and 45%.
Consequently, Dr. Abraham initiated the FIX-HF-5 confirmatory study (FIX-HF-5C) to prospectively evaluate CCM in patients with ejection fractions in that range.
The study included 160 with NYHA class III/IV heart failure, QRS duration less than 130 ms, and ejection fractions of 25%-45% who were randomized either to CCM or to continued optimal medical therapy. The control arm included 86 patients, and the CCM arm included 74 patients, of whom 68 received device implantation.
For evaluating peak VO2, the primary end point of this confirmatory study, investigators used a Bayesian model that allowed them incorporate some data from the corresponding subgroup of patients with ejection fractions between 25% and 45% in the previous FIX-HF-5 randomized trial.
Using this model, they found the mean difference between CCM and medical therapy groups at week 24 was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552). The probability of CCM treatment’s superiority to control was 0.989, according to investigators, which exceeded the 0.975 threshold for statistical significance.
Dr. Abraham and his coinvestigators found that CCM implantation was safe, with a 90% complication-free rate, and that it improved both quality of life and functional status.
All efficacy endpoints were better in patients with ejection fractions of 35% or greater, confirming the subgroup analysis findings of the previous randomized trial, according to Dr. Abraham and his coinvestigators.
Survival free of cardiac death and heart failure hospitalization at 24 weeks was 97.1% in the CCM arm versus 89.2% in controls, which was a secondary finding that reached statistical significance in favor of CCM (P = .048) in one analysis of Kaplan-Meier estimates, investigators said in their report.
The CCM device could fulfill an unmet need for patients who have persistent heart failure despite optimal, guideline-based medical therapy, according to the investigators.
“Although ICDs are applicable to the broad population of patients with ejection fraction [at least] 35%, they do not deliver a therapy for improving exercise tolerance or quality of life,” they said in their report.
Research grant support for the study came from Impulse Dynamics. Dr. Abraham and several coauthors reported serving as consultants to the company.
SOURCE: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
REPORTING FROM HEART RHYTHM 2018
Key clinical point: Compared with continued medical therapy, cardiac contractility modulation (CCM) improved exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%.
Major finding: The difference in peak VO2 between study arms was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552).
Study details: A randomized controlled trial including 160 patients with NYHA class III/IV heart failure and ejection fraction between 25% and 45%.
Disclosures: Research grant support for the study came from Impulse Dynamics. Several study authors reported serving as consultants to Impulse Dynamics.
Source: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
Lower glucose target linked to improved mortality in critically ill
compared with patients with a target of 90-140 mg/dL, according to results of a retrospective cohort analysis.
With the computerized intravenous insulin protocol used in the study, the strict target could be achieved with a low rate of hypoglycemia, the authors wrote. The analysis was published in the journal CHEST®.
However, it does raise the possibility that earlier investigations finding an association between intensive insulin therapy and excess mortality “may have been accurate only in the setting of technologies which led to high rates of severe hypoglycemia,” they wrote.
The retrospective cohort analysis by Dr. Hersh and his colleagues included 1,809 adult patients treated at three different ICUs in two hospitals between January 2010 and December 2015. Treatment was delivered with a computerized ICU insulin infusion protocol that allows clinicians to choose between two blood glucose targets: 80-110 mg/dL or 90-140 mg/dL. The lower target was chosen for 951 patients, and the moderate target for 858 patients.
The most common primary admission diagnoses in the cohort included chest pain or acute coronary syndrome in 43.3%, cardiothoracic surgery in 31.9%, heart failure (including cardiogenic shock) in 6.8%, and vascular surgery in 6.0%.
While patients in the low blood glucose target group had a higher rate of moderate hypoglycemia, both groups had a low rate of severe hypoglycemia, at 1.16% in the low target group and 0.35% in the moderate target group (P = .051).
Unadjusted 30-day mortality was significantly lower in the 80-110–mg/dL group compared with the 90-140–mg/dL group (4.3% vs. 9.2%, respectively; P less than .001), according to the investigators.
Furthermore, logistic regression analysis showed that patients treated with a target of 80-110 mg/dL had a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL (odds ratio 0.65; 95% confidence interval, 0.43-0.98; P = .04).
These results advance the debate over appropriate blood glucose targets in critically ill patients, as they suggest that the effects of targeting blood glucose and the effects of severe hypoglycemia “can be separated,” the investigators wrote.
Current guidelines on intensive insulin therapy are based in part on findings of the NICE-SUGAR trial, which found that among adults treated in the ICU, intensive glucose control increased mortality. However, a post hoc analysis suggested the mortality increase in NICE-SUGAR was “largely driven by a significant incidence of moderate hypoglycemia, and to a greater degree severe hypoglycemia,” Dr. Hersh and his coauthors noted in their report.
