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New cryoablating catheter shows promising AF efficacy, safety
BOSTON – An ultra-low-temperature ablation catheter was safe and effective in the first 48 atrial fibrillation (AF) patients to undergo treatment with the device.
The ultra-low-temperature catheter, cooled by liquid nitrogen to –196° C, showed excellent safety and a high success rate, in the modest number of patients who have been followed for 6 or 12 months, Tom De Potter, MD, said at the annual International AF Symposium. The catheter is capable of delivering both focal and linear lesions, said Dr. De Potter, a cardiac electrophysiologist at the Cardiovascular Center of OLV Hospital in Aalst, Belgium.
He reported results on the first 48 AF patients treated with the catheter at either his center or at St. Antonius Hospital in Nieuwegein, the Netherlands, in the CryoCure2 (Investigation of the Adagio Cryoablation System in Patients With Atrial Fibrillation) study. The investigators included safety findings only from the first 13 patients treated, but they assessed both safety and efficacy for the following 35 patients.
The safety review showed one patient with a groin-puncture injury, and two patients with phrenic nerve palsy, but no cases of phrenic nerve palsy in the most recent 41 patients who were treated with an updated version of the catheter that included a cryomapping feature. None of the 48 patients had a stroke, transient ischemic attack, esophageal injury, tamponade, or MI.
The 35 patients reviewed for efficacy included 10 patients with paroxysmal AF and 25 with persistent AF. All five of the paroxysmal AF patients followed for at least 6 months, and all four of those patients followed for 12 months, showed no AF recurrences. One of the persistent AF patients never achieved cardioversion at the time of the ablation procedure. All 17 other persistent AF patients followed for at least 6 months remained in sinus rhythm at 6 months. Among the eight of these patients followed for at least 12 months after treatment, one patient had AF recurrence, so the current 12-month rate of freedom from recurrence is seven of nine patients (including the one who never achieved cardioversion), or 78%.
The average procedure time to perform pulmonary vein isolation (PVI) only was 106 minutes, and procedure time was 116 minutes in the patients who underwent PVI plus additional ablation procedures. Average ablation time was 12 minutes among those just having PVI, and 14 minutes in those who underwent PVI plus other ablations. The cryoablation catheter comes with 20 electrodes that allow it to also record electrograms.
The attraction of the ultra-low-temperature cryoablation catheter used in the study is it “can achieve complete PVI considerably faster” than other ablation methods while also achieving “unsurpassed efficacy,” Dr. De Potter said in a written statement. In addition, “the new, adjustable diagnostic capacity simplifies the procedure and makes it much less operator dependent,” he added.
BOSTON – An ultra-low-temperature ablation catheter was safe and effective in the first 48 atrial fibrillation (AF) patients to undergo treatment with the device.
The ultra-low-temperature catheter, cooled by liquid nitrogen to –196° C, showed excellent safety and a high success rate, in the modest number of patients who have been followed for 6 or 12 months, Tom De Potter, MD, said at the annual International AF Symposium. The catheter is capable of delivering both focal and linear lesions, said Dr. De Potter, a cardiac electrophysiologist at the Cardiovascular Center of OLV Hospital in Aalst, Belgium.
He reported results on the first 48 AF patients treated with the catheter at either his center or at St. Antonius Hospital in Nieuwegein, the Netherlands, in the CryoCure2 (Investigation of the Adagio Cryoablation System in Patients With Atrial Fibrillation) study. The investigators included safety findings only from the first 13 patients treated, but they assessed both safety and efficacy for the following 35 patients.
The safety review showed one patient with a groin-puncture injury, and two patients with phrenic nerve palsy, but no cases of phrenic nerve palsy in the most recent 41 patients who were treated with an updated version of the catheter that included a cryomapping feature. None of the 48 patients had a stroke, transient ischemic attack, esophageal injury, tamponade, or MI.
The 35 patients reviewed for efficacy included 10 patients with paroxysmal AF and 25 with persistent AF. All five of the paroxysmal AF patients followed for at least 6 months, and all four of those patients followed for 12 months, showed no AF recurrences. One of the persistent AF patients never achieved cardioversion at the time of the ablation procedure. All 17 other persistent AF patients followed for at least 6 months remained in sinus rhythm at 6 months. Among the eight of these patients followed for at least 12 months after treatment, one patient had AF recurrence, so the current 12-month rate of freedom from recurrence is seven of nine patients (including the one who never achieved cardioversion), or 78%.
The average procedure time to perform pulmonary vein isolation (PVI) only was 106 minutes, and procedure time was 116 minutes in the patients who underwent PVI plus additional ablation procedures. Average ablation time was 12 minutes among those just having PVI, and 14 minutes in those who underwent PVI plus other ablations. The cryoablation catheter comes with 20 electrodes that allow it to also record electrograms.
The attraction of the ultra-low-temperature cryoablation catheter used in the study is it “can achieve complete PVI considerably faster” than other ablation methods while also achieving “unsurpassed efficacy,” Dr. De Potter said in a written statement. In addition, “the new, adjustable diagnostic capacity simplifies the procedure and makes it much less operator dependent,” he added.
BOSTON – An ultra-low-temperature ablation catheter was safe and effective in the first 48 atrial fibrillation (AF) patients to undergo treatment with the device.
The ultra-low-temperature catheter, cooled by liquid nitrogen to –196° C, showed excellent safety and a high success rate, in the modest number of patients who have been followed for 6 or 12 months, Tom De Potter, MD, said at the annual International AF Symposium. The catheter is capable of delivering both focal and linear lesions, said Dr. De Potter, a cardiac electrophysiologist at the Cardiovascular Center of OLV Hospital in Aalst, Belgium.
He reported results on the first 48 AF patients treated with the catheter at either his center or at St. Antonius Hospital in Nieuwegein, the Netherlands, in the CryoCure2 (Investigation of the Adagio Cryoablation System in Patients With Atrial Fibrillation) study. The investigators included safety findings only from the first 13 patients treated, but they assessed both safety and efficacy for the following 35 patients.
