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AFib patients do best on a DOAC started 7-10 days post stroke
LOS ANGELES – When a patient with atrial fibrillation (AFib) has a cardioembolic stroke, the best blood thinner to start may be a direct-acting oral anticoagulant (DOAC), possibly beginning 7-10 days after the index stroke, according to an analysis of 90-day, observational outcomes data from nearly 1,300 patients.
The analysis also suggested that the use of “bridging” anticoagulant treatment by injection before a patient with atrial fibrillation (AFib) starts a daily oral anticoagulant regimen following a cardioembolic stroke is not a good idea. Patients who received bridging anticoagulation had a nearly threefold higher rate of symptomatic intracranial hemorrhage than did patients who did not, and their bridging treatment failed to protect them from recurrent ischemic events, Shadi Yaghi, MD, said at the International Stroke Conference, sponsored by the American Heart Association. The bridging regimens delivered either heparin or low-molecular-weight heparin.
Based on the findings, “it seems reasonable to avoid bridging unless absolutely necessary, to initiate a DOAC unless it’s contraindicated, and to start the DOAC on day 7-10 following the stroke in most patients,” said Dr. Yaghi, a vascular neurologist and director of stroke research at NYU Langone Health in New York.
“It’s been hard to develop a broad guideline on when to start oral anticoagulation” after a cardioembolic stroke in AFib patients. The best time “depends on a lot of variables and how the patient responded to acute treatment,” commented Alexis Simpkins, MD, a vascular and stroke neurologist at the University of Florida in Gainesville. “You want to start treatment before the patient has another stroke, but not so soon that the treatment causes symptomatic hemorrhagic transformation.”
Dr. Yaghi’s suggestion, based on his findings, to start treatment for most patients with a DOAC 7-10 days after their index stroke “shows consistency” with the prevailing guideline recommendation from the AHA/American Stroke Association to start oral anticoagulation in this patient population 4-14 days after the index stroke (Stroke. 2018 March;49[3]:e46-e99), she noted.
A recent article reviewed the uncertainty about the best time to start oral anticoagulation in AFib patients after a cardioembolic stroke and the subtle differences that distinguish various international medical groups that, like the ASA, have made recommendations (Lancet Neurol. 2019 Jan 1;18[1]:117-26). According to this review, a major limitation of these various recommendations has been the lack of actual evidence collected from AFib patients who began receiving a DOAC shortly after a cardioembolic stroke, although the article added that several studies in progress are collecting these data.
The study reported by Dr. Yaghi pooled data collected from 2,084 recent AFib patients with a cardioembolic stroke treated at any of eight comprehensive U.S. stroke centers. They excluded patients who died from causes unrelated to the primary endpoint, those who did not receive an anticoagulant or had incomplete data, and patients lost to follow-up, leaving 1,289 evaluable patients. During their 90-day follow-up, 10% of the patients had an ischemic event, a symptomatic intracranial hemorrhage, or an extracranial hemorrhage.
The study’s primary analysis showed no statistically significant difference in the incidence of recurrent ischemic events, symptomatic intracranial hemorrhage, or both based on when oral anticoagulant treatment began: 0-3 days, 4-14 days, or more than 14 days after the index stroke.
The investigators then subdivided patients into the subgroup that started treatment with a DOAC and the subgroup that started treatment with warfarin and also further subdivided the 4-14 day time window for starting treatment. Results of this analysis showed that patients who received a DOAC and began this treatment 7-10 days after their stroke had a 50% cut in their 90-day events compared with other patients, a difference that fell just short of statistical significance at P = .07. All the other combinations of oral anticoagulant and time of treatment initiation analyzed showed neutral effects that never came near statistical significance.
Secondary data analyses also showed that both patients with a history of a stroke prior to their index stroke and patients with ipsilateral atherosclerosis came close to having a statistically significant increased rate of a subsequent ischemic event during 90-day follow-up. Furthermore, women, patients with a history of hyperlipidemia, and patients who developed hemorrhagic transformation of their index stroke all had significantly increased rates of developing a symptomatic intracranial hemorrhage during 90-day follow-up. When the endpoint was limited to recurrent ischemic events only, patients who received a DOAC were 50% less likely to have an event than were patients treated with warfarin, a statistically significant difference.
Although starting a DOAC 7-10 days after the index stroke seems reasonable based on this analysis, the question needs a prospective, randomized study to create an appropriate evidence base, Dr. Yaghi said.
Dr. Yaghi disclosed a financial relationship with Medtronic. Dr. Simpkins had no disclosures.
SOURCE: Yaghi S et al. Stroke. 2020 Feb;51(suppl 1):A119.
LOS ANGELES – When a patient with atrial fibrillation (AFib) has a cardioembolic stroke, the best blood thinner to start may be a direct-acting oral anticoagulant (DOAC), possibly beginning 7-10 days after the index stroke, according to an analysis of 90-day, observational outcomes data from nearly 1,300 patients.
The analysis also suggested that the use of “bridging” anticoagulant treatment by injection before a patient with atrial fibrillation (AFib) starts a daily oral anticoagulant regimen following a cardioembolic stroke is not a good idea. Patients who received bridging anticoagulation had a nearly threefold higher rate of symptomatic intracranial hemorrhage than did patients who did not, and their bridging treatment failed to protect them from recurrent ischemic events, Shadi Yaghi, MD, said at the International Stroke Conference, sponsored by the American Heart Association. The bridging regimens delivered either heparin or low-molecular-weight heparin.
Based on the findings, “it seems reasonable to avoid bridging unless absolutely necessary, to initiate a DOAC unless it’s contraindicated, and to start the DOAC on day 7-10 following the stroke in most patients,” said Dr. Yaghi, a vascular neurologist and director of stroke research at NYU Langone Health in New York.
“It’s been hard to develop a broad guideline on when to start oral anticoagulation” after a cardioembolic stroke in AFib patients. The best time “depends on a lot of variables and how the patient responded to acute treatment,” commented Alexis Simpkins, MD, a vascular and stroke neurologist at the University of Florida in Gainesville. “You want to start treatment before the patient has another stroke, but not so soon that the treatment causes symptomatic hemorrhagic transformation.”
Dr. Yaghi’s suggestion, based on his findings, to start treatment for most patients with a DOAC 7-10 days after their index stroke “shows consistency” with the prevailing guideline recommendation from the AHA/American Stroke Association to start oral anticoagulation in this patient population 4-14 days after the index stroke (Stroke. 2018 March;49[3]:e46-e99), she noted.
A recent article reviewed the uncertainty about the best time to start oral anticoagulation in AFib patients after a cardioembolic stroke and the subtle differences that distinguish various international medical groups that, like the ASA, have made recommendations (Lancet Neurol. 2019 Jan 1;18[1]:117-26). According to this review, a major limitation of these various recommendations has been the lack of actual evidence collected from AFib patients who began receiving a DOAC shortly after a cardioembolic stroke, although the article added that several studies in progress are collecting these data.
The study reported by Dr. Yaghi pooled data collected from 2,084 recent AFib patients with a cardioembolic stroke treated at any of eight comprehensive U.S. stroke centers. They excluded patients who died from causes unrelated to the primary endpoint, those who did not receive an anticoagulant or had incomplete data, and patients lost to follow-up, leaving 1,289 evaluable patients. During their 90-day follow-up, 10% of the patients had an ischemic event, a symptomatic intracranial hemorrhage, or an extracranial hemorrhage.
The study’s primary analysis showed no statistically significant difference in the incidence of recurrent ischemic events, symptomatic intracranial hemorrhage, or both based on when oral anticoagulant treatment began: 0-3 days, 4-14 days, or more than 14 days after the index stroke.
The investigators then subdivided patients into the subgroup that started treatment with a DOAC and the subgroup that started treatment with warfarin and also further subdivided the 4-14 day time window for starting treatment. Results of this analysis showed that patients who received a DOAC and began this treatment 7-10 days after their stroke had a 50% cut in their 90-day events compared with other patients, a difference that fell just short of statistical significance at P = .07. All the other combinations of oral anticoagulant and time of treatment initiation analyzed showed neutral effects that never came near statistical significance.
Secondary data analyses also showed that both patients with a history of a stroke prior to their index stroke and patients with ipsilateral atherosclerosis came close to having a statistically significant increased rate of a subsequent ischemic event during 90-day follow-up. Furthermore, women, patients with a history of hyperlipidemia, and patients who developed hemorrhagic transformation of their index stroke all had significantly increased rates of developing a symptomatic intracranial hemorrhage during 90-day follow-up. When the endpoint was limited to recurrent ischemic events only, patients who received a DOAC were 50% less likely to have an event than were patients treated with warfarin, a statistically significant difference.
Although starting a DOAC 7-10 days after the index stroke seems reasonable based on this analysis, the question needs a prospective, randomized study to create an appropriate evidence base, Dr. Yaghi said.
Dr. Yaghi disclosed a financial relationship with Medtronic. Dr. Simpkins had no disclosures.
SOURCE: Yaghi S et al. Stroke. 2020 Feb;51(suppl 1):A119.
LOS ANGELES – When a patient with atrial fibrillation (AFib) has a cardioembolic stroke, the best blood thinner to start may be a direct-acting oral anticoagulant (DOAC), possibly beginning 7-10 days after the index stroke, according to an analysis of 90-day, observational outcomes data from nearly 1,300 patients.
The analysis also suggested that the use of “bridging” anticoagulant treatment by injection before a patient with atrial fibrillation (AFib) starts a daily oral anticoagulant regimen following a cardioembolic stroke is not a good idea. Patients who received bridging anticoagulation had a nearly threefold higher rate of symptomatic intracranial hemorrhage than did patients who did not, and their bridging treatment failed to protect them from recurrent ischemic events, Shadi Yaghi, MD, said at the International Stroke Conference, sponsored by the American Heart Association. The bridging regimens delivered either heparin or low-molecular-weight heparin.
Based on the findings, “it seems reasonable to avoid bridging unless absolutely necessary, to initiate a DOAC unless it’s contraindicated, and to start the DOAC on day 7-10 following the stroke in most patients,” said Dr. Yaghi, a vascular neurologist and director of stroke research at NYU Langone Health in New York.
“It’s been hard to develop a broad guideline on when to start oral anticoagulation” after a cardioembolic stroke in AFib patients. The best time “depends on a lot of variables and how the patient responded to acute treatment,” commented Alexis Simpkins, MD, a vascular and stroke neurologist at the University of Florida in Gainesville. “You want to start treatment before the patient has another stroke, but not so soon that the treatment causes symptomatic hemorrhagic transformation.”
Dr. Yaghi’s suggestion, based on his findings, to start treatment for most patients with a DOAC 7-10 days after their index stroke “shows consistency” with the prevailing guideline recommendation from the AHA/American Stroke Association to start oral anticoagulation in this patient population 4-14 days after the index stroke (Stroke. 2018 March;49[3]:e46-e99), she noted.
A recent article reviewed the uncertainty about the best time to start oral anticoagulation in AFib patients after a cardioembolic stroke and the subtle differences that distinguish various international medical groups that, like the ASA, have made recommendations (Lancet Neurol. 2019 Jan 1;18[1]:117-26). According to this review, a major limitation of these various recommendations has been the lack of actual evidence collected from AFib patients who began receiving a DOAC shortly after a cardioembolic stroke, although the article added that several studies in progress are collecting these data.
The study reported by Dr. Yaghi pooled data collected from 2,084 recent AFib patients with a cardioembolic stroke treated at any of eight comprehensive U.S. stroke centers. They excluded patients who died from causes unrelated to the primary endpoint, those who did not receive an anticoagulant or had incomplete data, and patients lost to follow-up, leaving 1,289 evaluable patients. During their 90-day follow-up, 10% of the patients had an ischemic event, a symptomatic intracranial hemorrhage, or an extracranial hemorrhage.
The study’s primary analysis showed no statistically significant difference in the incidence of recurrent ischemic events, symptomatic intracranial hemorrhage, or both based on when oral anticoagulant treatment began: 0-3 days, 4-14 days, or more than 14 days after the index stroke.
The investigators then subdivided patients into the subgroup that started treatment with a DOAC and the subgroup that started treatment with warfarin and also further subdivided the 4-14 day time window for starting treatment. Results of this analysis showed that patients who received a DOAC and began this treatment 7-10 days after their stroke had a 50% cut in their 90-day events compared with other patients, a difference that fell just short of statistical significance at P = .07. All the other combinations of oral anticoagulant and time of treatment initiation analyzed showed neutral effects that never came near statistical significance.
Secondary data analyses also showed that both patients with a history of a stroke prior to their index stroke and patients with ipsilateral atherosclerosis came close to having a statistically significant increased rate of a subsequent ischemic event during 90-day follow-up. Furthermore, women, patients with a history of hyperlipidemia, and patients who developed hemorrhagic transformation of their index stroke all had significantly increased rates of developing a symptomatic intracranial hemorrhage during 90-day follow-up. When the endpoint was limited to recurrent ischemic events only, patients who received a DOAC were 50% less likely to have an event than were patients treated with warfarin, a statistically significant difference.
Although starting a DOAC 7-10 days after the index stroke seems reasonable based on this analysis, the question needs a prospective, randomized study to create an appropriate evidence base, Dr. Yaghi said.
Dr. Yaghi disclosed a financial relationship with Medtronic. Dr. Simpkins had no disclosures.
SOURCE: Yaghi S et al. Stroke. 2020 Feb;51(suppl 1):A119.
