Mitchel L. Zoler, PhD

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

[email protected]

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

[email protected]

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

[email protected]

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.

“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.

When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.

“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.

The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.

“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.

“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.

An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.

This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.

MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.

The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).

MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.

[email protected]

SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.

HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.

“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.

When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.

“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.

The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.

“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.

“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.

An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.

This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.

MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.

The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).

MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.

[email protected]

SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.

HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.

“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.

When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.

“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.

The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.

“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.

“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.

An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.

This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.

MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.

The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).

MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.

[email protected]

SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.

HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and by the third quarter of 2018, a nationwide U.S. program aimed at boosting the number of stroke patients who receive thrombolysis in a timely way met its most recent speed targets.

Mitchel L. Zoler/MDedge News

By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.

The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.

“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”

During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.

Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.

The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.

The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.

With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
 

[email protected]

SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.

HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and by the third quarter of 2018, a nationwide U.S. program aimed at boosting the number of stroke patients who receive thrombolysis in a timely way met its most recent speed targets.

Mitchel L. Zoler/MDedge News

By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.

The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.

“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”

During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.

Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.

The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.

The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.

With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
 

[email protected]

SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.

HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and by the third quarter of 2018, a nationwide U.S. program aimed at boosting the number of stroke patients who receive thrombolysis in a timely way met its most recent speed targets.

Mitchel L. Zoler/MDedge News

By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.

The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.

“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”

During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.

Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.

The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.

The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.

With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
 

[email protected]

SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.

HONOLULU – In patients who were hyperglycemic following an acute ischemic stroke, intensive insulin control using a continuous insulin drip and an aggressive blood glucose target of 80-130 mg/dL provided no incremental benefit in clinical outcome, compared with a more standard approach of serial, subcutaneous insulin injections and a moderate blood glucose target in a multicenter, U.S. trial with more than 1,100 patients.

Mitchel L. Zoler/MDedge News

The results also highlighted the potential downside to aggressive insulin treatment, with an associated 2.6% incidence of severe hypoglycemia, defined as blood glucose falling below 40 mg/dL, Karen C. Johnston, MD, said at the International Stroke Conference sponsored by the American Heart Association.

“Our data suggest that subcutaneously administered insulin with a target blood glucose level of less than 180 mg/dL is the preferred treatment” because it produces similar efficacy without causing any episodes of severe hypoglycemia, concluded Dr. Johnston, professor and chair of neurology at the University of Virginia in Charlottesville. “There should be no further debate” over the potential superiority of a glucose target substantially below 180 mg/dL, she added in an interview.

Continuing to use a glucose target of less than 180 mg/dL and treating patients with subcutaneous insulin injections every 6 hours to achieve this will mean substantially less resource use and precludes the need for keeping patients in intensive care beds as is needed with an insulin drip, Dr. Johnston noted. A treatment target of less than 180 mg/dL is also consistent with the most recent American Heart Association stroke treatment guidelines, which listed a blood glucose target of 140-180 mg/dL as a class IIa recommendation (Stroke. 2018 March;49[3]:e66-99).

The SHINE (Stroke Hyperglycemia Insulin Network Effort) trial enrolled 1,151 adults diagnosed with an acute ischemic stroke at 63 U.S. centers during 2012-2018, excluding patients with type 1 diabetes. Patients had to enter the study within 12 hours of their last known well time, and with an elevated blood glucose level, above 110 mg/dL in patients with type 2 diabetes or at or above 150 mg/dL in other patients. The median glucose level of enrolled patients was about 188 mg/dL. Enrolled patients averaged 66 years old, and about 80% had type 2 diabetes. The median time from last known well to randomization was just over 7 hours. Almost two-thirds of the patients received thrombolytic treatment, and about 13% underwent thrombectomy.

During up to 72 hours of treatment following enrollment the patients in the standard-treatment arm showed a fairly steady average blood glucose level of 179 mg/dL; patients in the intensive arm showed a steady average of 118 mg/dL.

The study’s primary end point was the percentage of patients with a favorable outcome 90 days after enrollment based on their modified Rankin scale score at that time, with the scores that qualified for this end point varying depending on stroke severity at baseline. The percentage of patients achieving this was 20.5% among the intensive patients and 21.6% among those who received standard insulin treatment, a difference that was not statistically significant.

The findings left open the question of how to better manage acute ischemic stroke patients who present with hyperglycemia.

“Hyperglycemic stroke patients have worse outcomes than stroke patients without hyperglycemia. More aggressively treating the hyperglycemia did not help these patients, We need to figure out what will help them,” Dr. Johnson said.

[email protected]

SOURCE: Johnston KC et al. ISC 2019, Abstract LB1.