“Given improvements in insulin delivery and glucose monitoring, a reassessment of potential benefits of [intensive insulin therapy] should once again be evaluated in a prospective randomized trial,” they wrote.
Dr. Hersh and his coauthors declared no financial or nonfinancial disclosures related to the study.
SOURCE: Hersh AM et al. CHEST 2018. doi: 10.1016/j.chest.2018.04.025.
compared with patients with a target of 90-140 mg/dL, according to results of a retrospective cohort analysis.
With the computerized intravenous insulin protocol used in the study, the strict target could be achieved with a low rate of hypoglycemia, the authors wrote. The analysis was published in the journal CHEST®.
However, it does raise the possibility that earlier investigations finding an association between intensive insulin therapy and excess mortality “may have been accurate only in the setting of technologies which led to high rates of severe hypoglycemia,” they wrote.
The retrospective cohort analysis by Dr. Hersh and his colleagues included 1,809 adult patients treated at three different ICUs in two hospitals between January 2010 and December 2015. Treatment was delivered with a computerized ICU insulin infusion protocol that allows clinicians to choose between two blood glucose targets: 80-110 mg/dL or 90-140 mg/dL. The lower target was chosen for 951 patients, and the moderate target for 858 patients.
The most common primary admission diagnoses in the cohort included chest pain or acute coronary syndrome in 43.3%, cardiothoracic surgery in 31.9%, heart failure (including cardiogenic shock) in 6.8%, and vascular surgery in 6.0%.
While patients in the low blood glucose target group had a higher rate of moderate hypoglycemia, both groups had a low rate of severe hypoglycemia, at 1.16% in the low target group and 0.35% in the moderate target group (P = .051).
Unadjusted 30-day mortality was significantly lower in the 80-110–mg/dL group compared with the 90-140–mg/dL group (4.3% vs. 9.2%, respectively; P less than .001), according to the investigators.
Furthermore, logistic regression analysis showed that patients treated with a target of 80-110 mg/dL had a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL (odds ratio 0.65; 95% confidence interval, 0.43-0.98; P = .04).
These results advance the debate over appropriate blood glucose targets in critically ill patients, as they suggest that the effects of targeting blood glucose and the effects of severe hypoglycemia “can be separated,” the investigators wrote.
Current guidelines on intensive insulin therapy are based in part on findings of the NICE-SUGAR trial, which found that among adults treated in the ICU, intensive glucose control increased mortality. However, a post hoc analysis suggested the mortality increase in NICE-SUGAR was “largely driven by a significant incidence of moderate hypoglycemia, and to a greater degree severe hypoglycemia,” Dr. Hersh and his coauthors noted in their report.
“Given improvements in insulin delivery and glucose monitoring, a reassessment of potential benefits of [intensive insulin therapy] should once again be evaluated in a prospective randomized trial,” they wrote.
Dr. Hersh and his coauthors declared no financial or nonfinancial disclosures related to the study.
SOURCE: Hersh AM et al. CHEST 2018. doi: 10.1016/j.chest.2018.04.025.
compared with patients with a target of 90-140 mg/dL, according to results of a retrospective cohort analysis.
With the computerized intravenous insulin protocol used in the study, the strict target could be achieved with a low rate of hypoglycemia, the authors wrote. The analysis was published in the journal CHEST®.
However, it does raise the possibility that earlier investigations finding an association between intensive insulin therapy and excess mortality “may have been accurate only in the setting of technologies which led to high rates of severe hypoglycemia,” they wrote.
The retrospective cohort analysis by Dr. Hersh and his colleagues included 1,809 adult patients treated at three different ICUs in two hospitals between January 2010 and December 2015. Treatment was delivered with a computerized ICU insulin infusion protocol that allows clinicians to choose between two blood glucose targets: 80-110 mg/dL or 90-140 mg/dL. The lower target was chosen for 951 patients, and the moderate target for 858 patients.
The most common primary admission diagnoses in the cohort included chest pain or acute coronary syndrome in 43.3%, cardiothoracic surgery in 31.9%, heart failure (including cardiogenic shock) in 6.8%, and vascular surgery in 6.0%.
While patients in the low blood glucose target group had a higher rate of moderate hypoglycemia, both groups had a low rate of severe hypoglycemia, at 1.16% in the low target group and 0.35% in the moderate target group (P = .051).
Unadjusted 30-day mortality was significantly lower in the 80-110–mg/dL group compared with the 90-140–mg/dL group (4.3% vs. 9.2%, respectively; P less than .001), according to the investigators.