REPORTING FROM ISC 2020
New strategies cut esophageal damage from AFib catheter ablation
NATIONAL HARBOR, MD. – Thermal injury of a patient’s esophagus during radiofrequency catheter ablation of atrial fibrillation is notorious as a relatively common and problematic complication of the procedure, but two new approaches showed promise for substantially cutting the risk of esophageal thermal injury and the potential for the most severe damage: perforation.
One of these innovations is intensive esophageal cooling with a commercially marketed, fluid-chilled catheter placed in a patient’s esophagus during radiofrequency catheter ablation that keeps the inner surface of the esophagus at 4°C. This approach cut the incidence of periprocedural episodes of endoscopically detected esophageal thermal injury from 20% among controls to 3% in patients who had esophageal cooling in a randomized study with 120 patients, Mark M. Gallagher, MD, said at the annual International AF Symposium. The same device can also maintain a temperature on the inner surface of the esophagus of 42 ° C in patients undergoing cryoablation of atrial fibrillation, noted Dr. Gallagher, a cardiac electrophysiologist at St. George’s University Hospitals in London.
A second approach to cutting esophageal damage focuses on modifying the energy delivery with a radiofrequency ablation method known as high-power short-duration (HPSD). As the name says, this strategy uses a relatively high level of radiofrequency energy, 50 watts in the reported experience, for the brief interval of about 7 seconds, ideally delivering an overall Ablation Index of at least 350 but below 360, said Thomas Deneke, MD, an electrophysiologist, professor, and cochief of cardiology at the Heart Center in Bad Neustadt, Germany.
Dr. Deneke and his associates in Bad Neustadt began using this HPSD approach in mid-2019, and by early 2020 they had data from 179 patients who underwent first-time catheter ablation of atrial fibrillation (AFib), all of whom had undergone routine esophageal endoscopy 1-3 days after their treatment. Eight patients (4%) showed evidence of endoscopically detected esophageal lesions (EDEL), including three patients (2%) with an actual esophageal ulcer, and one (0.6%) who developed a perforation that healed after 52 days, Dr. Deneke reported. An additional 55 patients underwent a redo catheter ablation procedure using the HPSD method during this period, and in that group follow-up endoscopy in all patients showed EDEL in two patients (4%). In contrast, during Jan. 2012–May 2019, the same German center treated 2,102 patients who had a first radiofrequency catheter ablation using convention energy levels and treatment times, which resulted in 291 patients having an EDEL (14%), including 94 (4%) with an ulcer, and six patients (0.3%) with an esophageal perforation, he said.
His center’s recent safety experience with HPSD radiofrequncy ablation, compared with the historical controls, suggests that this technique can produce a substantial reduction in esophageal thermal injury, but HPSD has not completely eliminated the risk and hence there is need for continued alertness for this potential complication Dr. Deneke concluded. The HPSD method is also limited by having “a very narrow window” between efficacy at an Ablation Index of 350 and safety when the index remains below 360, he added.
The randomized study that Dr. Gallagher ran at St. George’s followed an analysis he and his associates recently published that suggested efficacy using esophageal cooling in prior reports when the data combined in a meta-analysis (J Interv Card Electrophysiol. 2019 Nov 22. doi: 10.1007/s10840-019-00661-5). They also concluded that the clinical setting required a temperature control device with an enhanced capacity for rapid cooling, which prior studies had lacked. So they turned to a Food and Drug Administration–approved catheter designed for placement in the esophagus for the purpose of either whole-body cooling or warming.
The study randomized a total of 187 patients, but collected follow-up endoscopy at 5-7 days after the ablation procedure on 120 patients, of whom 60 received esophageal cooling and 60 did not. The types of ablations performed on patients in the two study arms were similar, and use of esophageal cooling had no impact on treatment duration or efficacy, either acute and longer term, Dr. Gallagher reported.
Cooling had a marked and statistically significant impact on endoscopically detected thermal injury. Although two patients in the group that underwent cooling had injuries, in one of these cases the injury involved a protocol violation: Radiofrequency ablation mistakenly occurred after the cooling device shut off, and it was during this period when the injury happened. In the second case of thermal injury, blinded scoring judged the injury as grade 2 in severity – an erosion of less than 5 mm – on a nine-item scale that ranged from zero to grade 6, the most severe level denoting a fistula. By contrast, among the 12 patients with thermal injury in the nonprotected subgroup, one patient had a grade 5a lesion denoting a deep ulcer, one had a 4b denoting a superficial ulcer with a clot, and four had a 4a lesion defined as a clean superficial ulcer.
“This is really effective. It’s the first study to show reduced damage without affecting ablation efficacy,” Dr. Gallagher said. He plans to now use this method of esophageal protection routinely for his AFib ablation patients who pay privately, and for patients insured under the national U.K. system once this coverage is approved. Dr. Deneke expressed his interest in also using this approach to esophageal protection, but noted that currently he did not have access to the cooling catheter that Dr. Gallagher used because of regulatory constraints.
The esophageal cooling study was sponsored by Attune Medical, which markets the cooling device. Dr. Gallagher has received research funding from Attune Medical, and has received honoraria as a speaker on behalf of Biosense Webster and Medtronic. Dr. Deneke has been a speaker on behalf of Abbott, Biosense Webster, Biotronik, and Boston Scientific, and his institution has received research funding from Biosense Webster and Securus/Boston Scientific.
NATIONAL HARBOR, MD. – Thermal injury of a patient’s esophagus during radiofrequency catheter ablation of atrial fibrillation is notorious as a relatively common and problematic complication of the procedure, but two new approaches showed promise for substantially cutting the risk of esophageal thermal injury and the potential for the most severe damage: perforation.
One of these innovations is intensive esophageal cooling with a commercially marketed, fluid-chilled catheter placed in a patient’s esophagus during radiofrequency catheter ablation that keeps the inner surface of the esophagus at 4°C. This approach cut the incidence of periprocedural episodes of endoscopically detected esophageal thermal injury from 20% among controls to 3% in patients who had esophageal cooling in a randomized study with 120 patients, Mark M. Gallagher, MD, said at the annual International AF Symposium. The same device can also maintain a temperature on the inner surface of the esophagus of 42 ° C in patients undergoing cryoablation of atrial fibrillation, noted Dr. Gallagher, a cardiac electrophysiologist at St. George’s University Hospitals in London.
A second approach to cutting esophageal damage focuses on modifying the energy delivery with a radiofrequency ablation method known as high-power short-duration (HPSD). As the name says, this strategy uses a relatively high level of radiofrequency energy, 50 watts in the reported experience, for the brief interval of about 7 seconds, ideally delivering an overall Ablation Index of at least 350 but below 360, said Thomas Deneke, MD, an electrophysiologist, professor, and cochief of cardiology at the Heart Center in Bad Neustadt, Germany.
Dr. Deneke and his associates in Bad Neustadt began using this HPSD approach in mid-2019, and by early 2020 they had data from 179 patients who underwent first-time catheter ablation of atrial fibrillation (AFib), all of whom had undergone routine esophageal endoscopy 1-3 days after their treatment. Eight patients (4%) showed evidence of endoscopically detected esophageal lesions (EDEL), including three patients (2%) with an actual esophageal ulcer, and one (0.6%) who developed a perforation that healed after 52 days, Dr. Deneke reported. An additional 55 patients underwent a redo catheter ablation procedure using the HPSD method during this period, and in that group follow-up endoscopy in all patients showed EDEL in two patients (4%). In contrast, during Jan. 2012–May 2019, the same German center treated 2,102 patients who had a first radiofrequency catheter ablation using convention energy levels and treatment times, which resulted in 291 patients having an EDEL (14%), including 94 (4%) with an ulcer, and six patients (0.3%) with an esophageal perforation, he said.
His center’s recent safety experience with HPSD radiofrequncy ablation, compared with the historical controls, suggests that this technique can produce a substantial reduction in esophageal thermal injury, but HPSD has not completely eliminated the risk and hence there is need for continued alertness for this potential complication Dr. Deneke concluded. The HPSD method is also limited by having “a very narrow window” between efficacy at an Ablation Index of 350 and safety when the index remains below 360, he added.
The randomized study that Dr. Gallagher ran at St. George’s followed an analysis he and his associates recently published that suggested efficacy using esophageal cooling in prior reports when the data combined in a meta-analysis (J Interv Card Electrophysiol. 2019 Nov 22. doi: 10.1007/s10840-019-00661-5). They also concluded that the clinical setting required a temperature control device with an enhanced capacity for rapid cooling, which prior studies had lacked. So they turned to a Food and Drug Administration–approved catheter designed for placement in the esophagus for the purpose of either whole-body cooling or warming.
The study randomized a total of 187 patients, but collected follow-up endoscopy at 5-7 days after the ablation procedure on 120 patients, of whom 60 received esophageal cooling and 60 did not. The types of ablations performed on patients in the two study arms were similar, and use of esophageal cooling had no impact on treatment duration or efficacy, either acute and longer term, Dr. Gallagher reported.
Cooling had a marked and statistically significant impact on endoscopically detected thermal injury. Although two patients in the group that underwent cooling had injuries, in one of these cases the injury involved a protocol violation: Radiofrequency ablation mistakenly occurred after the cooling device shut off, and it was during this period when the injury happened. In the second case of thermal injury, blinded scoring judged the injury as grade 2 in severity – an erosion of less than 5 mm – on a nine-item scale that ranged from zero to grade 6, the most severe level denoting a fistula. By contrast, among the 12 patients with thermal injury in the nonprotected subgroup, one patient had a grade 5a lesion denoting a deep ulcer, one had a 4b denoting a superficial ulcer with a clot, and four had a 4a lesion defined as a clean superficial ulcer.
“This is really effective. It’s the first study to show reduced damage without affecting ablation efficacy,” Dr. Gallagher said. He plans to now use this method of esophageal protection routinely for his AFib ablation patients who pay privately, and for patients insured under the national U.K. system once this coverage is approved. Dr. Deneke expressed his interest in also using this approach to esophageal protection, but noted that currently he did not have access to the cooling catheter that Dr. Gallagher used because of regulatory constraints.
The esophageal cooling study was sponsored by Attune Medical, which markets the cooling device. Dr. Gallagher has received research funding from Attune Medical, and has received honoraria as a speaker on behalf of Biosense Webster and Medtronic. Dr. Deneke has been a speaker on behalf of Abbott, Biosense Webster, Biotronik, and Boston Scientific, and his institution has received research funding from Biosense Webster and Securus/Boston Scientific.
NATIONAL HARBOR, MD. – Thermal injury of a patient’s esophagus during radiofrequency catheter ablation of atrial fibrillation is notorious as a relatively common and problematic complication of the procedure, but two new approaches showed promise for substantially cutting the risk of esophageal thermal injury and the potential for the most severe damage: perforation.
One of these innovations is intensive esophageal cooling with a commercially marketed, fluid-chilled catheter placed in a patient’s esophagus during radiofrequency catheter ablation that keeps the inner surface of the esophagus at 4°C. This approach cut the incidence of periprocedural episodes of endoscopically detected esophageal thermal injury from 20% among controls to 3% in patients who had esophageal cooling in a randomized study with 120 patients, Mark M. Gallagher, MD, said at the annual International AF Symposium. The same device can also maintain a temperature on the inner surface of the esophagus of 42 ° C in patients undergoing cryoablation of atrial fibrillation, noted Dr. Gallagher, a cardiac electrophysiologist at St. George’s University Hospitals in London.
A second approach to cutting esophageal damage focuses on modifying the energy delivery with a radiofrequency ablation method known as high-power short-duration (HPSD). As the name says, this strategy uses a relatively high level of radiofrequency energy, 50 watts in the reported experience, for the brief interval of about 7 seconds, ideally delivering an overall Ablation Index of at least 350 but below 360, said Thomas Deneke, MD, an electrophysiologist, professor, and cochief of cardiology at the Heart Center in Bad Neustadt, Germany.
Dr. Deneke and his associates in Bad Neustadt began using this HPSD approach in mid-2019, and by early 2020 they had data from 179 patients who underwent first-time catheter ablation of atrial fibrillation (AFib), all of whom had undergone routine esophageal endoscopy 1-3 days after their treatment. Eight patients (4%) showed evidence of endoscopically detected esophageal lesions (EDEL), including three patients (2%) with an actual esophageal ulcer, and one (0.6%) who developed a perforation that healed after 52 days, Dr. Deneke reported. An additional 55 patients underwent a redo catheter ablation procedure using the HPSD method during this period, and in that group follow-up endoscopy in all patients showed EDEL in two patients (4%). In contrast, during Jan. 2012–May 2019, the same German center treated 2,102 patients who had a first radiofrequency catheter ablation using convention energy levels and treatment times, which resulted in 291 patients having an EDEL (14%), including 94 (4%) with an ulcer, and six patients (0.3%) with an esophageal perforation, he said.
His center’s recent safety experience with HPSD radiofrequncy ablation, compared with the historical controls, suggests that this technique can produce a substantial reduction in esophageal thermal injury, but HPSD has not completely eliminated the risk and hence there is need for continued alertness for this potential complication Dr. Deneke concluded. The HPSD method is also limited by having “a very narrow window” between efficacy at an Ablation Index of 350 and safety when the index remains below 360, he added.
The randomized study that Dr. Gallagher ran at St. George’s followed an analysis he and his associates recently published that suggested efficacy using esophageal cooling in prior reports when the data combined in a meta-analysis (J Interv Card Electrophysiol. 2019 Nov 22. doi: 10.1007/s10840-019-00661-5). They also concluded that the clinical setting required a temperature control device with an enhanced capacity for rapid cooling, which prior studies had lacked. So they turned to a Food and Drug Administration–approved catheter designed for placement in the esophagus for the purpose of either whole-body cooling or warming.