The safety review showed one patient with a groin-puncture injury, and two patients with phrenic nerve palsy, but no cases of phrenic nerve palsy in the most recent 41 patients who were treated with an updated version of the catheter that included a cryomapping feature. None of the 48 patients had a stroke, transient ischemic attack, esophageal injury, tamponade, or MI.
The 35 patients reviewed for efficacy included 10 patients with paroxysmal AF and 25 with persistent AF. All five of the paroxysmal AF patients followed for at least 6 months, and all four of those patients followed for 12 months, showed no AF recurrences. One of the persistent AF patients never achieved cardioversion at the time of the ablation procedure. All 17 other persistent AF patients followed for at least 6 months remained in sinus rhythm at 6 months. Among the eight of these patients followed for at least 12 months after treatment, one patient had AF recurrence, so the current 12-month rate of freedom from recurrence is seven of nine patients (including the one who never achieved cardioversion), or 78%.
The average procedure time to perform pulmonary vein isolation (PVI) only was 106 minutes, and procedure time was 116 minutes in the patients who underwent PVI plus additional ablation procedures. Average ablation time was 12 minutes among those just having PVI, and 14 minutes in those who underwent PVI plus other ablations. The cryoablation catheter comes with 20 electrodes that allow it to also record electrograms.
The attraction of the ultra-low-temperature cryoablation catheter used in the study is it “can achieve complete PVI considerably faster” than other ablation methods while also achieving “unsurpassed efficacy,” Dr. De Potter said in a written statement. In addition, “the new, adjustable diagnostic capacity simplifies the procedure and makes it much less operator dependent,” he added.
REPORTING FROM THE AF SYMPOSIUM 2019
Key clinical point:
Major finding: A year after cryoablation, seven of nine treated patients with persistent atrial fibrillation remained recurrence free.
Study details: CryoCure2, a single arm, multicenter, European study with 48 patients.
Disclosures: The CryoCure2 study is sponsored by Adagio Medical, the company developing the cryoablation catheter. Dr. De Potter has received travel support from Adagio, and he has received research funding from Boston Scientific and Johnson & Johnson.
Medical advice prompts unneeded emergency visits by AF patients
BOSTON – Patients with atrial fibrillation who present to emergency departments, despite being asymptomatic, often go based on of their understanding of advice they had previously received from their physicians, according to results from a prospective study of 356 Canadian atrial arrhythmia patients seen in emergency settings.
One way to deal with potentially inappropriate emergency department use is to have concerned patients with atrial fibrillation (AF) record their heart rhythm data with a handheld device or watch, transfer the records to their smartphones, and transmit the information to a remote physician for interpretation and advice, Benedict M. Glover, MD, said at the annual International AF Symposium.
Dr. Glover and his associates are in the process of developing a prototype system of this design to address the need they identified in a recent registry of 356 patients with a primary diagnosis of AF who sought care in the emergency department (ED) of any of seven participating Canadian medical centers, including five academic centers and two community hospitals. The survey results showed that 71% of the patients were symptomatic and 29% were asymptomatic then they first presented to an emergency department.
Case reviews of the 356 patients showed that 152 (43%) came to the EDs for what were classified as inappropriate reasons. The most common cause by far of an inappropriate emergency presentation was prior medical advice the patient had received, cited in 62% of the inappropriate cases, compared with 9% of the appropriate cases, said Dr. Glover, an electrophysiologist at Sunnybrook Health Sciences Centre in Toronto.
The inappropriate ED use by AF patients could be addressed in at least two ways, he said. One solution might be to give patients an alternative destination, so that instead of going to an emergency department they could go to an outpatient AF clinic. A second solution is to give patients a way to have their heart rhythm assessed remotely at the time of their concern. Dr. Glover said that his center had the staff capacity to deal with the potential influx of rhythm data from a pilot-sized program of remote heart-rhythm monitoring, but he conceded that scaling up to deal with the data that could come from the entire panel of AF patients managed by Sunnybrook physicians would be a huge challenge.
“The issue is what do we do with the data after we get it,” Dr. Glover said. “It’s a lot of information.”
Dr. Glover had no disclosures.
BOSTON – Patients with atrial fibrillation who present to emergency departments, despite being asymptomatic, often go based on of their understanding of advice they had previously received from their physicians, according to results from a prospective study of 356 Canadian atrial arrhythmia patients seen in emergency settings.
One way to deal with potentially inappropriate emergency department use is to have concerned patients with atrial fibrillation (AF) record their heart rhythm data with a handheld device or watch, transfer the records to their smartphones, and transmit the information to a remote physician for interpretation and advice, Benedict M. Glover, MD, said at the annual International AF Symposium.
Dr. Glover and his associates are in the process of developing a prototype system of this design to address the need they identified in a recent registry of 356 patients with a primary diagnosis of AF who sought care in the emergency department (ED) of any of seven participating Canadian medical centers, including five academic centers and two community hospitals. The survey results showed that 71% of the patients were symptomatic and 29% were asymptomatic then they first presented to an emergency department.
Case reviews of the 356 patients showed that 152 (43%) came to the EDs for what were classified as inappropriate reasons. The most common cause by far of an inappropriate emergency presentation was prior medical advice the patient had received, cited in 62% of the inappropriate cases, compared with 9% of the appropriate cases, said Dr. Glover, an electrophysiologist at Sunnybrook Health Sciences Centre in Toronto.
The inappropriate ED use by AF patients could be addressed in at least two ways, he said. One solution might be to give patients an alternative destination, so that instead of going to an emergency department they could go to an outpatient AF clinic. A second solution is to give patients a way to have their heart rhythm assessed remotely at the time of their concern. Dr. Glover said that his center had the staff capacity to deal with the potential influx of rhythm data from a pilot-sized program of remote heart-rhythm monitoring, but he conceded that scaling up to deal with the data that could come from the entire panel of AF patients managed by Sunnybrook physicians would be a huge challenge.