Furthermore, logistic regression analysis showed that patients treated with a target of 80-110 mg/dL had a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL (odds ratio 0.65; 95% confidence interval, 0.43-0.98; P = .04).
These results advance the debate over appropriate blood glucose targets in critically ill patients, as they suggest that the effects of targeting blood glucose and the effects of severe hypoglycemia “can be separated,” the investigators wrote.
Current guidelines on intensive insulin therapy are based in part on findings of the NICE-SUGAR trial, which found that among adults treated in the ICU, intensive glucose control increased mortality. However, a post hoc analysis suggested the mortality increase in NICE-SUGAR was “largely driven by a significant incidence of moderate hypoglycemia, and to a greater degree severe hypoglycemia,” Dr. Hersh and his coauthors noted in their report.
“Given improvements in insulin delivery and glucose monitoring, a reassessment of potential benefits of [intensive insulin therapy] should once again be evaluated in a prospective randomized trial,” they wrote.
Dr. Hersh and his coauthors declared no financial or nonfinancial disclosures related to the study.
SOURCE: Hersh AM et al. CHEST 2018. doi: 10.1016/j.chest.2018.04.025.
FROM THE JOURNAL CHEST®
Key clinical point: Among critically ill cardiac and cardiothoracic patients, a lower glucose target was associated with improved 30-day mortality.
Major finding: Patients treated with a target of 80-110 mg/dL had a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL (odds ratio 0.65; 95% confidence interval, 0.43-0.98; P = .04).
Study details: A retrospective cohort analysis of 1,809 adult patients treated at three ICUs from two hospitals between January 2010 and December 2015.
Disclosures: The authors declared no disclosures.
Source: Hersh AM et al. CHEST 2018. doi: 10.1016/j.chest.2018.04.025.
Is medical aid in dying suicide?
WASHINGTON – Medical aid in dying is not the same as suicide; it is a way to give people with terminal illness and facing imminent death a way to die better and avoid the terrible, drawn-out deaths from chronic disease that often now occur, Margaret P. Battin, PhD, said at the annual conference of the American Association of Suicidology.
and is allowed now by law in Colorado, Hawaii, Montana, Oregon, Vermont, Washington, the District of Columbia, and by court decision in California. It’s also a legal option in Belgium, Canada, Luxembourg, the Netherlands, Switzerland, and parts of Germany, she said. Dr. Battin attributed the spread of legalized MAiD to the frequent terrible and protracted deaths people in industrialized countries face from chronic diseases such as cancer, heart disease, organ failure, dementia, stroke, and other neurologic disorders, and the comforting option of choice that MAiD offers these terminally ill patients. All the laws that have legalized MAiD draw distinctions between it and suicide, she noted.
“Even it the patient doesn’t act on this, someone facing death can find comfort knowing that if things get too bad, there is a way to avoid it, that they can have some control over their death. People want to remain in control, and this gives people a sense of control” that is not pathologic; it’s reassuring. “It can also make bereavement easier for others,” she said. Medical aid in dying “ helps people with terminal illness reduce their confusion, despair, and sense of impotence. When we can’t prevent death, this can make it better.” Dr. Battin also cited the restrictions these laws make to rule out people with mental illness or psychiatric problems that influence their choice of MAiD. That plus cultural and societal attitudes toward self-directed death mean that very few people actually wind up taking MAiD to completion.
But Thomas Joiner, PhD, dissented that the MAiD process successfully winnows out people who are acting on a desire for suicide in the traditional sense.
Another major problem with MAiD is that it focuses too much on self-determination and autonomy and downplays the importance of the social reverberations that this form of death has on others, he explained. “The social dimension is an afterthought [of MAiD], and that’s a problem.”
The American Association of Suicidality statement “has evolved, and Professor Battin had a lot to do with that, and I respect” the writing process. It shows better balance between autonomy and social connections, but I believe that [MAiD] is often an expression of [traditional] suicide,” Dr. Joiner said. MAiD has become more acceptable, “but that doesn’t make it right. It is trying to dodge the stigma of suicide.”
Dr. Battin and Dr. Joiner had no disclosures.
WASHINGTON – Medical aid in dying is not the same as suicide; it is a way to give people with terminal illness and facing imminent death a way to die better and avoid the terrible, drawn-out deaths from chronic disease that often now occur, Margaret P. Battin, PhD, said at the annual conference of the American Association of Suicidology.
and is allowed now by law in Colorado, Hawaii, Montana, Oregon, Vermont, Washington, the District of Columbia, and by court decision in California. It’s also a legal option in Belgium, Canada, Luxembourg, the Netherlands, Switzerland, and parts of Germany, she said. Dr. Battin attributed the spread of legalized MAiD to the frequent terrible and protracted deaths people in industrialized countries face from chronic diseases such as cancer, heart disease, organ failure, dementia, stroke, and other neurologic disorders, and the comforting option of choice that MAiD offers these terminally ill patients. All the laws that have legalized MAiD draw distinctions between it and suicide, she noted.