The study randomized a total of 187 patients, but collected follow-up endoscopy at 5-7 days after the ablation procedure on 120 patients, of whom 60 received esophageal cooling and 60 did not. The types of ablations performed on patients in the two study arms were similar, and use of esophageal cooling had no impact on treatment duration or efficacy, either acute and longer term, Dr. Gallagher reported.
Cooling had a marked and statistically significant impact on endoscopically detected thermal injury. Although two patients in the group that underwent cooling had injuries, in one of these cases the injury involved a protocol violation: Radiofrequency ablation mistakenly occurred after the cooling device shut off, and it was during this period when the injury happened. In the second case of thermal injury, blinded scoring judged the injury as grade 2 in severity – an erosion of less than 5 mm – on a nine-item scale that ranged from zero to grade 6, the most severe level denoting a fistula. By contrast, among the 12 patients with thermal injury in the nonprotected subgroup, one patient had a grade 5a lesion denoting a deep ulcer, one had a 4b denoting a superficial ulcer with a clot, and four had a 4a lesion defined as a clean superficial ulcer.
“This is really effective. It’s the first study to show reduced damage without affecting ablation efficacy,” Dr. Gallagher said. He plans to now use this method of esophageal protection routinely for his AFib ablation patients who pay privately, and for patients insured under the national U.K. system once this coverage is approved. Dr. Deneke expressed his interest in also using this approach to esophageal protection, but noted that currently he did not have access to the cooling catheter that Dr. Gallagher used because of regulatory constraints.
The esophageal cooling study was sponsored by Attune Medical, which markets the cooling device. Dr. Gallagher has received research funding from Attune Medical, and has received honoraria as a speaker on behalf of Biosense Webster and Medtronic. Dr. Deneke has been a speaker on behalf of Abbott, Biosense Webster, Biotronik, and Boston Scientific, and his institution has received research funding from Biosense Webster and Securus/Boston Scientific.
THE AF SYMPOSIUM 2020
AI algorithm finds diagnostic AFib signatures in normal ECGs
NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.
Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.
This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.
The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.
The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.
It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.
While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.
The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).
The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.
NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.
Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.
This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.
The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.
The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.
It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.
While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.
The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).
The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.
NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.
Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.
This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.
The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.
The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.
It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.
While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.
The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).
The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.
THE AF SYMPOSIUM 2020
Pulsed field catheter ablation shows huge clinical promise for AFib
NATIONAL HARBOR, MD. – Cardiac electrophysiologists have reported using pulsed field ablation, a new power source for catheter ablation of atrial fibrillation, on fewer than 150 patients worldwide in initial clinical studies, but its performance so far and the promise it carries for substantially improving the safety and efficacy of catheter ablation has convinced many experts that it represents the future for this intervention.
“I’m very excited about PFA [pulsed field ablation]. It may make everything else obsolete,” Andrea Natale, MD, said at the annual International AF Symposium. “We need to see more efficacy data, but just for safety alone there is no reason to use anything else,” commented Dr. Natale, executive medical director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin,Tex.
“The main issue is safety, and if PFA lives up to its promise, then [using it preferentially] is not a difficult decision,” commented Francis E. Marchlinski, MD, professor of medicine and director of electrophysiology at the University of Pennsylvania.
“The only question is whether it has good long-term efficacy” because so far no patients have been followed for longer than about a year after PFA treatment, noted Moussa Mansour, MD, director of the cardiac electrophysiology laboratory at Massachusetts General Hospital in Boston. “If that piece turns out to be true, then I think it will be a winner.”
Vivek Y. Reddy, MD, one of the few investigators to have already collaborated on clinical studies that used PFA to catheter ablate both in patients with paroxysmal and, more recently, persistent atrial fibrillation (AFib), put it this way: “I’m 99% sure” PFA will be the energy of choice in the near future for AFib catheter ablation. The 1% of uncertainty “is only because of what might be unknown, something we’re not expecting,” said Dr. Reddy, professor of medicine and director of the cardiac arrhythmia service at Mount Sinai Medical Center in New York.
He and his associates at a center in Prague and at a second site in Bordeaux, France, reported their collective experience in 2019 regarding use of PFA on 81 patients with symptomatic, paroxysmal AFib who had not responded to at least one antiarrhythmic drug (J Am Coll Cardiol. 2019 Jul;74[3]:315-26). During a session on PFA at the symposium, Pierre Jaïs, MD, a cardiac electrophysiologist and professor of cardiology at the University of Bordeaux, updated this experience to now include 113 patients treated by the end of 2019 at the same two centers plus now an added third site, an experience accumulated by a total of five operators. Fifty-one patients have now been followed for at least a year, with no “unexpected” safety events, said Dr. Jaïs, The most recent 88 patients underwent PFA without general anesthesia. The ablation technique has undergone several refinements during this experience, and with use of the most recent, biphasic protocol that’s so far treated 26 patients, 24 (92%) of the treated patients had no reconnected AFib circuits in their atrial tissue when they underwent remapping 3 months after their procedure.
Magnetic resonance imaging of the left atria of these patients after pulmonary vein isolation with PFA showed a uniquely homogeneous and continuous lesion that functionally isolated each vein from surrounding atrial tissue and denoted a more uniform and complete ablation, Dr. Jaïs noted. “I have never seen [an ablation] as homogeneous.” The Magnetic resonance pictures also showed that the esophagus in each treated patient remained completely undamaged. “Esophageal sparing is systematically observed,” along with phrenic nerve sparing that’s in notable contrast with what’s seen with conventional energy sources, he said. The images also indicated that edema was substantially reduced compared with both radiofrequency and cryoablation, while mechanical function of treated left atria has consistently been “well preserved.”
“For the first time, we can use extra power to ensure durable lesions without compromising safety,” Dr. Jaïs concluded. PFA appears to put AFib ablation “on the verge of a totally new era.”
The less extensive and briefer experience in patients with persistent AFib has been completely consistent. This included 25 patients who had not responded to at least one antiarrhythmic drug treated by either of two operators, one in Prague and the other in Split, Croatia. All 25 patients who underwent pulmonary vein isolation had the procedure successfully completed as assessed with acute mapping of arrhythmia circuits after ablation, and the 24 of these patients who also underwent posterior wall ablation with the PFA device all had a successful acute result according to mapping, Dr. Reddy reported. No patient had an adverse event. PFA treatments were relatively fast, with an average procedure time in this series of 132 minutes. Repeat mapping 3 months after treatment is still pending.
At the heart of PFA’s safety is its “myocardial selectivity” which has so far kept PFA from causing any esophageal or phrenic nerve injuries, two potential complications of conventional AFib catheter ablation with use of either radiofrequency or cryo energy. Dr. Reddy was quick to highlight that there is no absolute selectivity for myocardium. “If you create a big enough field, it will electroporate everything, but the margin [between safety and damage] seems wide enough to take advantage” of focally damaging myocardial tissue in the left atrium to disrupt arrhythmia circuits while sparing adjacent tissue. Irreversible electroporation is the means by which PFA destroys targets cells while leaving other tissue unscathed, and a precisely adjusted PFA signal can focus its lethal effect exclusively on myocardial cells, a feature of PFA that Dr. Reddy called “lucky.”
The pulsed field ablation studies have been sponsored by Farapulse, the company developing this device, which in May 2019 received breakthrough designation for priority review from the Food and Drug Administration.
Dr. Reddy and Dr. Jaïs are both consultants to and shareholders in Farapulse. Dr. Natale has received honoraria from or has been a consultant to Biotronik, Janssen, Medtronic, and St. Jude. Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biotronik, and Medtronic. Dr. Mansour has been a consultant for Abbott and Medtronic, has an equity interest or stock options in NewPace and EPD Solutions, and has received research grants from Abbott, Boehringer Ingelheim, Pfizer, and Sentre Heart. In addition, all sources have received consulting fees, honoraria, and/or research grants from Biosense Webster and Boston Scientific.
NATIONAL HARBOR, MD. – Cardiac electrophysiologists have reported using pulsed field ablation, a new power source for catheter ablation of atrial fibrillation, on fewer than 150 patients worldwide in initial clinical studies, but its performance so far and the promise it carries for substantially improving the safety and efficacy of catheter ablation has convinced many experts that it represents the future for this intervention.
“I’m very excited about PFA [pulsed field ablation]. It may make everything else obsolete,” Andrea Natale, MD, said at the annual International AF Symposium. “We need to see more efficacy data, but just for safety alone there is no reason to use anything else,” commented Dr. Natale, executive medical director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin,Tex.
“The main issue is safety, and if PFA lives up to its promise, then [using it preferentially] is not a difficult decision,” commented Francis E. Marchlinski, MD, professor of medicine and director of electrophysiology at the University of Pennsylvania.
“The only question is whether it has good long-term efficacy” because so far no patients have been followed for longer than about a year after PFA treatment, noted Moussa Mansour, MD, director of the cardiac electrophysiology laboratory at Massachusetts General Hospital in Boston. “If that piece turns out to be true, then I think it will be a winner.”
Vivek Y. Reddy, MD, one of the few investigators to have already collaborated on clinical studies that used PFA to catheter ablate both in patients with paroxysmal and, more recently, persistent atrial fibrillation (AFib), put it this way: “I’m 99% sure” PFA will be the energy of choice in the near future for AFib catheter ablation. The 1% of uncertainty “is only because of what might be unknown, something we’re not expecting,” said Dr. Reddy, professor of medicine and director of the cardiac arrhythmia service at Mount Sinai Medical Center in New York.
He and his associates at a center in Prague and at a second site in Bordeaux, France, reported their collective experience in 2019 regarding use of PFA on 81 patients with symptomatic, paroxysmal AFib who had not responded to at least one antiarrhythmic drug (J Am Coll Cardiol. 2019 Jul;74[3]:315-26). During a session on PFA at the symposium, Pierre Jaïs, MD, a cardiac electrophysiologist and professor of cardiology at the University of Bordeaux, updated this experience to now include 113 patients treated by the end of 2019 at the same two centers plus now an added third site, an experience accumulated by a total of five operators. Fifty-one patients have now been followed for at least a year, with no “unexpected” safety events, said Dr. Jaïs, The most recent 88 patients underwent PFA without general anesthesia. The ablation technique has undergone several refinements during this experience, and with use of the most recent, biphasic protocol that’s so far treated 26 patients, 24 (92%) of the treated patients had no reconnected AFib circuits in their atrial tissue when they underwent remapping 3 months after their procedure.
Magnetic resonance imaging of the left atria of these patients after pulmonary vein isolation with PFA showed a uniquely homogeneous and continuous lesion that functionally isolated each vein from surrounding atrial tissue and denoted a more uniform and complete ablation, Dr. Jaïs noted. “I have never seen [an ablation] as homogeneous.” The Magnetic resonance pictures also showed that the esophagus in each treated patient remained completely undamaged. “Esophageal sparing is systematically observed,” along with phrenic nerve sparing that’s in notable contrast with what’s seen with conventional energy sources, he said. The images also indicated that edema was substantially reduced compared with both radiofrequency and cryoablation, while mechanical function of treated left atria has consistently been “well preserved.”
“For the first time, we can use extra power to ensure durable lesions without compromising safety,” Dr. Jaïs concluded. PFA appears to put AFib ablation “on the verge of a totally new era.”
The less extensive and briefer experience in patients with persistent AFib has been completely consistent. This included 25 patients who had not responded to at least one antiarrhythmic drug treated by either of two operators, one in Prague and the other in Split, Croatia. All 25 patients who underwent pulmonary vein isolation had the procedure successfully completed as assessed with acute mapping of arrhythmia circuits after ablation, and the 24 of these patients who also underwent posterior wall ablation with the PFA device all had a successful acute result according to mapping, Dr. Reddy reported. No patient had an adverse event. PFA treatments were relatively fast, with an average procedure time in this series of 132 minutes. Repeat mapping 3 months after treatment is still pending.
At the heart of PFA’s safety is its “myocardial selectivity” which has so far kept PFA from causing any esophageal or phrenic nerve injuries, two potential complications of conventional AFib catheter ablation with use of either radiofrequency or cryo energy. Dr. Reddy was quick to highlight that there is no absolute selectivity for myocardium. “If you create a big enough field, it will electroporate everything, but the margin [between safety and damage] seems wide enough to take advantage” of focally damaging myocardial tissue in the left atrium to disrupt arrhythmia circuits while sparing adjacent tissue. Irreversible electroporation is the means by which PFA destroys targets cells while leaving other tissue unscathed, and a precisely adjusted PFA signal can focus its lethal effect exclusively on myocardial cells, a feature of PFA that Dr. Reddy called “lucky.”
The pulsed field ablation studies have been sponsored by Farapulse, the company developing this device, which in May 2019 received breakthrough designation for priority review from the Food and Drug Administration.
Dr. Reddy and Dr. Jaïs are both consultants to and shareholders in Farapulse. Dr. Natale has received honoraria from or has been a consultant to Biotronik, Janssen, Medtronic, and St. Jude. Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biotronik, and Medtronic. Dr. Mansour has been a consultant for Abbott and Medtronic, has an equity interest or stock options in NewPace and EPD Solutions, and has received research grants from Abbott, Boehringer Ingelheim, Pfizer, and Sentre Heart. In addition, all sources have received consulting fees, honoraria, and/or research grants from Biosense Webster and Boston Scientific.
NATIONAL HARBOR, MD. – Cardiac electrophysiologists have reported using pulsed field ablation, a new power source for catheter ablation of atrial fibrillation, on fewer than 150 patients worldwide in initial clinical studies, but its performance so far and the promise it carries for substantially improving the safety and efficacy of catheter ablation has convinced many experts that it represents the future for this intervention.