“The issue is what do we do with the data after we get it,” Dr. Glover said. “It’s a lot of information.”
Dr. Glover had no disclosures.
BOSTON – Patients with atrial fibrillation who present to emergency departments, despite being asymptomatic, often go based on of their understanding of advice they had previously received from their physicians, according to results from a prospective study of 356 Canadian atrial arrhythmia patients seen in emergency settings.
One way to deal with potentially inappropriate emergency department use is to have concerned patients with atrial fibrillation (AF) record their heart rhythm data with a handheld device or watch, transfer the records to their smartphones, and transmit the information to a remote physician for interpretation and advice, Benedict M. Glover, MD, said at the annual International AF Symposium.
Dr. Glover and his associates are in the process of developing a prototype system of this design to address the need they identified in a recent registry of 356 patients with a primary diagnosis of AF who sought care in the emergency department (ED) of any of seven participating Canadian medical centers, including five academic centers and two community hospitals. The survey results showed that 71% of the patients were symptomatic and 29% were asymptomatic then they first presented to an emergency department.
Case reviews of the 356 patients showed that 152 (43%) came to the EDs for what were classified as inappropriate reasons. The most common cause by far of an inappropriate emergency presentation was prior medical advice the patient had received, cited in 62% of the inappropriate cases, compared with 9% of the appropriate cases, said Dr. Glover, an electrophysiologist at Sunnybrook Health Sciences Centre in Toronto.
The inappropriate ED use by AF patients could be addressed in at least two ways, he said. One solution might be to give patients an alternative destination, so that instead of going to an emergency department they could go to an outpatient AF clinic. A second solution is to give patients a way to have their heart rhythm assessed remotely at the time of their concern. Dr. Glover said that his center had the staff capacity to deal with the potential influx of rhythm data from a pilot-sized program of remote heart-rhythm monitoring, but he conceded that scaling up to deal with the data that could come from the entire panel of AF patients managed by Sunnybrook physicians would be a huge challenge.
“The issue is what do we do with the data after we get it,” Dr. Glover said. “It’s a lot of information.”
Dr. Glover had no disclosures.
REPORTING FROM THE AF SYMPOSIUM 2019
Key clinical point:
Major finding: Among 152 AF patients who made an inappropriate ED visit, 62% cited their prior medical advice.
Study details: Prospective study of 356 AF patients who sought ED care at any of seven Canadian hospitals.
Disclosures: Dr. Glover had no disclosures.
Atrial mapping device drives more thorough AF ablations
BOSTON – An atrial mapping catheter that combines ultrasound anatomic mapping with nontouch, high-resolution, charge-density mapping resulted in a high, 73% freedom from recurrent atrial fibrillation rate 12 months after ablation procedures guided by this catheter in a single-arm, multicenter study with 121 patients with persistent atrial fibrillation followed for 1 year.
The AcQMap device tested in the study “allows you to quickly remap” the left atrium after an initial pulmonary vein isolation or after other types of ablations to find remaining areas of abnormal electrical activity on the atrial walls and then “go after those,” Atul Verma, MD, said at the annual International AF Symposium.
An analysis he reported showed that the single patient variable that linked with the highest rate of 1-year freedom from recurrent atrial fibrillation (AF) was having at least three atrial targets ablated in addition to pulmonary vein isolation. Patients who received this number of added ablations were more than nine times more likely to be free from AF after 12 months, compared with patients who received fewer additional ablations, said Dr. Verma, a cardiac electrophysiologist at Southlake Regional Health Centre in Newmarket, Ont.
The AcQMap catheter “identifies more places to ablate.” What makes it unique among currently available mapping devices is its high resolution, its use of charge-density mapping rather than voltage-based mapping, and its speed, Dr. Verma said in an interview.
The AcQMap device has Food and Drug Administration marketing approval for mapping and so is available for routine U.S. use. However, Dr. Verma cautioned that the increased freedom from persistent AF after using the catheter during ablation that he reported should be confirmed by a randomized trial. Another electrophysiologist who performs ablations but was not involved with the study, Vivek Reddy, MD, agreed with this caveat.
“Nonrandomized trials of ablation in patients with persistent AF are at best hypothesis generating. We’ve learned that the hard way; we have been burned too many times. To assess mapping of AF activity you need a randomized, controlled trial,” said Dr. Reddy, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.
The UNCOVER-AF (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) study ran at 13 centers in Canada and Europe and enrolled 129 patients who had persistent AF for an average of almost 2 years, of whom 127 actually underwent an ablation procedure and 121 were followed for 12 months post ablation. Operators were free to use the AcQMap device to map the left atrium as many times as they thought necessary, generally once at the start of the procedure, a second time after they completed pulmonary vein isolation, and then a variable number of subsequent times. On average they performed about four mappings in each patient. At entry, patients had received an average of one antiarrhythmic drug. After their ablation treatment, about 10% of patients received an antiarrhythmic drug.
The investigators found no major adverse events linked to use of the mapping device. Three patients had major adverse events related to the overall ablation procedure: Two developed cardiac tamponade, and one had a stroke. No patients had an esophageal fistula or symptomatic pulmonary vein stenosis.
After the single ablation procedure and at 12-month follow-up, the prevalence of freedom from recurrent AF was 73%, and freedom from any atrial arrhythmia was 69%. As a historical comparison, Dr. Verma cited the 12-month outcome following pulmonary vein isolation and other ablative measures in the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) trial, which reported a 59% freedom from AF rate and a 49% freedom from any atrial arrhythmia rate with or without antiarrhythmic drug treatment after pulmonary vein isolation (N Engl J Med. 2015 May 7;372[19]:1812-22).