“Even it the patient doesn’t act on this, someone facing death can find comfort knowing that if things get too bad, there is a way to avoid it, that they can have some control over their death. People want to remain in control, and this gives people a sense of control” that is not pathologic; it’s reassuring. “It can also make bereavement easier for others,” she said. Medical aid in dying “ helps people with terminal illness reduce their confusion, despair, and sense of impotence. When we can’t prevent death, this can make it better.” Dr. Battin also cited the restrictions these laws make to rule out people with mental illness or psychiatric problems that influence their choice of MAiD. That plus cultural and societal attitudes toward self-directed death mean that very few people actually wind up taking MAiD to completion.
But Thomas Joiner, PhD, dissented that the MAiD process successfully winnows out people who are acting on a desire for suicide in the traditional sense.
Another major problem with MAiD is that it focuses too much on self-determination and autonomy and downplays the importance of the social reverberations that this form of death has on others, he explained. “The social dimension is an afterthought [of MAiD], and that’s a problem.”
The American Association of Suicidality statement “has evolved, and Professor Battin had a lot to do with that, and I respect” the writing process. It shows better balance between autonomy and social connections, but I believe that [MAiD] is often an expression of [traditional] suicide,” Dr. Joiner said. MAiD has become more acceptable, “but that doesn’t make it right. It is trying to dodge the stigma of suicide.”
Dr. Battin and Dr. Joiner had no disclosures.
WASHINGTON – Medical aid in dying is not the same as suicide; it is a way to give people with terminal illness and facing imminent death a way to die better and avoid the terrible, drawn-out deaths from chronic disease that often now occur, Margaret P. Battin, PhD, said at the annual conference of the American Association of Suicidology.
and is allowed now by law in Colorado, Hawaii, Montana, Oregon, Vermont, Washington, the District of Columbia, and by court decision in California. It’s also a legal option in Belgium, Canada, Luxembourg, the Netherlands, Switzerland, and parts of Germany, she said. Dr. Battin attributed the spread of legalized MAiD to the frequent terrible and protracted deaths people in industrialized countries face from chronic diseases such as cancer, heart disease, organ failure, dementia, stroke, and other neurologic disorders, and the comforting option of choice that MAiD offers these terminally ill patients. All the laws that have legalized MAiD draw distinctions between it and suicide, she noted.
“Even it the patient doesn’t act on this, someone facing death can find comfort knowing that if things get too bad, there is a way to avoid it, that they can have some control over their death. People want to remain in control, and this gives people a sense of control” that is not pathologic; it’s reassuring. “It can also make bereavement easier for others,” she said. Medical aid in dying “ helps people with terminal illness reduce their confusion, despair, and sense of impotence. When we can’t prevent death, this can make it better.” Dr. Battin also cited the restrictions these laws make to rule out people with mental illness or psychiatric problems that influence their choice of MAiD. That plus cultural and societal attitudes toward self-directed death mean that very few people actually wind up taking MAiD to completion.
But Thomas Joiner, PhD, dissented that the MAiD process successfully winnows out people who are acting on a desire for suicide in the traditional sense.
Another major problem with MAiD is that it focuses too much on self-determination and autonomy and downplays the importance of the social reverberations that this form of death has on others, he explained. “The social dimension is an afterthought [of MAiD], and that’s a problem.”
The American Association of Suicidality statement “has evolved, and Professor Battin had a lot to do with that, and I respect” the writing process. It shows better balance between autonomy and social connections, but I believe that [MAiD] is often an expression of [traditional] suicide,” Dr. Joiner said. MAiD has become more acceptable, “but that doesn’t make it right. It is trying to dodge the stigma of suicide.”
Dr. Battin and Dr. Joiner had no disclosures.
REPORTING FROM THE AAS ANNUAL CONFERENCE
MDedge Daily News: Can a nasal spray reverse suicidality?
Smoking boosts heart failure risk in black patients. Respiratory infections increase risk of heart attack and stroke. And pain relievers and inflammatory bowel disease? It’s complicated.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Smoking boosts heart failure risk in black patients. Respiratory infections increase risk of heart attack and stroke. And pain relievers and inflammatory bowel disease? It’s complicated.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Smoking boosts heart failure risk in black patients. Respiratory infections increase risk of heart attack and stroke. And pain relievers and inflammatory bowel disease? It’s complicated.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