“I’m very excited about PFA [pulsed field ablation]. It may make everything else obsolete,” Andrea Natale, MD, said at the annual International AF Symposium. “We need to see more efficacy data, but just for safety alone there is no reason to use anything else,” commented Dr. Natale, executive medical director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin,Tex.
“The main issue is safety, and if PFA lives up to its promise, then [using it preferentially] is not a difficult decision,” commented Francis E. Marchlinski, MD, professor of medicine and director of electrophysiology at the University of Pennsylvania.
“The only question is whether it has good long-term efficacy” because so far no patients have been followed for longer than about a year after PFA treatment, noted Moussa Mansour, MD, director of the cardiac electrophysiology laboratory at Massachusetts General Hospital in Boston. “If that piece turns out to be true, then I think it will be a winner.”
Vivek Y. Reddy, MD, one of the few investigators to have already collaborated on clinical studies that used PFA to catheter ablate both in patients with paroxysmal and, more recently, persistent atrial fibrillation (AFib), put it this way: “I’m 99% sure” PFA will be the energy of choice in the near future for AFib catheter ablation. The 1% of uncertainty “is only because of what might be unknown, something we’re not expecting,” said Dr. Reddy, professor of medicine and director of the cardiac arrhythmia service at Mount Sinai Medical Center in New York.
He and his associates at a center in Prague and at a second site in Bordeaux, France, reported their collective experience in 2019 regarding use of PFA on 81 patients with symptomatic, paroxysmal AFib who had not responded to at least one antiarrhythmic drug (J Am Coll Cardiol. 2019 Jul;74[3]:315-26). During a session on PFA at the symposium, Pierre Jaïs, MD, a cardiac electrophysiologist and professor of cardiology at the University of Bordeaux, updated this experience to now include 113 patients treated by the end of 2019 at the same two centers plus now an added third site, an experience accumulated by a total of five operators. Fifty-one patients have now been followed for at least a year, with no “unexpected” safety events, said Dr. Jaïs, The most recent 88 patients underwent PFA without general anesthesia. The ablation technique has undergone several refinements during this experience, and with use of the most recent, biphasic protocol that’s so far treated 26 patients, 24 (92%) of the treated patients had no reconnected AFib circuits in their atrial tissue when they underwent remapping 3 months after their procedure.
Magnetic resonance imaging of the left atria of these patients after pulmonary vein isolation with PFA showed a uniquely homogeneous and continuous lesion that functionally isolated each vein from surrounding atrial tissue and denoted a more uniform and complete ablation, Dr. Jaïs noted. “I have never seen [an ablation] as homogeneous.” The Magnetic resonance pictures also showed that the esophagus in each treated patient remained completely undamaged. “Esophageal sparing is systematically observed,” along with phrenic nerve sparing that’s in notable contrast with what’s seen with conventional energy sources, he said. The images also indicated that edema was substantially reduced compared with both radiofrequency and cryoablation, while mechanical function of treated left atria has consistently been “well preserved.”
“For the first time, we can use extra power to ensure durable lesions without compromising safety,” Dr. Jaïs concluded. PFA appears to put AFib ablation “on the verge of a totally new era.”
The less extensive and briefer experience in patients with persistent AFib has been completely consistent. This included 25 patients who had not responded to at least one antiarrhythmic drug treated by either of two operators, one in Prague and the other in Split, Croatia. All 25 patients who underwent pulmonary vein isolation had the procedure successfully completed as assessed with acute mapping of arrhythmia circuits after ablation, and the 24 of these patients who also underwent posterior wall ablation with the PFA device all had a successful acute result according to mapping, Dr. Reddy reported. No patient had an adverse event. PFA treatments were relatively fast, with an average procedure time in this series of 132 minutes. Repeat mapping 3 months after treatment is still pending.
At the heart of PFA’s safety is its “myocardial selectivity” which has so far kept PFA from causing any esophageal or phrenic nerve injuries, two potential complications of conventional AFib catheter ablation with use of either radiofrequency or cryo energy. Dr. Reddy was quick to highlight that there is no absolute selectivity for myocardium. “If you create a big enough field, it will electroporate everything, but the margin [between safety and damage] seems wide enough to take advantage” of focally damaging myocardial tissue in the left atrium to disrupt arrhythmia circuits while sparing adjacent tissue. Irreversible electroporation is the means by which PFA destroys targets cells while leaving other tissue unscathed, and a precisely adjusted PFA signal can focus its lethal effect exclusively on myocardial cells, a feature of PFA that Dr. Reddy called “lucky.”
The pulsed field ablation studies have been sponsored by Farapulse, the company developing this device, which in May 2019 received breakthrough designation for priority review from the Food and Drug Administration.
Dr. Reddy and Dr. Jaïs are both consultants to and shareholders in Farapulse. Dr. Natale has received honoraria from or has been a consultant to Biotronik, Janssen, Medtronic, and St. Jude. Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biotronik, and Medtronic. Dr. Mansour has been a consultant for Abbott and Medtronic, has an equity interest or stock options in NewPace and EPD Solutions, and has received research grants from Abbott, Boehringer Ingelheim, Pfizer, and Sentre Heart. In addition, all sources have received consulting fees, honoraria, and/or research grants from Biosense Webster and Boston Scientific.
EXPERT ANALYSIS FROM THE AF SYMPOSIUM 2020
‘A glimmer of hope’ for stroke/mortality benefit with AFib catheter ablation
SNOWMASS, COLO. – stroke, major bleeding, or cardiac arrest, compared with rhythm and/or rate control drugs in a propensity score–weighted, retrospective, observational study.
Findings of the investigation, which included more than 183,000 real-world patients in routine clinical practice, were reported by Peter S. Noseworthy, MD, during the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The results breathe new life into the controversy created by the previously reported CABANA trial (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation), a 10-country study in which 2,204 patients with atrial fibrillation (AFib) were randomized to catheter ablation or antiarrhythmic and/or rhythm control medications and followed for a mean of about 4 years. CABANA yielded a negative result (JAMA. 2019 Apr 2;321[13]:1261-74), with the prespecified intent-to-treat analysis indicating no significant between-group difference in the primary composite endpoint – the very same one that was positive in the large observational study.
However, CABANA was marred by major problems arising from protocol deviations: Nearly 28% of patients assigned to medical therapy crossed over to catheter ablation, typically because their antiarrhythmic drugs failed, and 10% of patients randomized to catheter ablation never got it. This muddies the waters when trying to identify a true stroke/mortality benefit for catheter ablation, if indeed any such benefit was actually present.
Here’s where the controversy arose: While CABANA must be called a negative trial based upon the disappointing results of the intent-to-treat analysis, a prespecified post hoc analysis of patients as actually treated showed a statistically significant 27% relative risk reduction for the primary composite endpoint in the catheter ablation group. That’s strikingly similar to the 30% relative risk reduction for catheter ablation seen in the huge observational study, where the CABANA-type primary outcome occurred in 22.5% of the medically managed patients and 16.8% of those who underwent catheter ablation, noted Dr. Noseworthy, professor of medicine and director of heart rhythm and physiology at the Mayo Clinic in Rochester, Minn.
He ought to know: He was both an investigator in CABANA and first author of the published observational study (Eur Heart J. 2019 Apr 21;40[16]:1257-64).
In the observational study, Dr. Noseworthy and coinvestigators utilized a huge U.S. administrative health claims database in order to identify a nationally representative group of 183,760 AFib patients, 12,032 of whom were treated with catheter ablation and the rest with antiarrhythmic and/or rhythm control drugs during the same years the CABANA trial was enrolling patients. The two groups were balanced using propensity score weighting to adjust for baseline differences in 90 variables.
The investigators sought to learn if the CABANA study population was representative of real-world AFib patients, and whether the observational experience could help resolve the CABANA controversy. It turned out that most AFib patients seen in daily clinical practice were CABANA like; that is, 74% of them would have been eligible for the clinical trial because they were symptomatic, over age 65, or younger than 65 with at least one CHADS2 stroke risk factor. About 22% of the large real-world sample would have been excluded from CABANA because they’d failed on amiodarone and other antiarrhythmic agents or had previously undergone ablation. About 4% of patients failed to meet the CABANA inclusion criteria.
The risk reduction for the composite endpoint associated with catheter ablation in the large retrospective study was greatest in the CABANA-like patients, at 30%. It was less robust but still statistically significant at 15% in patients who met at least one of the exclusion criteria for the trial.
The sheer size of this study provides greater statistical power than in CABANA. Of course, a nonrandomized, propensity score–based comparison such as this is always susceptible to confounding, even after adjustment for 90 variables. But the observational study does offer “a glimmer of hope” that catheter ablation, done in the right patients, might confer a stroke risk reduction and mortality benefit, he said.
The 33% relative risk reduction in the small group of real-world patients who failed to meet the CABANA inclusion criteria, while numerically impressive, wasn’t close to statistical significance, probably because event rates in that population were so low.
“Even if you could reduce stroke risk with ablation in that low-risk group, it would be a very inefficient way to reduce the population burden of stroke,” Dr. Noseworthy observed.
Putting together the results of CABANA and the large observational study to sum up his view of where catheter ablation for AF[ib] stands today, Dr. Noseworthy commented, “Ablation is reasonable for symptom control in many patients, basically anyone who is either breaking through on drugs or doesn’t want to take the drugs and is highly symptomatic. And there may be a small stroke and/or mortality benefit for people who are in the sweet spot – and those are people who look a lot like the patients enrolled in CABANA.”
Patients who met the exclusion criteria for CABANA are too advanced in their AFib to be likely to derive a stroke or mortality benefit from catheter ablation. “It’s very hard to move the needle in these patients with either a drug or catheter ablation approach. I wouldn’t try to reduce the risk of stroke here with an expensive and invasive procedure,” the electrophysiologist concluded.
He reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – stroke, major bleeding, or cardiac arrest, compared with rhythm and/or rate control drugs in a propensity score–weighted, retrospective, observational study.
Findings of the investigation, which included more than 183,000 real-world patients in routine clinical practice, were reported by Peter S. Noseworthy, MD, during the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The results breathe new life into the controversy created by the previously reported CABANA trial (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation), a 10-country study in which 2,204 patients with atrial fibrillation (AFib) were randomized to catheter ablation or antiarrhythmic and/or rhythm control medications and followed for a mean of about 4 years. CABANA yielded a negative result (JAMA. 2019 Apr 2;321[13]:1261-74), with the prespecified intent-to-treat analysis indicating no significant between-group difference in the primary composite endpoint – the very same one that was positive in the large observational study.
However, CABANA was marred by major problems arising from protocol deviations: Nearly 28% of patients assigned to medical therapy crossed over to catheter ablation, typically because their antiarrhythmic drugs failed, and 10% of patients randomized to catheter ablation never got it. This muddies the waters when trying to identify a true stroke/mortality benefit for catheter ablation, if indeed any such benefit was actually present.
Here’s where the controversy arose: While CABANA must be called a negative trial based upon the disappointing results of the intent-to-treat analysis, a prespecified post hoc analysis of patients as actually treated showed a statistically significant 27% relative risk reduction for the primary composite endpoint in the catheter ablation group. That’s strikingly similar to the 30% relative risk reduction for catheter ablation seen in the huge observational study, where the CABANA-type primary outcome occurred in 22.5% of the medically managed patients and 16.8% of those who underwent catheter ablation, noted Dr. Noseworthy, professor of medicine and director of heart rhythm and physiology at the Mayo Clinic in Rochester, Minn.
He ought to know: He was both an investigator in CABANA and first author of the published observational study (Eur Heart J. 2019 Apr 21;40[16]:1257-64).
In the observational study, Dr. Noseworthy and coinvestigators utilized a huge U.S. administrative health claims database in order to identify a nationally representative group of 183,760 AFib patients, 12,032 of whom were treated with catheter ablation and the rest with antiarrhythmic and/or rhythm control drugs during the same years the CABANA trial was enrolling patients. The two groups were balanced using propensity score weighting to adjust for baseline differences in 90 variables.
The investigators sought to learn if the CABANA study population was representative of real-world AFib patients, and whether the observational experience could help resolve the CABANA controversy. It turned out that most AFib patients seen in daily clinical practice were CABANA like; that is, 74% of them would have been eligible for the clinical trial because they were symptomatic, over age 65, or younger than 65 with at least one CHADS2 stroke risk factor. About 22% of the large real-world sample would have been excluded from CABANA because they’d failed on amiodarone and other antiarrhythmic agents or had previously undergone ablation. About 4% of patients failed to meet the CABANA inclusion criteria.
The risk reduction for the composite endpoint associated with catheter ablation in the large retrospective study was greatest in the CABANA-like patients, at 30%. It was less robust but still statistically significant at 15% in patients who met at least one of the exclusion criteria for the trial.
The sheer size of this study provides greater statistical power than in CABANA. Of course, a nonrandomized, propensity score–based comparison such as this is always susceptible to confounding, even after adjustment for 90 variables. But the observational study does offer “a glimmer of hope” that catheter ablation, done in the right patients, might confer a stroke risk reduction and mortality benefit, he said.
The 33% relative risk reduction in the small group of real-world patients who failed to meet the CABANA inclusion criteria, while numerically impressive, wasn’t close to statistical significance, probably because event rates in that population were so low.
“Even if you could reduce stroke risk with ablation in that low-risk group, it would be a very inefficient way to reduce the population burden of stroke,” Dr. Noseworthy observed.
Putting together the results of CABANA and the large observational study to sum up his view of where catheter ablation for AF[ib] stands today, Dr. Noseworthy commented, “Ablation is reasonable for symptom control in many patients, basically anyone who is either breaking through on drugs or doesn’t want to take the drugs and is highly symptomatic. And there may be a small stroke and/or mortality benefit for people who are in the sweet spot – and those are people who look a lot like the patients enrolled in CABANA.”