Multivariate analysis of the new data showed that, in addition to ablation of three or more targets, two other variables also linked significantly with long-term freedom from AF: Ablation of at least two types of electrical abnormalities in the left atrial wall, which boosted the 12-month AF-free rate by 2.8 fold, and being in sinus rhythm at the start of the ablation procedure, which linked with a 5-fold higher rate of long-term freedom from AF.
Dr. Verma also reported the AF burden measured after ablation in 96 patients who each underwent an average of 85 hours of postablation heart rhythm monitoring. Ninety percent of these patients showed no AF episodes of more than 30 seconds throughout the duration of their monitoring.
UNCOVER-AF was funded by Acutus, the company that markets the AcQMap catheter. Dr. Verma has been an advisor to or speaker on behalf of Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic, and St. Jude (Abbott), and he has received research funding from Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic. He had no personal disclosures relative to Acutus. Dr. Reddy has been a consultant to, received research funding from, and has an equity stake in Acutus, and has similar relationships with more than three dozen other companies.
BOSTON – An atrial mapping catheter that combines ultrasound anatomic mapping with nontouch, high-resolution, charge-density mapping resulted in a high, 73% freedom from recurrent atrial fibrillation rate 12 months after ablation procedures guided by this catheter in a single-arm, multicenter study with 121 patients with persistent atrial fibrillation followed for 1 year.
The AcQMap device tested in the study “allows you to quickly remap” the left atrium after an initial pulmonary vein isolation or after other types of ablations to find remaining areas of abnormal electrical activity on the atrial walls and then “go after those,” Atul Verma, MD, said at the annual International AF Symposium.
An analysis he reported showed that the single patient variable that linked with the highest rate of 1-year freedom from recurrent atrial fibrillation (AF) was having at least three atrial targets ablated in addition to pulmonary vein isolation. Patients who received this number of added ablations were more than nine times more likely to be free from AF after 12 months, compared with patients who received fewer additional ablations, said Dr. Verma, a cardiac electrophysiologist at Southlake Regional Health Centre in Newmarket, Ont.
The AcQMap catheter “identifies more places to ablate.” What makes it unique among currently available mapping devices is its high resolution, its use of charge-density mapping rather than voltage-based mapping, and its speed, Dr. Verma said in an interview.
The AcQMap device has Food and Drug Administration marketing approval for mapping and so is available for routine U.S. use. However, Dr. Verma cautioned that the increased freedom from persistent AF after using the catheter during ablation that he reported should be confirmed by a randomized trial. Another electrophysiologist who performs ablations but was not involved with the study, Vivek Reddy, MD, agreed with this caveat.
“Nonrandomized trials of ablation in patients with persistent AF are at best hypothesis generating. We’ve learned that the hard way; we have been burned too many times. To assess mapping of AF activity you need a randomized, controlled trial,” said Dr. Reddy, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.
The UNCOVER-AF (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) study ran at 13 centers in Canada and Europe and enrolled 129 patients who had persistent AF for an average of almost 2 years, of whom 127 actually underwent an ablation procedure and 121 were followed for 12 months post ablation. Operators were free to use the AcQMap device to map the left atrium as many times as they thought necessary, generally once at the start of the procedure, a second time after they completed pulmonary vein isolation, and then a variable number of subsequent times. On average they performed about four mappings in each patient. At entry, patients had received an average of one antiarrhythmic drug. After their ablation treatment, about 10% of patients received an antiarrhythmic drug.
The investigators found no major adverse events linked to use of the mapping device. Three patients had major adverse events related to the overall ablation procedure: Two developed cardiac tamponade, and one had a stroke. No patients had an esophageal fistula or symptomatic pulmonary vein stenosis.
After the single ablation procedure and at 12-month follow-up, the prevalence of freedom from recurrent AF was 73%, and freedom from any atrial arrhythmia was 69%. As a historical comparison, Dr. Verma cited the 12-month outcome following pulmonary vein isolation and other ablative measures in the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) trial, which reported a 59% freedom from AF rate and a 49% freedom from any atrial arrhythmia rate with or without antiarrhythmic drug treatment after pulmonary vein isolation (N Engl J Med. 2015 May 7;372[19]:1812-22).
Multivariate analysis of the new data showed that, in addition to ablation of three or more targets, two other variables also linked significantly with long-term freedom from AF: Ablation of at least two types of electrical abnormalities in the left atrial wall, which boosted the 12-month AF-free rate by 2.8 fold, and being in sinus rhythm at the start of the ablation procedure, which linked with a 5-fold higher rate of long-term freedom from AF.
Dr. Verma also reported the AF burden measured after ablation in 96 patients who each underwent an average of 85 hours of postablation heart rhythm monitoring. Ninety percent of these patients showed no AF episodes of more than 30 seconds throughout the duration of their monitoring.
UNCOVER-AF was funded by Acutus, the company that markets the AcQMap catheter. Dr. Verma has been an advisor to or speaker on behalf of Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic, and St. Jude (Abbott), and he has received research funding from Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic. He had no personal disclosures relative to Acutus. Dr. Reddy has been a consultant to, received research funding from, and has an equity stake in Acutus, and has similar relationships with more than three dozen other companies.
BOSTON – An atrial mapping catheter that combines ultrasound anatomic mapping with nontouch, high-resolution, charge-density mapping resulted in a high, 73% freedom from recurrent atrial fibrillation rate 12 months after ablation procedures guided by this catheter in a single-arm, multicenter study with 121 patients with persistent atrial fibrillation followed for 1 year.
The AcQMap device tested in the study “allows you to quickly remap” the left atrium after an initial pulmonary vein isolation or after other types of ablations to find remaining areas of abnormal electrical activity on the atrial walls and then “go after those,” Atul Verma, MD, said at the annual International AF Symposium.
An analysis he reported showed that the single patient variable that linked with the highest rate of 1-year freedom from recurrent atrial fibrillation (AF) was having at least three atrial targets ablated in addition to pulmonary vein isolation. Patients who received this number of added ablations were more than nine times more likely to be free from AF after 12 months, compared with patients who received fewer additional ablations, said Dr. Verma, a cardiac electrophysiologist at Southlake Regional Health Centre in Newmarket, Ont.
The AcQMap catheter “identifies more places to ablate.” What makes it unique among currently available mapping devices is its high resolution, its use of charge-density mapping rather than voltage-based mapping, and its speed, Dr. Verma said in an interview.
The AcQMap device has Food and Drug Administration marketing approval for mapping and so is available for routine U.S. use. However, Dr. Verma cautioned that the increased freedom from persistent AF after using the catheter during ablation that he reported should be confirmed by a randomized trial. Another electrophysiologist who performs ablations but was not involved with the study, Vivek Reddy, MD, agreed with this caveat.
“Nonrandomized trials of ablation in patients with persistent AF are at best hypothesis generating. We’ve learned that the hard way; we have been burned too many times. To assess mapping of AF activity you need a randomized, controlled trial,” said Dr. Reddy, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.
The UNCOVER-AF (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) study ran at 13 centers in Canada and Europe and enrolled 129 patients who had persistent AF for an average of almost 2 years, of whom 127 actually underwent an ablation procedure and 121 were followed for 12 months post ablation. Operators were free to use the AcQMap device to map the left atrium as many times as they thought necessary, generally once at the start of the procedure, a second time after they completed pulmonary vein isolation, and then a variable number of subsequent times. On average they performed about four mappings in each patient. At entry, patients had received an average of one antiarrhythmic drug. After their ablation treatment, about 10% of patients received an antiarrhythmic drug.
The investigators found no major adverse events linked to use of the mapping device. Three patients had major adverse events related to the overall ablation procedure: Two developed cardiac tamponade, and one had a stroke. No patients had an esophageal fistula or symptomatic pulmonary vein stenosis.
After the single ablation procedure and at 12-month follow-up, the prevalence of freedom from recurrent AF was 73%, and freedom from any atrial arrhythmia was 69%. As a historical comparison, Dr. Verma cited the 12-month outcome following pulmonary vein isolation and other ablative measures in the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) trial, which reported a 59% freedom from AF rate and a 49% freedom from any atrial arrhythmia rate with or without antiarrhythmic drug treatment after pulmonary vein isolation (N Engl J Med. 2015 May 7;372[19]:1812-22).
Multivariate analysis of the new data showed that, in addition to ablation of three or more targets, two other variables also linked significantly with long-term freedom from AF: Ablation of at least two types of electrical abnormalities in the left atrial wall, which boosted the 12-month AF-free rate by 2.8 fold, and being in sinus rhythm at the start of the ablation procedure, which linked with a 5-fold higher rate of long-term freedom from AF.
Dr. Verma also reported the AF burden measured after ablation in 96 patients who each underwent an average of 85 hours of postablation heart rhythm monitoring. Ninety percent of these patients showed no AF episodes of more than 30 seconds throughout the duration of their monitoring.
UNCOVER-AF was funded by Acutus, the company that markets the AcQMap catheter. Dr. Verma has been an advisor to or speaker on behalf of Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic, and St. Jude (Abbott), and he has received research funding from Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic. He had no personal disclosures relative to Acutus. Dr. Reddy has been a consultant to, received research funding from, and has an equity stake in Acutus, and has similar relationships with more than three dozen other companies.
REPORTING FROM THE AF SYMPOSIUM 2019
Key clinical point: The 1-year success of AF ablation surpassed historical controls when operators used a new mapping catheter.
Major finding: Freedom from atrial fibrillation after 1 year was 73% when operators used the AcQMap catheter during ablation procedures.
Study details: UNCOVER-AF, a single-arm, multicenter study with 121 patients with persistent atrial fibrillation ablated and followed for 12 months.
Disclosures: UNCOVER-AF was funded by Acutus, the company that markets the AcQMap catheter. Dr. Verma has been an advisor to or speaker on behalf of Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic, and St. Jude (Abbott), and he has received research funding from Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic. He had no personal disclosures relative to Acutus. Dr. Reddy has been a consultant to, received research funding from, and has an equity stake in Acutus, and has similar relationships with more than three dozen other companies.
LAA closure safely treated AF patients with prior ICH
BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.
“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.
Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.
Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.
The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.
Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.
During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.
At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.
A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).
BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.
“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.
Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.
Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.
The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.
Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.
During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.
At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.
A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).
BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.
“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.
Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.
Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.
The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.
Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.
During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.
At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.
A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).
REPORTING FROM THE AF SYMPOSIUM 2019
Key clinical point: Tailoring the anticlotting regimen atrial fibrillation (AF) patients received after left atrial appendage (LAA) closure led to good outcomes despite prior intracranial hemorrhages.
Major finding: The 6-month rate of death, stroke, or major bleed was about 5% in AF patients who underwent LAA closure after intracranial hemorrhage.
Study details: Retrospective review of 158 atrial fibrillation patients who underwent LAA closure at any of three U.S. centers.
Disclosures: The study received no commercial funding. Dr. Mansour has been a consultant to Abbott, Biosense Webster, Boston Scientific, and Medtronic; he has received research funding from Abbott, Biosense Webster, Boehringer Ingelheim, Boston Scientific, and Pfizer; and he has an equity interest in EPD Solutions and NewPace.
CABANA: Ablation surpassed drugs for raising AF quality of life
BOSTON – Ablation of atrial fibrillation led to significantly better quality of life improvements, compared with antiarrhythmic drug therapy, in a prespecified, secondary analysis of data from the CABANA multicenter, randomized trial with 2,204 patients.