Patients who met the exclusion criteria for CABANA are too advanced in their AFib to be likely to derive a stroke or mortality benefit from catheter ablation. “It’s very hard to move the needle in these patients with either a drug or catheter ablation approach. I wouldn’t try to reduce the risk of stroke here with an expensive and invasive procedure,” the electrophysiologist concluded.
He reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – stroke, major bleeding, or cardiac arrest, compared with rhythm and/or rate control drugs in a propensity score–weighted, retrospective, observational study.
Findings of the investigation, which included more than 183,000 real-world patients in routine clinical practice, were reported by Peter S. Noseworthy, MD, during the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The results breathe new life into the controversy created by the previously reported CABANA trial (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation), a 10-country study in which 2,204 patients with atrial fibrillation (AFib) were randomized to catheter ablation or antiarrhythmic and/or rhythm control medications and followed for a mean of about 4 years. CABANA yielded a negative result (JAMA. 2019 Apr 2;321[13]:1261-74), with the prespecified intent-to-treat analysis indicating no significant between-group difference in the primary composite endpoint – the very same one that was positive in the large observational study.
However, CABANA was marred by major problems arising from protocol deviations: Nearly 28% of patients assigned to medical therapy crossed over to catheter ablation, typically because their antiarrhythmic drugs failed, and 10% of patients randomized to catheter ablation never got it. This muddies the waters when trying to identify a true stroke/mortality benefit for catheter ablation, if indeed any such benefit was actually present.
Here’s where the controversy arose: While CABANA must be called a negative trial based upon the disappointing results of the intent-to-treat analysis, a prespecified post hoc analysis of patients as actually treated showed a statistically significant 27% relative risk reduction for the primary composite endpoint in the catheter ablation group. That’s strikingly similar to the 30% relative risk reduction for catheter ablation seen in the huge observational study, where the CABANA-type primary outcome occurred in 22.5% of the medically managed patients and 16.8% of those who underwent catheter ablation, noted Dr. Noseworthy, professor of medicine and director of heart rhythm and physiology at the Mayo Clinic in Rochester, Minn.
He ought to know: He was both an investigator in CABANA and first author of the published observational study (Eur Heart J. 2019 Apr 21;40[16]:1257-64).
In the observational study, Dr. Noseworthy and coinvestigators utilized a huge U.S. administrative health claims database in order to identify a nationally representative group of 183,760 AFib patients, 12,032 of whom were treated with catheter ablation and the rest with antiarrhythmic and/or rhythm control drugs during the same years the CABANA trial was enrolling patients. The two groups were balanced using propensity score weighting to adjust for baseline differences in 90 variables.
The investigators sought to learn if the CABANA study population was representative of real-world AFib patients, and whether the observational experience could help resolve the CABANA controversy. It turned out that most AFib patients seen in daily clinical practice were CABANA like; that is, 74% of them would have been eligible for the clinical trial because they were symptomatic, over age 65, or younger than 65 with at least one CHADS2 stroke risk factor. About 22% of the large real-world sample would have been excluded from CABANA because they’d failed on amiodarone and other antiarrhythmic agents or had previously undergone ablation. About 4% of patients failed to meet the CABANA inclusion criteria.
The risk reduction for the composite endpoint associated with catheter ablation in the large retrospective study was greatest in the CABANA-like patients, at 30%. It was less robust but still statistically significant at 15% in patients who met at least one of the exclusion criteria for the trial.
The sheer size of this study provides greater statistical power than in CABANA. Of course, a nonrandomized, propensity score–based comparison such as this is always susceptible to confounding, even after adjustment for 90 variables. But the observational study does offer “a glimmer of hope” that catheter ablation, done in the right patients, might confer a stroke risk reduction and mortality benefit, he said.
The 33% relative risk reduction in the small group of real-world patients who failed to meet the CABANA inclusion criteria, while numerically impressive, wasn’t close to statistical significance, probably because event rates in that population were so low.
“Even if you could reduce stroke risk with ablation in that low-risk group, it would be a very inefficient way to reduce the population burden of stroke,” Dr. Noseworthy observed.
Putting together the results of CABANA and the large observational study to sum up his view of where catheter ablation for AF[ib] stands today, Dr. Noseworthy commented, “Ablation is reasonable for symptom control in many patients, basically anyone who is either breaking through on drugs or doesn’t want to take the drugs and is highly symptomatic. And there may be a small stroke and/or mortality benefit for people who are in the sweet spot – and those are people who look a lot like the patients enrolled in CABANA.”
Patients who met the exclusion criteria for CABANA are too advanced in their AFib to be likely to derive a stroke or mortality benefit from catheter ablation. “It’s very hard to move the needle in these patients with either a drug or catheter ablation approach. I wouldn’t try to reduce the risk of stroke here with an expensive and invasive procedure,” the electrophysiologist concluded.
He reported having no financial conflicts regarding his presentation.
REPORTING FROM ACC SNOWMASS 2020
Glaring gap in CV event reporting in pivotal cancer trials
Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.
Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).
Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).
“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.
The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.
“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
Lower Rate of Reported Events
The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.
Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.
To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.
Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).
There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
No malicious intent
“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”
“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”
Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.
“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”
Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.
The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.
“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.
“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
One size does not fit all
Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.
“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”
His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.
The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.
Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.
“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”
Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.
In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.
“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”
In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.
“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.
The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.
This article first appeared on Medscape.com.
Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.
Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).
Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).
“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.
The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.
“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
Lower Rate of Reported Events
The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.
Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.
To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.
Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).
There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
No malicious intent
“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”
“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”
Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.
“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”
Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.
The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.
“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.
“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
One size does not fit all
Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.
“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”
His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.
The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.
Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.
“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”
Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.
In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.
“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”
In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.
“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.
The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.
This article first appeared on Medscape.com.
Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.
Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).
Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).
“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.
The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.
“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
Lower Rate of Reported Events
The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.
Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.
To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.
Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).
There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
No malicious intent
“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”
“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”
Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.
“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”
Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.
The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.
“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.
“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
One size does not fit all
Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.
“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”
His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.
The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.
Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.
“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”
Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.
In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.
“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”
In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.
“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.
The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.
This article first appeared on Medscape.com.
Myth busting: Sudden cardiac death in athletes
SNOWMASS, COLO. – Myths and misconceptions abound regarding the merits of universal incorporation of the resting 12-lead ECG into preparticipation cardiovascular screening of young athletes, Aaron L. Baggish, MD, declared at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Dr. Baggish, director of the Cardiovascular Performance Program at Massachusetts General Hospital and a cardiologist at Harvard Medical School, Boston, set out to pop the balloons of a handful of these widely floating myths. These are commonly held fictions: In an electronic poll at the outset of his talk, only one in five members of his large audience recognized all of the following boldface statements as false.
“Preparticipation cardiovascular screening (PPCVS) has been shown to reduce the incidence of sudden cardiac death (SCD) among young competitive athletes.”
FALSE. Not for PPCVS by history and physical examination alone, or with the addition of a screening 12-lead ECG. In Italy, where a cluster of high-profile sudden cardiac deaths led to passage of a 1982 national law mandating 12-lead ECG screening as part of the PPCVS, investigators presented studies purporting to demonstrate a subsequent reduction in the risk of SCD. But those studies were subsequently shown to be fraught with problems. And a high-quality study capable of convincingly demonstrating such a benefit would need to be prohibitively large and expensive. “Don’t hold your breath waiting for that to happen anytime soon,” advised Dr. Baggish, who is medical director for the Boston Marathon, as well as team cardiologist for Harvard University Athletics, the New England Patriots, the Boston Bruins, USRowing, and U.S. Soccer.
“Hypertrophic cardiomyopathy is the leading cause of sudden death among young competitive athletes.”
FALSE. A study of the National Collegiate Athletic Association (NCAA) comprehensive database, with 4.2 million athlete-years of follow-up, showed that the most common cause of SCD was autopsy-negative sudden unexplained death (SUD), accounting for 25% of cases. Hypertrophic cardiomyopathy was deemed the cause of 8% of the SCDs (Circulation. 2015 Jul 7;132[1]:10-9).
“The same thing has been shown in studies done in the United Kingdom and in Australia: . Over the next 10 years, I suspect that one of the most important areas that we’ll be looking into will be this SUD area, perhaps using molecular autopsy to make some headway there,” according to the cardiologist.
SCD is rare. In the NCAA study, the incidence was 1 in 53,703 athlete-years. In sobering contrast, accidents, suicide, and homicide accounted for 50% of all deaths in the collegiate athletes.
“When you think about what’s important in terms of educating young people to be safe, the history and physical exam and 12-lead ECG are nowhere near as important as talking with them about minimizing accident risk and staying away from guns,” Dr. Baggish commented.
“Contemporary ECG interpretation criteria designed specifically for use in young athletes have eliminated the problem of false-positive testing.”
FALSE. The story of adding ECG screening to the PPCVS is one of dramatically improved sensitivity over history and physical exam alone, but always at the cost of reduced specificity. In the Harvard Athlete Initiative Study, Dr. Baggish and coworkers reported that adding the 12-lead ECG resulted in a 17% false-positive rate (Ann Intern Med. 2010 Mar 2;152[5]:269-75). Similar findings were reported in independent studies at two other large universities.
“An ECG false-positive rate of 16%-20%? That’s big trouble. Remember, the conditions we’re looking for are uncommon, with a prevalence of maybe 1 in 500 at most. So if you’re flagging one-fifth or one-sixth of your athletes, the ECG is really not an appropriate tool for screening,” he commented.
Recognition of this limitation has led to development of refined, improved ECG criteria: most notably, the 2012 Seattle criteria, with an associated false-positive rate of 4%-8%, followed by the 2017 International Consensus Criteria (J Am Coll Cardiol. 2017 Feb 28;69[8]:1057-75), with a false-positive rate of 1%-2%. That’s a great improvement. Still, when Dr. Baggish, a marathoner himself, thinks about the roughly 32,000 Boston Marathon runners at the starting line each year, that false-positive rate would translate into 320-640 of those individuals being needlessly subjected to the not-insignificant time and expense of further testing, along with considerable anxiety for the runners and their families, and perhaps even inappropriate disqualification.
“Current ACC/AHA guidelines recommend against the use of the 12-lead ECG during the PPCVS.”
FALSE. Dr. Baggish was a coauthor of the current guidelines, which he described as “an open-door invitation to local decisions, with some important caveats” (Circulation. 2015 Dec 1;132[22]:e267-72).
The guidelines state that the minimum requirement and legal standard for PPCVS of young competitive athletes is a focused history and physical examination, such as the American College of Cardiology/American Heart Association 14-point screen, which consists of 10 elements addressing personal and family history and 4 focused on the physical examination, or the American Academy of Pediatrics Preparticipation Physical Evaluation. Further, while mandatory universal inclusion of the 12-lead ECG is not recommended – it’s rated Class III, meaning don’t do it – the guidelines state that screening programs are at liberty to choose the 12-lead ECG as an additional tool, “provided that close physician involvement and sufficient quality control can be achieved. If undertaken, such initiatives should recognize the known and anticipated limitations of the 12-lead ECG as a population screening test, including the expected frequency of false-positive and false-negative test results, as well as the cost required to support these initiatives over time.”
Dr. Baggish considers the ACC/AHA guidelines to be one of the two most important developments in the field of SCD during sports in recent years. The other is the NCAA-sponsored multidisciplinary Interassociation Consensus Statement on Cardiovascular Care of College Student-Athletes, which he also coauthored (J Am Coll Cardiol. 2016 Jun 28;67[25]:2981-95).
The report lays out the case for a much broader than traditional view of the PPCVS, with “goals that extend beyond detection of occult high-risk pathology.”
“The NCAA has done something very interesting,” Dr. Baggish explained. “It has said that, if we’re going to be screening, we should be thinking about screening with a much broader rationale. It’s not just about finding the needle-in-a-haystack hypertrophic cardiomyopathy or anomalous coronary arteries, it’s about engaging student-athletes at an early point in their collegiate career and trying to improve their health overall – and not just while they’re in college, but over their lifespan.”
He reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – Myths and misconceptions abound regarding the merits of universal incorporation of the resting 12-lead ECG into preparticipation cardiovascular screening of young athletes, Aaron L. Baggish, MD, declared at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Dr. Baggish, director of the Cardiovascular Performance Program at Massachusetts General Hospital and a cardiologist at Harvard Medical School, Boston, set out to pop the balloons of a handful of these widely floating myths. These are commonly held fictions: In an electronic poll at the outset of his talk, only one in five members of his large audience recognized all of the following boldface statements as false.
“Preparticipation cardiovascular screening (PPCVS) has been shown to reduce the incidence of sudden cardiac death (SCD) among young competitive athletes.”
FALSE. Not for PPCVS by history and physical examination alone, or with the addition of a screening 12-lead ECG. In Italy, where a cluster of high-profile sudden cardiac deaths led to passage of a 1982 national law mandating 12-lead ECG screening as part of the PPCVS, investigators presented studies purporting to demonstrate a subsequent reduction in the risk of SCD. But those studies were subsequently shown to be fraught with problems. And a high-quality study capable of convincingly demonstrating such a benefit would need to be prohibitively large and expensive. “Don’t hold your breath waiting for that to happen anytime soon,” advised Dr. Baggish, who is medical director for the Boston Marathon, as well as team cardiologist for Harvard University Athletics, the New England Patriots, the Boston Bruins, USRowing, and U.S. Soccer.
“Hypertrophic cardiomyopathy is the leading cause of sudden death among young competitive athletes.”