The improvements in quality of life measures in atrial fibrillation (AF) patients following ablation were “clinically meaningful” relative to drug therapy and were sustained for 5 years of follow-up, said Douglas L. Packer, MD, at the annual International AF Symposium.
The apparent incremental benefit in quality of life after ablation, compared with patients treated with drug therapy, added to the benefits previously reported from CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) using ablation that included a highly significant reduction in recurrent AF and a significant reduction in the combined endpoint of mortality or cardiovascular hospitalization. However, the trial’s results were neutral for the study’s prespecified primary endpoint, a combination of the rate of total mortality, disabling stroke, serious bleeding, or cardiac arrest in an intention-to-treat analysis, a result first reported by Dr. Packer at the annual scientific sessions of the Heart Rhythm Society in May 2018.
When Dr. Packer spoke at the AF Symposium in late January 2019, the CABANA results had still not been published. He said that he expected an article with the main findings to appear online sometime in February 2019.
The quality of life analysis, focused on two measures, the Mayo AF-Specific Symptoms Inventory (MAFSI) (Circulation. 2008 Oct 28;118[suppl 18]:S589) and the Atrial Fibrillation Affect on Quality of Life (AFEQT) (Circ Arrhythm Electrophysiol. 2011 Feb;4[1]:15-25). The patients enrolled in the two treatment arms of CABANA had essentially identical baseline MAFSI frequency scores, but starting 3 months after entry patients randomized to the ablation arm had an average, statistically significant 1.6-point improvement in their adjusted MAFSI frequency score, compared with patients in the drug-therapy arm; this reduction persisted at about the same statistically significant level through 5 years, said Dr. Packer, an electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of CABANA. Patients who remained in follow-up throughout the study’s entire 60 months underwent a total of seven MAFSI assessments after their initial treatment; the average, adjusted difference in MAFSI frequency scores throughout CABANA was a statistically significant 1.4 points lower among ablated patients, compared with those randomized to drug therapy, said Dr. Packer, who presented data first reported by the CABANA researchers in 2018.
The pattern of change in the AFEQT scores was very similar. The average, adjusted AFEQT summary scores were virtually identical at baseline for the two treatment arms, but at 3 months after the study began patients in the ablation arm had an average, adjusted, statistically significant 3-point improvement in their AFEQT summary scores, compared with drug-treated patients; this incremental increase in AFEQT scores remained consistent and statistically significant through 5 years of follow-up. Throughout the study, the average, adjusted, incremental improvement in AFEQT after ablation was a statistically significant 3.4 points, said Dr. Packer.
But these quality of life measures in patients who received unblinded assignment to an ablation procedure or drug treatment in CABANA are likely unreliable, commented Peter R. Kowey, MD, an electrophysiologist at the Lankenau Heart Institute in Wynnewood, Penn., and professor of medicine at Jefferson Medical College, Philadelphia.
“Assessing quality of life in an unblinded trial seems to me to be pretty shallow,” said Dr. Kowey, a member of the CABANA steering committee and a participant in a panel at the Symposium that discussed the results. Patients who have just gone through a 6-hour procedure will often say they now feel a whole lot better, he suggested. “They’re concerned what will get done to them if they don’t say they feel better.” The same confounding also applies to other “soft” secondary endpoints used in CABANA, such as hospitalization rates.
The reliability of these more subjective outcome measures is reduced in an unblinded trial, Dr. Kowey maintained. The CABANA results “don’t change the fundamental principal of using hard endpoints,” such as those that made up the primary endpoint of the study, he said in an interview. “We put secondary endpoints into the study because they are legitimate things to look at, but they have questionable reliability,” as measures of ablation’s efficacy.
Dr. Kowey also cautioned against focusing on the per-protocol and treatment-received analyses of the CABANA results, prespecified analyses that Dr. Packer highlighted because of the high number of crossovers in the trial: 9% of patients assigned to ablation never received it and 28% of patients assigned to drug therapy actually received ablation.
The CABANA steering committee anticipated a high crossover rate, but still set the intention-to-treat analysis as primary because “per protocol introduces many biases and can’t be relied on for a study of this magnitude,” Dr. Kowey said. He also cited the statistical pitfalls of looking at multiple secondary endpoints in the CABANA results and the danger of reading too much into subgroup analyses, all from a trial with a neutral primary endpoint.
Another concern he raised centered on the generalizability of CABANA’s safety findings, which showed roughly similar adverse event rates between the two treatment arms – about 9% with ablation, 4% with drugs – although the distribution of complications types differed between the two arms. The “ ‘remarkably safe’ performance of ablation in CABANA can be attributed to ‘cherry-picked’ investigators” who performed the ablation procedures at high-volume centers, said Dr. Kowey. “The safety of ablation was predictable” in CABANA because of the selection of participating centers. “Seventy percent of U.S. ablations are being done at centers that do fewer than 25 ablations annually,” Dr. Kowey said. “We don’t know what goes on” at lower-volume centers; “ablation can’t be considered as safe as we presume” when done at centers outside the 118 sites that participated in CABANA, he maintained.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to these four companies as well as to CyberHeart, nContact, Sanofi-Aventis, and Toray. He has received research funding from AG, Biosense Webster, Boston Scientific, CryoCath, EP Limited, and Medtronic, and has a financial interest in AF mapping technology. Dr. Kowey has been a consultant to several companies that market antiarrhythmic drugs or market arrhythmia devices and has an equity interest in BioTelemetry.
BOSTON – Ablation of atrial fibrillation led to significantly better quality of life improvements, compared with antiarrhythmic drug therapy, in a prespecified, secondary analysis of data from the CABANA multicenter, randomized trial with 2,204 patients.
The improvements in quality of life measures in atrial fibrillation (AF) patients following ablation were “clinically meaningful” relative to drug therapy and were sustained for 5 years of follow-up, said Douglas L. Packer, MD, at the annual International AF Symposium.