FALSE. A study of the National Collegiate Athletic Association (NCAA) comprehensive database, with 4.2 million athlete-years of follow-up, showed that the most common cause of SCD was autopsy-negative sudden unexplained death (SUD), accounting for 25% of cases. Hypertrophic cardiomyopathy was deemed the cause of 8% of the SCDs (Circulation. 2015 Jul 7;132[1]:10-9).
“The same thing has been shown in studies done in the United Kingdom and in Australia: . Over the next 10 years, I suspect that one of the most important areas that we’ll be looking into will be this SUD area, perhaps using molecular autopsy to make some headway there,” according to the cardiologist.
SCD is rare. In the NCAA study, the incidence was 1 in 53,703 athlete-years. In sobering contrast, accidents, suicide, and homicide accounted for 50% of all deaths in the collegiate athletes.
“When you think about what’s important in terms of educating young people to be safe, the history and physical exam and 12-lead ECG are nowhere near as important as talking with them about minimizing accident risk and staying away from guns,” Dr. Baggish commented.
“Contemporary ECG interpretation criteria designed specifically for use in young athletes have eliminated the problem of false-positive testing.”
FALSE. The story of adding ECG screening to the PPCVS is one of dramatically improved sensitivity over history and physical exam alone, but always at the cost of reduced specificity. In the Harvard Athlete Initiative Study, Dr. Baggish and coworkers reported that adding the 12-lead ECG resulted in a 17% false-positive rate (Ann Intern Med. 2010 Mar 2;152[5]:269-75). Similar findings were reported in independent studies at two other large universities.
“An ECG false-positive rate of 16%-20%? That’s big trouble. Remember, the conditions we’re looking for are uncommon, with a prevalence of maybe 1 in 500 at most. So if you’re flagging one-fifth or one-sixth of your athletes, the ECG is really not an appropriate tool for screening,” he commented.
Recognition of this limitation has led to development of refined, improved ECG criteria: most notably, the 2012 Seattle criteria, with an associated false-positive rate of 4%-8%, followed by the 2017 International Consensus Criteria (J Am Coll Cardiol. 2017 Feb 28;69[8]:1057-75), with a false-positive rate of 1%-2%. That’s a great improvement. Still, when Dr. Baggish, a marathoner himself, thinks about the roughly 32,000 Boston Marathon runners at the starting line each year, that false-positive rate would translate into 320-640 of those individuals being needlessly subjected to the not-insignificant time and expense of further testing, along with considerable anxiety for the runners and their families, and perhaps even inappropriate disqualification.
“Current ACC/AHA guidelines recommend against the use of the 12-lead ECG during the PPCVS.”
FALSE. Dr. Baggish was a coauthor of the current guidelines, which he described as “an open-door invitation to local decisions, with some important caveats” (Circulation. 2015 Dec 1;132[22]:e267-72).
The guidelines state that the minimum requirement and legal standard for PPCVS of young competitive athletes is a focused history and physical examination, such as the American College of Cardiology/American Heart Association 14-point screen, which consists of 10 elements addressing personal and family history and 4 focused on the physical examination, or the American Academy of Pediatrics Preparticipation Physical Evaluation. Further, while mandatory universal inclusion of the 12-lead ECG is not recommended – it’s rated Class III, meaning don’t do it – the guidelines state that screening programs are at liberty to choose the 12-lead ECG as an additional tool, “provided that close physician involvement and sufficient quality control can be achieved. If undertaken, such initiatives should recognize the known and anticipated limitations of the 12-lead ECG as a population screening test, including the expected frequency of false-positive and false-negative test results, as well as the cost required to support these initiatives over time.”
Dr. Baggish considers the ACC/AHA guidelines to be one of the two most important developments in the field of SCD during sports in recent years. The other is the NCAA-sponsored multidisciplinary Interassociation Consensus Statement on Cardiovascular Care of College Student-Athletes, which he also coauthored (J Am Coll Cardiol. 2016 Jun 28;67[25]:2981-95).
The report lays out the case for a much broader than traditional view of the PPCVS, with “goals that extend beyond detection of occult high-risk pathology.”
“The NCAA has done something very interesting,” Dr. Baggish explained. “It has said that, if we’re going to be screening, we should be thinking about screening with a much broader rationale. It’s not just about finding the needle-in-a-haystack hypertrophic cardiomyopathy or anomalous coronary arteries, it’s about engaging student-athletes at an early point in their collegiate career and trying to improve their health overall – and not just while they’re in college, but over their lifespan.”
He reported having no financial conflicts regarding his presentation.
SNOWMASS, COLO. – Myths and misconceptions abound regarding the merits of universal incorporation of the resting 12-lead ECG into preparticipation cardiovascular screening of young athletes, Aaron L. Baggish, MD, declared at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
Dr. Baggish, director of the Cardiovascular Performance Program at Massachusetts General Hospital and a cardiologist at Harvard Medical School, Boston, set out to pop the balloons of a handful of these widely floating myths. These are commonly held fictions: In an electronic poll at the outset of his talk, only one in five members of his large audience recognized all of the following boldface statements as false.
“Preparticipation cardiovascular screening (PPCVS) has been shown to reduce the incidence of sudden cardiac death (SCD) among young competitive athletes.”
FALSE. Not for PPCVS by history and physical examination alone, or with the addition of a screening 12-lead ECG. In Italy, where a cluster of high-profile sudden cardiac deaths led to passage of a 1982 national law mandating 12-lead ECG screening as part of the PPCVS, investigators presented studies purporting to demonstrate a subsequent reduction in the risk of SCD. But those studies were subsequently shown to be fraught with problems. And a high-quality study capable of convincingly demonstrating such a benefit would need to be prohibitively large and expensive. “Don’t hold your breath waiting for that to happen anytime soon,” advised Dr. Baggish, who is medical director for the Boston Marathon, as well as team cardiologist for Harvard University Athletics, the New England Patriots, the Boston Bruins, USRowing, and U.S. Soccer.
“Hypertrophic cardiomyopathy is the leading cause of sudden death among young competitive athletes.”
FALSE. A study of the National Collegiate Athletic Association (NCAA) comprehensive database, with 4.2 million athlete-years of follow-up, showed that the most common cause of SCD was autopsy-negative sudden unexplained death (SUD), accounting for 25% of cases. Hypertrophic cardiomyopathy was deemed the cause of 8% of the SCDs (Circulation. 2015 Jul 7;132[1]:10-9).
“The same thing has been shown in studies done in the United Kingdom and in Australia: . Over the next 10 years, I suspect that one of the most important areas that we’ll be looking into will be this SUD area, perhaps using molecular autopsy to make some headway there,” according to the cardiologist.
SCD is rare. In the NCAA study, the incidence was 1 in 53,703 athlete-years. In sobering contrast, accidents, suicide, and homicide accounted for 50% of all deaths in the collegiate athletes.
“When you think about what’s important in terms of educating young people to be safe, the history and physical exam and 12-lead ECG are nowhere near as important as talking with them about minimizing accident risk and staying away from guns,” Dr. Baggish commented.
“Contemporary ECG interpretation criteria designed specifically for use in young athletes have eliminated the problem of false-positive testing.”
FALSE. The story of adding ECG screening to the PPCVS is one of dramatically improved sensitivity over history and physical exam alone, but always at the cost of reduced specificity. In the Harvard Athlete Initiative Study, Dr. Baggish and coworkers reported that adding the 12-lead ECG resulted in a 17% false-positive rate (Ann Intern Med. 2010 Mar 2;152[5]:269-75). Similar findings were reported in independent studies at two other large universities.
“An ECG false-positive rate of 16%-20%? That’s big trouble. Remember, the conditions we’re looking for are uncommon, with a prevalence of maybe 1 in 500 at most. So if you’re flagging one-fifth or one-sixth of your athletes, the ECG is really not an appropriate tool for screening,” he commented.
Recognition of this limitation has led to development of refined, improved ECG criteria: most notably, the 2012 Seattle criteria, with an associated false-positive rate of 4%-8%, followed by the 2017 International Consensus Criteria (J Am Coll Cardiol. 2017 Feb 28;69[8]:1057-75), with a false-positive rate of 1%-2%. That’s a great improvement. Still, when Dr. Baggish, a marathoner himself, thinks about the roughly 32,000 Boston Marathon runners at the starting line each year, that false-positive rate would translate into 320-640 of those individuals being needlessly subjected to the not-insignificant time and expense of further testing, along with considerable anxiety for the runners and their families, and perhaps even inappropriate disqualification.
“Current ACC/AHA guidelines recommend against the use of the 12-lead ECG during the PPCVS.”
FALSE. Dr. Baggish was a coauthor of the current guidelines, which he described as “an open-door invitation to local decisions, with some important caveats” (Circulation. 2015 Dec 1;132[22]:e267-72).
The guidelines state that the minimum requirement and legal standard for PPCVS of young competitive athletes is a focused history and physical examination, such as the American College of Cardiology/American Heart Association 14-point screen, which consists of 10 elements addressing personal and family history and 4 focused on the physical examination, or the American Academy of Pediatrics Preparticipation Physical Evaluation. Further, while mandatory universal inclusion of the 12-lead ECG is not recommended – it’s rated Class III, meaning don’t do it – the guidelines state that screening programs are at liberty to choose the 12-lead ECG as an additional tool, “provided that close physician involvement and sufficient quality control can be achieved. If undertaken, such initiatives should recognize the known and anticipated limitations of the 12-lead ECG as a population screening test, including the expected frequency of false-positive and false-negative test results, as well as the cost required to support these initiatives over time.”
Dr. Baggish considers the ACC/AHA guidelines to be one of the two most important developments in the field of SCD during sports in recent years. The other is the NCAA-sponsored multidisciplinary Interassociation Consensus Statement on Cardiovascular Care of College Student-Athletes, which he also coauthored (J Am Coll Cardiol. 2016 Jun 28;67[25]:2981-95).
The report lays out the case for a much broader than traditional view of the PPCVS, with “goals that extend beyond detection of occult high-risk pathology.”
“The NCAA has done something very interesting,” Dr. Baggish explained. “It has said that, if we’re going to be screening, we should be thinking about screening with a much broader rationale. It’s not just about finding the needle-in-a-haystack hypertrophic cardiomyopathy or anomalous coronary arteries, it’s about engaging student-athletes at an early point in their collegiate career and trying to improve their health overall – and not just while they’re in college, but over their lifespan.”
He reported having no financial conflicts regarding his presentation.
REPORTING FROM ACC SNOWMASS 2020
FDA issues public health warning recommending against cesium salt usage
The Food and Drug Administration has issued a public health alert warning consumers to avoid the use of dietary supplements that contain cesium chloride or any other cesium salt because of significant safety risks.
Cesium salts are sometimes advertised as an alternative treatment for cancer, the FDA said in the announcement, but these salts have never proved to be safe or effective at treating cancer or any other disease. Clinical case reports and nonclinical trials have shown that cesium salts are associated with a variety of adverse events, including cardiac arrhythmias, hypokalemia, seizures, syncope, and death.
The FDA warned health care providers that cesium salts presented a significant safety risk in compounding drugs in July 2018.
Health care providers should not recommend dietary supplements containing cesium salts to their patients, the FDA said, and if a patient experiences an adverse event while taking a supplement containing cesium salt, the event should be reported to the agency.
While there are few dietary supplements on the market that contain cesium salt, consumers should be aware of the risks and avoid these products. The FDA noted that “if claims sound too good to be true, they probably are.”
The Food and Drug Administration has issued a public health alert warning consumers to avoid the use of dietary supplements that contain cesium chloride or any other cesium salt because of significant safety risks.
Cesium salts are sometimes advertised as an alternative treatment for cancer, the FDA said in the announcement, but these salts have never proved to be safe or effective at treating cancer or any other disease. Clinical case reports and nonclinical trials have shown that cesium salts are associated with a variety of adverse events, including cardiac arrhythmias, hypokalemia, seizures, syncope, and death.
The FDA warned health care providers that cesium salts presented a significant safety risk in compounding drugs in July 2018.
Health care providers should not recommend dietary supplements containing cesium salts to their patients, the FDA said, and if a patient experiences an adverse event while taking a supplement containing cesium salt, the event should be reported to the agency.
While there are few dietary supplements on the market that contain cesium salt, consumers should be aware of the risks and avoid these products. The FDA noted that “if claims sound too good to be true, they probably are.”
The Food and Drug Administration has issued a public health alert warning consumers to avoid the use of dietary supplements that contain cesium chloride or any other cesium salt because of significant safety risks.
Cesium salts are sometimes advertised as an alternative treatment for cancer, the FDA said in the announcement, but these salts have never proved to be safe or effective at treating cancer or any other disease. Clinical case reports and nonclinical trials have shown that cesium salts are associated with a variety of adverse events, including cardiac arrhythmias, hypokalemia, seizures, syncope, and death.
The FDA warned health care providers that cesium salts presented a significant safety risk in compounding drugs in July 2018.
Health care providers should not recommend dietary supplements containing cesium salts to their patients, the FDA said, and if a patient experiences an adverse event while taking a supplement containing cesium salt, the event should be reported to the agency.
While there are few dietary supplements on the market that contain cesium salt, consumers should be aware of the risks and avoid these products. The FDA noted that “if claims sound too good to be true, they probably are.”
Heart rhythm data from wearables confounds EP practice
NATIONAL HARBOR, MD. – or other warnings that flagged a possible cardiac arrhythmia.
While the clinical community has yet to reach an evidence-based consensus on how to deal with this information, or even asymptomatic arrhythmias identified by more standard means, the American public is voting with their wrists. People seem to like collecting and reviewing readouts on their heart rhythm and other vital data, and then they often take their numbers to a physician, especially when their device suggests a possible problem.
“The whole paradigm of ordering a test only if you intend to act on the result has been flipped. People now get what they want directly, and our job is to guide them” after the fact. “You need to teach people what’s actionable and what’s not,” Mintu P. Turakhia, MD, said at the annual International AF Symposium.
“We’re in a situation where the ability of a sensor to detect things is separate from access to the health care system. They are no longer coupled; they are disjointed. People can create their own ICU in their house just by shopping online, but what do we do with this information, whether it’s an irregular heart rhythm or their whole genome?” asked Dr. Turakhia, executive director of the Center for Digital Health at Stanford (Calif.) University and director of cardiac electrophysiology at the VA Palo Alto (Calif.) Health Care System.
“The main challenge is people without a diagnosis who get a notification. How much monitoring should you do until you can say it was a false positive? We don’t know what to do, so we monitor them. People are trying to figure this out.” Dr. Turakhia said. Some people who seek out electrophysiologists this way “may not even have a primary care physician,” he noted.
The potential implications of widespread monitoring for heartbeat irregularities in the general public began to surface in a study that Dr. Turakhia helped run that collected wearable data from nearly 420,000 Americans. Results from the Apple Heart Study showed that, during a median 117 days of monitoring with a smart watch, 2,161 people (0.5%) received a report of an irregular pulse, which led to further investigations that eventually diagnosed atrial fibrillation (AFib) in 153 people of the 450 who underwent follow-up assessment (N Engl J Med. 2019 Nov 14;381[20]:1909-17). These results “raise questions” about the large number of people who underwent follow-up testing who did not have arrhythmia, Dr. Turakhia noted.
“The dissemination of wearables has been quite dramatic, and electrophysiologists end up owning this,” commented Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director emeritus of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “I get a ton of calls from people whom I wish never bought a smart watch, and they say ‘I have atrial fibrillation. What do I do?’ ”
To document the growth of this trend, Dr. Turakhia cited results from a survey he collaborated on, run by Stanford and Rock Health, that found a 33% ownership rate among American adults of a wearable device capable of collecting health data, and a 42% rate of people who tracked their health data with a device, app, journal, or log. Both of these rates more than doubled what a similar survey found in 2015.
The cardiac electrophysiology community took a first step toward addressing one aspect of this evolving situation. In early 2020, the Heart Rhythm Society and the Consumer Technology Association jointly issued a guidance document targeted at consumers that walks them through the kinds of information their wearable devices might collect and how to approach this information. The main message: If you have questions or concerns about your data, consult a clinician. What remains in short supply is guidance to clinicians on what to do when they see these patients.
“Until recently, device-detected AFib was the sole purview of electrophysiologists using implanted rhythm-monitoring devices. Now mobile and other devices raise issues [of asymptomatic AFib] for a much broader population,” noted Daniel E. Singer, MD, professor of medicine and epidemiology at Harvard and Massachusetts General Hospital. “The world of device-detected AFib now includes watches.”
Researchers have tried for years to better understand the stroke risk faced by patients with asymptomatic or subclinical AFib that’s detected by an implanted device, as in the ASSERT study of nearly 2,600 patients followed for a median of 2.5 years that found an increased stroke risk when the duration of individual, subclinical AFib episodes surpassed 24 hours (Eur Heart J. 2017 May 1;38[17]:1339-44). More recently, a study of AFib duration collected by implanted cardiac devices in nearly 22,000 Americans showed a relationship between stroke risk and both the duration of AFib episodes and the underlying risk of a person for stroke as measured by their CHA2DS2-VAScscore (Circulation. 2019 Nov 12;140[20]:1639-46). Just under 30% of patients in the study were diagnosed with AFib at entry.
The implications of asymptomatic episodes of AFib have so far been largely studied in people with an implanted cardiac device, which may have limited applicability to wearable users. In addition, the field has not yet fully sorted out the relationships between the duration of individual AFib episodes and overall AFib burden, and a person’s stroke risk and the window of time when the potential stroke-preventing benefits of anticoagulation outweigh its bleeding risk.
The results of trials now in progress that are examining the safety and efficacy of medical interventions designed to avert strokes in patients with asymptomatic AFib “will bear on the use of anticoagulants in a large group of patients,” including people with AFib detected by a wearable, Dr. Singer predicted.
The Apple Heart Study was sponsored Apple. Dr. Turakhia has received funding from Apple, and he has received honoraria or research funding from several other companies. Dr. Ruskin has been a consultant or adviser to several companies, is a steering committee member for Pfizer, and holds equity or options in Portola, Element Science, NewPace, Gilead, and InfoBionic. Dr. Singer has been a consultant and adviser to Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Merck, and Pfizer, and he has received research grants from Bristol-Myers Squibb.
NATIONAL HARBOR, MD. – or other warnings that flagged a possible cardiac arrhythmia.
While the clinical community has yet to reach an evidence-based consensus on how to deal with this information, or even asymptomatic arrhythmias identified by more standard means, the American public is voting with their wrists. People seem to like collecting and reviewing readouts on their heart rhythm and other vital data, and then they often take their numbers to a physician, especially when their device suggests a possible problem.
“The whole paradigm of ordering a test only if you intend to act on the result has been flipped. People now get what they want directly, and our job is to guide them” after the fact. “You need to teach people what’s actionable and what’s not,” Mintu P. Turakhia, MD, said at the annual International AF Symposium.
“We’re in a situation where the ability of a sensor to detect things is separate from access to the health care system. They are no longer coupled; they are disjointed. People can create their own ICU in their house just by shopping online, but what do we do with this information, whether it’s an irregular heart rhythm or their whole genome?” asked Dr. Turakhia, executive director of the Center for Digital Health at Stanford (Calif.) University and director of cardiac electrophysiology at the VA Palo Alto (Calif.) Health Care System.
“The main challenge is people without a diagnosis who get a notification. How much monitoring should you do until you can say it was a false positive? We don’t know what to do, so we monitor them. People are trying to figure this out.” Dr. Turakhia said. Some people who seek out electrophysiologists this way “may not even have a primary care physician,” he noted.
The potential implications of widespread monitoring for heartbeat irregularities in the general public began to surface in a study that Dr. Turakhia helped run that collected wearable data from nearly 420,000 Americans. Results from the Apple Heart Study showed that, during a median 117 days of monitoring with a smart watch, 2,161 people (0.5%) received a report of an irregular pulse, which led to further investigations that eventually diagnosed atrial fibrillation (AFib) in 153 people of the 450 who underwent follow-up assessment (N Engl J Med. 2019 Nov 14;381[20]:1909-17). These results “raise questions” about the large number of people who underwent follow-up testing who did not have arrhythmia, Dr. Turakhia noted.
“The dissemination of wearables has been quite dramatic, and electrophysiologists end up owning this,” commented Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director emeritus of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “I get a ton of calls from people whom I wish never bought a smart watch, and they say ‘I have atrial fibrillation. What do I do?’ ”
To document the growth of this trend, Dr. Turakhia cited results from a survey he collaborated on, run by Stanford and Rock Health, that found a 33% ownership rate among American adults of a wearable device capable of collecting health data, and a 42% rate of people who tracked their health data with a device, app, journal, or log. Both of these rates more than doubled what a similar survey found in 2015.
The cardiac electrophysiology community took a first step toward addressing one aspect of this evolving situation. In early 2020, the Heart Rhythm Society and the Consumer Technology Association jointly issued a guidance document targeted at consumers that walks them through the kinds of information their wearable devices might collect and how to approach this information. The main message: If you have questions or concerns about your data, consult a clinician. What remains in short supply is guidance to clinicians on what to do when they see these patients.
“Until recently, device-detected AFib was the sole purview of electrophysiologists using implanted rhythm-monitoring devices. Now mobile and other devices raise issues [of asymptomatic AFib] for a much broader population,” noted Daniel E. Singer, MD, professor of medicine and epidemiology at Harvard and Massachusetts General Hospital. “The world of device-detected AFib now includes watches.”
Researchers have tried for years to better understand the stroke risk faced by patients with asymptomatic or subclinical AFib that’s detected by an implanted device, as in the ASSERT study of nearly 2,600 patients followed for a median of 2.5 years that found an increased stroke risk when the duration of individual, subclinical AFib episodes surpassed 24 hours (Eur Heart J. 2017 May 1;38[17]:1339-44). More recently, a study of AFib duration collected by implanted cardiac devices in nearly 22,000 Americans showed a relationship between stroke risk and both the duration of AFib episodes and the underlying risk of a person for stroke as measured by their CHA2DS2-VAScscore (Circulation. 2019 Nov 12;140[20]:1639-46). Just under 30% of patients in the study were diagnosed with AFib at entry.
The implications of asymptomatic episodes of AFib have so far been largely studied in people with an implanted cardiac device, which may have limited applicability to wearable users. In addition, the field has not yet fully sorted out the relationships between the duration of individual AFib episodes and overall AFib burden, and a person’s stroke risk and the window of time when the potential stroke-preventing benefits of anticoagulation outweigh its bleeding risk.
The results of trials now in progress that are examining the safety and efficacy of medical interventions designed to avert strokes in patients with asymptomatic AFib “will bear on the use of anticoagulants in a large group of patients,” including people with AFib detected by a wearable, Dr. Singer predicted.
The Apple Heart Study was sponsored Apple. Dr. Turakhia has received funding from Apple, and he has received honoraria or research funding from several other companies. Dr. Ruskin has been a consultant or adviser to several companies, is a steering committee member for Pfizer, and holds equity or options in Portola, Element Science, NewPace, Gilead, and InfoBionic. Dr. Singer has been a consultant and adviser to Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Merck, and Pfizer, and he has received research grants from Bristol-Myers Squibb.
NATIONAL HARBOR, MD. – or other warnings that flagged a possible cardiac arrhythmia.
While the clinical community has yet to reach an evidence-based consensus on how to deal with this information, or even asymptomatic arrhythmias identified by more standard means, the American public is voting with their wrists. People seem to like collecting and reviewing readouts on their heart rhythm and other vital data, and then they often take their numbers to a physician, especially when their device suggests a possible problem.
“The whole paradigm of ordering a test only if you intend to act on the result has been flipped. People now get what they want directly, and our job is to guide them” after the fact. “You need to teach people what’s actionable and what’s not,” Mintu P. Turakhia, MD, said at the annual International AF Symposium.
“We’re in a situation where the ability of a sensor to detect things is separate from access to the health care system. They are no longer coupled; they are disjointed. People can create their own ICU in their house just by shopping online, but what do we do with this information, whether it’s an irregular heart rhythm or their whole genome?” asked Dr. Turakhia, executive director of the Center for Digital Health at Stanford (Calif.) University and director of cardiac electrophysiology at the VA Palo Alto (Calif.) Health Care System.
“The main challenge is people without a diagnosis who get a notification. How much monitoring should you do until you can say it was a false positive? We don’t know what to do, so we monitor them. People are trying to figure this out.” Dr. Turakhia said. Some people who seek out electrophysiologists this way “may not even have a primary care physician,” he noted.
The potential implications of widespread monitoring for heartbeat irregularities in the general public began to surface in a study that Dr. Turakhia helped run that collected wearable data from nearly 420,000 Americans. Results from the Apple Heart Study showed that, during a median 117 days of monitoring with a smart watch, 2,161 people (0.5%) received a report of an irregular pulse, which led to further investigations that eventually diagnosed atrial fibrillation (AFib) in 153 people of the 450 who underwent follow-up assessment (N Engl J Med. 2019 Nov 14;381[20]:1909-17). These results “raise questions” about the large number of people who underwent follow-up testing who did not have arrhythmia, Dr. Turakhia noted.
“The dissemination of wearables has been quite dramatic, and electrophysiologists end up owning this,” commented Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director emeritus of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “I get a ton of calls from people whom I wish never bought a smart watch, and they say ‘I have atrial fibrillation. What do I do?’ ”
To document the growth of this trend, Dr. Turakhia cited results from a survey he collaborated on, run by Stanford and Rock Health, that found a 33% ownership rate among American adults of a wearable device capable of collecting health data, and a 42% rate of people who tracked their health data with a device, app, journal, or log. Both of these rates more than doubled what a similar survey found in 2015.
The cardiac electrophysiology community took a first step toward addressing one aspect of this evolving situation. In early 2020, the Heart Rhythm Society and the Consumer Technology Association jointly issued a guidance document targeted at consumers that walks them through the kinds of information their wearable devices might collect and how to approach this information. The main message: If you have questions or concerns about your data, consult a clinician. What remains in short supply is guidance to clinicians on what to do when they see these patients.
“Until recently, device-detected AFib was the sole purview of electrophysiologists using implanted rhythm-monitoring devices. Now mobile and other devices raise issues [of asymptomatic AFib] for a much broader population,” noted Daniel E. Singer, MD, professor of medicine and epidemiology at Harvard and Massachusetts General Hospital. “The world of device-detected AFib now includes watches.”
Researchers have tried for years to better understand the stroke risk faced by patients with asymptomatic or subclinical AFib that’s detected by an implanted device, as in the ASSERT study of nearly 2,600 patients followed for a median of 2.5 years that found an increased stroke risk when the duration of individual, subclinical AFib episodes surpassed 24 hours (Eur Heart J. 2017 May 1;38[17]:1339-44). More recently, a study of AFib duration collected by implanted cardiac devices in nearly 22,000 Americans showed a relationship between stroke risk and both the duration of AFib episodes and the underlying risk of a person for stroke as measured by their CHA2DS2-VAScscore (Circulation. 2019 Nov 12;140[20]:1639-46). Just under 30% of patients in the study were diagnosed with AFib at entry.