The apparent incremental benefit in quality of life after ablation, compared with patients treated with drug therapy, added to the benefits previously reported from CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) using ablation that included a highly significant reduction in recurrent AF and a significant reduction in the combined endpoint of mortality or cardiovascular hospitalization. However, the trial’s results were neutral for the study’s prespecified primary endpoint, a combination of the rate of total mortality, disabling stroke, serious bleeding, or cardiac arrest in an intention-to-treat analysis, a result first reported by Dr. Packer at the annual scientific sessions of the Heart Rhythm Society in May 2018.
When Dr. Packer spoke at the AF Symposium in late January 2019, the CABANA results had still not been published. He said that he expected an article with the main findings to appear online sometime in February 2019.
The quality of life analysis, focused on two measures, the Mayo AF-Specific Symptoms Inventory (MAFSI) (Circulation. 2008 Oct 28;118[suppl 18]:S589) and the Atrial Fibrillation Affect on Quality of Life (AFEQT) (Circ Arrhythm Electrophysiol. 2011 Feb;4[1]:15-25). The patients enrolled in the two treatment arms of CABANA had essentially identical baseline MAFSI frequency scores, but starting 3 months after entry patients randomized to the ablation arm had an average, statistically significant 1.6-point improvement in their adjusted MAFSI frequency score, compared with patients in the drug-therapy arm; this reduction persisted at about the same statistically significant level through 5 years, said Dr. Packer, an electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of CABANA. Patients who remained in follow-up throughout the study’s entire 60 months underwent a total of seven MAFSI assessments after their initial treatment; the average, adjusted difference in MAFSI frequency scores throughout CABANA was a statistically significant 1.4 points lower among ablated patients, compared with those randomized to drug therapy, said Dr. Packer, who presented data first reported by the CABANA researchers in 2018.
The pattern of change in the AFEQT scores was very similar. The average, adjusted AFEQT summary scores were virtually identical at baseline for the two treatment arms, but at 3 months after the study began patients in the ablation arm had an average, adjusted, statistically significant 3-point improvement in their AFEQT summary scores, compared with drug-treated patients; this incremental increase in AFEQT scores remained consistent and statistically significant through 5 years of follow-up. Throughout the study, the average, adjusted, incremental improvement in AFEQT after ablation was a statistically significant 3.4 points, said Dr. Packer.
But these quality of life measures in patients who received unblinded assignment to an ablation procedure or drug treatment in CABANA are likely unreliable, commented Peter R. Kowey, MD, an electrophysiologist at the Lankenau Heart Institute in Wynnewood, Penn., and professor of medicine at Jefferson Medical College, Philadelphia.
“Assessing quality of life in an unblinded trial seems to me to be pretty shallow,” said Dr. Kowey, a member of the CABANA steering committee and a participant in a panel at the Symposium that discussed the results. Patients who have just gone through a 6-hour procedure will often say they now feel a whole lot better, he suggested. “They’re concerned what will get done to them if they don’t say they feel better.” The same confounding also applies to other “soft” secondary endpoints used in CABANA, such as hospitalization rates.
The reliability of these more subjective outcome measures is reduced in an unblinded trial, Dr. Kowey maintained. The CABANA results “don’t change the fundamental principal of using hard endpoints,” such as those that made up the primary endpoint of the study, he said in an interview. “We put secondary endpoints into the study because they are legitimate things to look at, but they have questionable reliability,” as measures of ablation’s efficacy.
Dr. Kowey also cautioned against focusing on the per-protocol and treatment-received analyses of the CABANA results, prespecified analyses that Dr. Packer highlighted because of the high number of crossovers in the trial: 9% of patients assigned to ablation never received it and 28% of patients assigned to drug therapy actually received ablation.
The CABANA steering committee anticipated a high crossover rate, but still set the intention-to-treat analysis as primary because “per protocol introduces many biases and can’t be relied on for a study of this magnitude,” Dr. Kowey said. He also cited the statistical pitfalls of looking at multiple secondary endpoints in the CABANA results and the danger of reading too much into subgroup analyses, all from a trial with a neutral primary endpoint.
Another concern he raised centered on the generalizability of CABANA’s safety findings, which showed roughly similar adverse event rates between the two treatment arms – about 9% with ablation, 4% with drugs – although the distribution of complications types differed between the two arms. The “ ‘remarkably safe’ performance of ablation in CABANA can be attributed to ‘cherry-picked’ investigators” who performed the ablation procedures at high-volume centers, said Dr. Kowey. “The safety of ablation was predictable” in CABANA because of the selection of participating centers. “Seventy percent of U.S. ablations are being done at centers that do fewer than 25 ablations annually,” Dr. Kowey said. “We don’t know what goes on” at lower-volume centers; “ablation can’t be considered as safe as we presume” when done at centers outside the 118 sites that participated in CABANA, he maintained.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to these four companies as well as to CyberHeart, nContact, Sanofi-Aventis, and Toray. He has received research funding from AG, Biosense Webster, Boston Scientific, CryoCath, EP Limited, and Medtronic, and has a financial interest in AF mapping technology. Dr. Kowey has been a consultant to several companies that market antiarrhythmic drugs or market arrhythmia devices and has an equity interest in BioTelemetry.
BOSTON – Ablation of atrial fibrillation led to significantly better quality of life improvements, compared with antiarrhythmic drug therapy, in a prespecified, secondary analysis of data from the CABANA multicenter, randomized trial with 2,204 patients.
The improvements in quality of life measures in atrial fibrillation (AF) patients following ablation were “clinically meaningful” relative to drug therapy and were sustained for 5 years of follow-up, said Douglas L. Packer, MD, at the annual International AF Symposium.