The implications of asymptomatic episodes of AFib have so far been largely studied in people with an implanted cardiac device, which may have limited applicability to wearable users. In addition, the field has not yet fully sorted out the relationships between the duration of individual AFib episodes and overall AFib burden, and a person’s stroke risk and the window of time when the potential stroke-preventing benefits of anticoagulation outweigh its bleeding risk.
The results of trials now in progress that are examining the safety and efficacy of medical interventions designed to avert strokes in patients with asymptomatic AFib “will bear on the use of anticoagulants in a large group of patients,” including people with AFib detected by a wearable, Dr. Singer predicted.
The Apple Heart Study was sponsored Apple. Dr. Turakhia has received funding from Apple, and he has received honoraria or research funding from several other companies. Dr. Ruskin has been a consultant or adviser to several companies, is a steering committee member for Pfizer, and holds equity or options in Portola, Element Science, NewPace, Gilead, and InfoBionic. Dr. Singer has been a consultant and adviser to Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Merck, and Pfizer, and he has received research grants from Bristol-Myers Squibb.
REPORTING FROM THE AF SYMPOSIUM 2020
Expanded indication for leadless pacemaker triples eligible patients
The U.S. Food and Drug Administration’s approval of an expanded indication for a leadless pacemaker for patients “who may benefit from maintenance of atrioventricular synchrony” will make this technology potentially available to nearly half of the Americans who need a pacemaker, roughly triple the number of patients who have been candidates for a leadless pacemaker up to now.
“This approval was huge. The complication rate with leadless pacemakers has been 63% less than the rate using pacemakers with transvenous leads,” said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication. By expanding the types of patients suitable for leadless pacing “we’ll achieve AV [atrioventricular] synchrony in more patients with fewer complications,” said Dr. Chinitz, professor of medicine and director of the Cardiac Electrophysiology and Heart Rhythm Center at NYU Langone Health in New York.
Because the device is both leadless and requires no pocket owing to its small size and placement in a patient’s right ventricle, it has implications for potentially broadening the population that could benefit from the device, he said in an interview. “When we started with this pacemaker, it was limited to elderly patients with persistent atrial fibrillation who needed only ventricular pacing, a very small group,” just under 15% of the universe of patients who need pacemakers. The broadened indication, for patients with high-grade AV block who also have atrial function, makes it possible to think of using this safer and easier-to-place device in patients who need infrequent pacing, and in patients with multiple comorbidities that give them an increased complication risk, he said. The new indication means “you’re treating a much broader patient population, doing it more safely, and creating the foundation for expanding this technology.”
The Micra AV pacemaker uses the same basic design as the previously approved Micra Transcatheter Pacing System, which came onto the U.S. market in 2016 and provides single-chamber pacing. An accelerometer on the device allows it to detect atrial motion and thereby synchronize ventricular and atrial contractions, which led to the new indication. Although the Micra AV device looks similar to the original single-chamber model, it has an entirely new circuitry that prolongs battery life during dual-chamber pacing as well as new software that incorporates the accelerometer data, explained Robert Kowal, MD, a cardiac electrophysiologist, and vice president of medical affairs and chief medical officer of cardiac rhythm and heart failure at Medtronic in Minneapolis. The battery of the Micra AV is designed to last about 15 years, Dr. Chinitz noted.
Results from two studies that Dr. Chinitz helped run established the safety and efficacy of the device for dual-chamber pacing. The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study included 64 patients who completed the study at 12 worldwide centers, which produced an average 80% AV synchrony in 33 patients with high-degree AV block (The other patients in the study had predominantly intrinsic AV conduction; Heart Rhythm. 2018 Sep;15[9]:1363-71). The MARVEL 2 study included 75 patients with either second- or third-degree AV block at 12 worldwide centers and showed that AV synchrony increased from an average of 27% without two-chamber pacing to 89% with the dual-chamber function turned on, and with 95% of patients achieving at least 70% AV synchrony (JACC Clin Electrophysiol. 2020 Jan;6[1]:94-106).
The 2016 indication for single-chamber pacing included patients with “high-grade” AV bloc with or without atrial fibrillation, typically patients for whom dual-chamber pacemaker was not a great option because of the risks for complication but with the downside of limited AV synchrony, a limitation now mitigated by the option of mechanical synchronization, Dr. Kowal said. The AV device remains intended for patients with high-grade AV node block, which means patients with second- or third-degree block, he added in an interview. The estimated prevalence of third-degree AV block among U.S. adults is about 0.02%, which translates into about 50,000 people; the estimated prevalence of second-degree AV block is much less, about 10% of the third-degree prevalence.
Despite the substantial cut in complications by a leadless and pocketless pacemaker, “some patients may still benefit from a traditional dual-chamber pacemaker,” specifically active patients who might sometimes get their heart rates up with exercise to levels of about 150 beats/min or higher, Dr. Kowal said. That’s because currently the programing algorithms used to synchronize the ventricle and atrium become less reliable at heart rates above 105 beats/min, he explained. However, the ability for mechanical synchronization to keep up at higher heart rates should improve as additional data are collected that can refine the algorithms. It’s also unusual for most patients who are pacemaker candidates to reach heart rates this high, he said.
The MARVEL and MARVEL 2 studies were sponsored by Medtronic, the company that markets Micra pacemakers. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer, and he has also received fellowship support from Biotronik and Boston Scientific. Dr. Kowal is a Medtronic employee.
The U.S. Food and Drug Administration’s approval of an expanded indication for a leadless pacemaker for patients “who may benefit from maintenance of atrioventricular synchrony” will make this technology potentially available to nearly half of the Americans who need a pacemaker, roughly triple the number of patients who have been candidates for a leadless pacemaker up to now.
“This approval was huge. The complication rate with leadless pacemakers has been 63% less than the rate using pacemakers with transvenous leads,” said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication. By expanding the types of patients suitable for leadless pacing “we’ll achieve AV [atrioventricular] synchrony in more patients with fewer complications,” said Dr. Chinitz, professor of medicine and director of the Cardiac Electrophysiology and Heart Rhythm Center at NYU Langone Health in New York.
Because the device is both leadless and requires no pocket owing to its small size and placement in a patient’s right ventricle, it has implications for potentially broadening the population that could benefit from the device, he said in an interview. “When we started with this pacemaker, it was limited to elderly patients with persistent atrial fibrillation who needed only ventricular pacing, a very small group,” just under 15% of the universe of patients who need pacemakers. The broadened indication, for patients with high-grade AV block who also have atrial function, makes it possible to think of using this safer and easier-to-place device in patients who need infrequent pacing, and in patients with multiple comorbidities that give them an increased complication risk, he said. The new indication means “you’re treating a much broader patient population, doing it more safely, and creating the foundation for expanding this technology.”
The Micra AV pacemaker uses the same basic design as the previously approved Micra Transcatheter Pacing System, which came onto the U.S. market in 2016 and provides single-chamber pacing. An accelerometer on the device allows it to detect atrial motion and thereby synchronize ventricular and atrial contractions, which led to the new indication. Although the Micra AV device looks similar to the original single-chamber model, it has an entirely new circuitry that prolongs battery life during dual-chamber pacing as well as new software that incorporates the accelerometer data, explained Robert Kowal, MD, a cardiac electrophysiologist, and vice president of medical affairs and chief medical officer of cardiac rhythm and heart failure at Medtronic in Minneapolis. The battery of the Micra AV is designed to last about 15 years, Dr. Chinitz noted.
Results from two studies that Dr. Chinitz helped run established the safety and efficacy of the device for dual-chamber pacing. The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study included 64 patients who completed the study at 12 worldwide centers, which produced an average 80% AV synchrony in 33 patients with high-degree AV block (The other patients in the study had predominantly intrinsic AV conduction; Heart Rhythm. 2018 Sep;15[9]:1363-71). The MARVEL 2 study included 75 patients with either second- or third-degree AV block at 12 worldwide centers and showed that AV synchrony increased from an average of 27% without two-chamber pacing to 89% with the dual-chamber function turned on, and with 95% of patients achieving at least 70% AV synchrony (JACC Clin Electrophysiol. 2020 Jan;6[1]:94-106).
The 2016 indication for single-chamber pacing included patients with “high-grade” AV bloc with or without atrial fibrillation, typically patients for whom dual-chamber pacemaker was not a great option because of the risks for complication but with the downside of limited AV synchrony, a limitation now mitigated by the option of mechanical synchronization, Dr. Kowal said. The AV device remains intended for patients with high-grade AV node block, which means patients with second- or third-degree block, he added in an interview. The estimated prevalence of third-degree AV block among U.S. adults is about 0.02%, which translates into about 50,000 people; the estimated prevalence of second-degree AV block is much less, about 10% of the third-degree prevalence.
Despite the substantial cut in complications by a leadless and pocketless pacemaker, “some patients may still benefit from a traditional dual-chamber pacemaker,” specifically active patients who might sometimes get their heart rates up with exercise to levels of about 150 beats/min or higher, Dr. Kowal said. That’s because currently the programing algorithms used to synchronize the ventricle and atrium become less reliable at heart rates above 105 beats/min, he explained. However, the ability for mechanical synchronization to keep up at higher heart rates should improve as additional data are collected that can refine the algorithms. It’s also unusual for most patients who are pacemaker candidates to reach heart rates this high, he said.
The MARVEL and MARVEL 2 studies were sponsored by Medtronic, the company that markets Micra pacemakers. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer, and he has also received fellowship support from Biotronik and Boston Scientific. Dr. Kowal is a Medtronic employee.
The U.S. Food and Drug Administration’s approval of an expanded indication for a leadless pacemaker for patients “who may benefit from maintenance of atrioventricular synchrony” will make this technology potentially available to nearly half of the Americans who need a pacemaker, roughly triple the number of patients who have been candidates for a leadless pacemaker up to now.
“This approval was huge. The complication rate with leadless pacemakers has been 63% less than the rate using pacemakers with transvenous leads,” said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication. By expanding the types of patients suitable for leadless pacing “we’ll achieve AV [atrioventricular] synchrony in more patients with fewer complications,” said Dr. Chinitz, professor of medicine and director of the Cardiac Electrophysiology and Heart Rhythm Center at NYU Langone Health in New York.
Because the device is both leadless and requires no pocket owing to its small size and placement in a patient’s right ventricle, it has implications for potentially broadening the population that could benefit from the device, he said in an interview. “When we started with this pacemaker, it was limited to elderly patients with persistent atrial fibrillation who needed only ventricular pacing, a very small group,” just under 15% of the universe of patients who need pacemakers. The broadened indication, for patients with high-grade AV block who also have atrial function, makes it possible to think of using this safer and easier-to-place device in patients who need infrequent pacing, and in patients with multiple comorbidities that give them an increased complication risk, he said. The new indication means “you’re treating a much broader patient population, doing it more safely, and creating the foundation for expanding this technology.”
The Micra AV pacemaker uses the same basic design as the previously approved Micra Transcatheter Pacing System, which came onto the U.S. market in 2016 and provides single-chamber pacing. An accelerometer on the device allows it to detect atrial motion and thereby synchronize ventricular and atrial contractions, which led to the new indication. Although the Micra AV device looks similar to the original single-chamber model, it has an entirely new circuitry that prolongs battery life during dual-chamber pacing as well as new software that incorporates the accelerometer data, explained Robert Kowal, MD, a cardiac electrophysiologist, and vice president of medical affairs and chief medical officer of cardiac rhythm and heart failure at Medtronic in Minneapolis. The battery of the Micra AV is designed to last about 15 years, Dr. Chinitz noted.
Results from two studies that Dr. Chinitz helped run established the safety and efficacy of the device for dual-chamber pacing. The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study included 64 patients who completed the study at 12 worldwide centers, which produced an average 80% AV synchrony in 33 patients with high-degree AV block (The other patients in the study had predominantly intrinsic AV conduction; Heart Rhythm. 2018 Sep;15[9]:1363-71). The MARVEL 2 study included 75 patients with either second- or third-degree AV block at 12 worldwide centers and showed that AV synchrony increased from an average of 27% without two-chamber pacing to 89% with the dual-chamber function turned on, and with 95% of patients achieving at least 70% AV synchrony (JACC Clin Electrophysiol. 2020 Jan;6[1]:94-106).
The 2016 indication for single-chamber pacing included patients with “high-grade” AV bloc with or without atrial fibrillation, typically patients for whom dual-chamber pacemaker was not a great option because of the risks for complication but with the downside of limited AV synchrony, a limitation now mitigated by the option of mechanical synchronization, Dr. Kowal said. The AV device remains intended for patients with high-grade AV node block, which means patients with second- or third-degree block, he added in an interview. The estimated prevalence of third-degree AV block among U.S. adults is about 0.02%, which translates into about 50,000 people; the estimated prevalence of second-degree AV block is much less, about 10% of the third-degree prevalence.
Despite the substantial cut in complications by a leadless and pocketless pacemaker, “some patients may still benefit from a traditional dual-chamber pacemaker,” specifically active patients who might sometimes get their heart rates up with exercise to levels of about 150 beats/min or higher, Dr. Kowal said. That’s because currently the programing algorithms used to synchronize the ventricle and atrium become less reliable at heart rates above 105 beats/min, he explained. However, the ability for mechanical synchronization to keep up at higher heart rates should improve as additional data are collected that can refine the algorithms. It’s also unusual for most patients who are pacemaker candidates to reach heart rates this high, he said.
The MARVEL and MARVEL 2 studies were sponsored by Medtronic, the company that markets Micra pacemakers. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer, and he has also received fellowship support from Biotronik and Boston Scientific. Dr. Kowal is a Medtronic employee.