The apparent incremental benefit in quality of life after ablation, compared with patients treated with drug therapy, added to the benefits previously reported from CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) using ablation that included a highly significant reduction in recurrent AF and a significant reduction in the combined endpoint of mortality or cardiovascular hospitalization. However, the trial’s results were neutral for the study’s prespecified primary endpoint, a combination of the rate of total mortality, disabling stroke, serious bleeding, or cardiac arrest in an intention-to-treat analysis, a result first reported by Dr. Packer at the annual scientific sessions of the Heart Rhythm Society in May 2018.
When Dr. Packer spoke at the AF Symposium in late January 2019, the CABANA results had still not been published. He said that he expected an article with the main findings to appear online sometime in February 2019.
The quality of life analysis, focused on two measures, the Mayo AF-Specific Symptoms Inventory (MAFSI) (Circulation. 2008 Oct 28;118[suppl 18]:S589) and the Atrial Fibrillation Affect on Quality of Life (AFEQT) (Circ Arrhythm Electrophysiol. 2011 Feb;4[1]:15-25). The patients enrolled in the two treatment arms of CABANA had essentially identical baseline MAFSI frequency scores, but starting 3 months after entry patients randomized to the ablation arm had an average, statistically significant 1.6-point improvement in their adjusted MAFSI frequency score, compared with patients in the drug-therapy arm; this reduction persisted at about the same statistically significant level through 5 years, said Dr. Packer, an electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of CABANA. Patients who remained in follow-up throughout the study’s entire 60 months underwent a total of seven MAFSI assessments after their initial treatment; the average, adjusted difference in MAFSI frequency scores throughout CABANA was a statistically significant 1.4 points lower among ablated patients, compared with those randomized to drug therapy, said Dr. Packer, who presented data first reported by the CABANA researchers in 2018.
The pattern of change in the AFEQT scores was very similar. The average, adjusted AFEQT summary scores were virtually identical at baseline for the two treatment arms, but at 3 months after the study began patients in the ablation arm had an average, adjusted, statistically significant 3-point improvement in their AFEQT summary scores, compared with drug-treated patients; this incremental increase in AFEQT scores remained consistent and statistically significant through 5 years of follow-up. Throughout the study, the average, adjusted, incremental improvement in AFEQT after ablation was a statistically significant 3.4 points, said Dr. Packer.
But these quality of life measures in patients who received unblinded assignment to an ablation procedure or drug treatment in CABANA are likely unreliable, commented Peter R. Kowey, MD, an electrophysiologist at the Lankenau Heart Institute in Wynnewood, Penn., and professor of medicine at Jefferson Medical College, Philadelphia.
“Assessing quality of life in an unblinded trial seems to me to be pretty shallow,” said Dr. Kowey, a member of the CABANA steering committee and a participant in a panel at the Symposium that discussed the results. Patients who have just gone through a 6-hour procedure will often say they now feel a whole lot better, he suggested. “They’re concerned what will get done to them if they don’t say they feel better.” The same confounding also applies to other “soft” secondary endpoints used in CABANA, such as hospitalization rates.
The reliability of these more subjective outcome measures is reduced in an unblinded trial, Dr. Kowey maintained. The CABANA results “don’t change the fundamental principal of using hard endpoints,” such as those that made up the primary endpoint of the study, he said in an interview. “We put secondary endpoints into the study because they are legitimate things to look at, but they have questionable reliability,” as measures of ablation’s efficacy.
Dr. Kowey also cautioned against focusing on the per-protocol and treatment-received analyses of the CABANA results, prespecified analyses that Dr. Packer highlighted because of the high number of crossovers in the trial: 9% of patients assigned to ablation never received it and 28% of patients assigned to drug therapy actually received ablation.
The CABANA steering committee anticipated a high crossover rate, but still set the intention-to-treat analysis as primary because “per protocol introduces many biases and can’t be relied on for a study of this magnitude,” Dr. Kowey said. He also cited the statistical pitfalls of looking at multiple secondary endpoints in the CABANA results and the danger of reading too much into subgroup analyses, all from a trial with a neutral primary endpoint.
Another concern he raised centered on the generalizability of CABANA’s safety findings, which showed roughly similar adverse event rates between the two treatment arms – about 9% with ablation, 4% with drugs – although the distribution of complications types differed between the two arms. The “ ‘remarkably safe’ performance of ablation in CABANA can be attributed to ‘cherry-picked’ investigators” who performed the ablation procedures at high-volume centers, said Dr. Kowey. “The safety of ablation was predictable” in CABANA because of the selection of participating centers. “Seventy percent of U.S. ablations are being done at centers that do fewer than 25 ablations annually,” Dr. Kowey said. “We don’t know what goes on” at lower-volume centers; “ablation can’t be considered as safe as we presume” when done at centers outside the 118 sites that participated in CABANA, he maintained.
CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to these four companies as well as to CyberHeart, nContact, Sanofi-Aventis, and Toray. He has received research funding from AG, Biosense Webster, Boston Scientific, CryoCath, EP Limited, and Medtronic, and has a financial interest in AF mapping technology. Dr. Kowey has been a consultant to several companies that market antiarrhythmic drugs or market arrhythmia devices and has an equity interest in BioTelemetry.
REPORTING FROM THE AF SYMPOSIUM 2019
Key clinical point: In CABANA, atrial fibrillation ablation led to a clinically meaningful improvement of quality of life measures, compared with drug therapy.
Major finding: After ablation, the MAFSI score averaged a 1.4-point improvement; the AFEQT score averaged a 3.4-point improvement over drug therapy.
Study details: CABANA, a multicenter, randomized trial with 2,204 atrial fibrillation patients.
Disclosures: CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to these four companies as well as to CyberHeart, nContact, Sanofi-Aventis, and Toray. He has received research funding from AG, Biosense Webster, Boston Scientific, CryoCath, EP Limited, and Medtronic, and has a financial interest in atrial fibrillation mapping technology. Dr. Kowey has been a consultant to several companies that market antiarrhythmic drugs or market arrhythmia devices and has an equity interest in BioTelemetry.