HONOLULU – In patients who were hyperglycemic following an acute ischemic stroke, intensive insulin control using a continuous insulin drip and an aggressive blood glucose target of 80-130 mg/dL provided no incremental benefit in clinical outcome, compared with a more standard approach of serial, subcutaneous insulin injections and a moderate blood glucose target in a multicenter, U.S. trial with more than 1,100 patients.

Mitchel L. Zoler/MDedge News

The results also highlighted the potential downside to aggressive insulin treatment, with an associated 2.6% incidence of severe hypoglycemia, defined as blood glucose falling below 40 mg/dL, Karen C. Johnston, MD, said at the International Stroke Conference sponsored by the American Heart Association.

“Our data suggest that subcutaneously administered insulin with a target blood glucose level of less than 180 mg/dL is the preferred treatment” because it produces similar efficacy without causing any episodes of severe hypoglycemia, concluded Dr. Johnston, professor and chair of neurology at the University of Virginia in Charlottesville. “There should be no further debate” over the potential superiority of a glucose target substantially below 180 mg/dL, she added in an interview.

Continuing to use a glucose target of less than 180 mg/dL and treating patients with subcutaneous insulin injections every 6 hours to achieve this will mean substantially less resource use and precludes the need for keeping patients in intensive care beds as is needed with an insulin drip, Dr. Johnston noted. A treatment target of less than 180 mg/dL is also consistent with the most recent American Heart Association stroke treatment guidelines, which listed a blood glucose target of 140-180 mg/dL as a class IIa recommendation (Stroke. 2018 March;49[3]:e66-99).

The SHINE (Stroke Hyperglycemia Insulin Network Effort) trial enrolled 1,151 adults diagnosed with an acute ischemic stroke at 63 U.S. centers during 2012-2018, excluding patients with type 1 diabetes. Patients had to enter the study within 12 hours of their last known well time, and with an elevated blood glucose level, above 110 mg/dL in patients with type 2 diabetes or at or above 150 mg/dL in other patients. The median glucose level of enrolled patients was about 188 mg/dL. Enrolled patients averaged 66 years old, and about 80% had type 2 diabetes. The median time from last known well to randomization was just over 7 hours. Almost two-thirds of the patients received thrombolytic treatment, and about 13% underwent thrombectomy.

During up to 72 hours of treatment following enrollment the patients in the standard-treatment arm showed a fairly steady average blood glucose level of 179 mg/dL; patients in the intensive arm showed a steady average of 118 mg/dL.

The study’s primary end point was the percentage of patients with a favorable outcome 90 days after enrollment based on their modified Rankin scale score at that time, with the scores that qualified for this end point varying depending on stroke severity at baseline. The percentage of patients achieving this was 20.5% among the intensive patients and 21.6% among those who received standard insulin treatment, a difference that was not statistically significant.

The findings left open the question of how to better manage acute ischemic stroke patients who present with hyperglycemia.

“Hyperglycemic stroke patients have worse outcomes than stroke patients without hyperglycemia. More aggressively treating the hyperglycemia did not help these patients, We need to figure out what will help them,” Dr. Johnson said.

[email protected]

SOURCE: Johnston KC et al. ISC 2019, Abstract LB1.

HONOLULU – In patients who were hyperglycemic following an acute ischemic stroke, intensive insulin control using a continuous insulin drip and an aggressive blood glucose target of 80-130 mg/dL provided no incremental benefit in clinical outcome, compared with a more standard approach of serial, subcutaneous insulin injections and a moderate blood glucose target in a multicenter, U.S. trial with more than 1,100 patients.

Mitchel L. Zoler/MDedge News

The results also highlighted the potential downside to aggressive insulin treatment, with an associated 2.6% incidence of severe hypoglycemia, defined as blood glucose falling below 40 mg/dL, Karen C. Johnston, MD, said at the International Stroke Conference sponsored by the American Heart Association.

“Our data suggest that subcutaneously administered insulin with a target blood glucose level of less than 180 mg/dL is the preferred treatment” because it produces similar efficacy without causing any episodes of severe hypoglycemia, concluded Dr. Johnston, professor and chair of neurology at the University of Virginia in Charlottesville. “There should be no further debate” over the potential superiority of a glucose target substantially below 180 mg/dL, she added in an interview.

Continuing to use a glucose target of less than 180 mg/dL and treating patients with subcutaneous insulin injections every 6 hours to achieve this will mean substantially less resource use and precludes the need for keeping patients in intensive care beds as is needed with an insulin drip, Dr. Johnston noted. A treatment target of less than 180 mg/dL is also consistent with the most recent American Heart Association stroke treatment guidelines, which listed a blood glucose target of 140-180 mg/dL as a class IIa recommendation (Stroke. 2018 March;49[3]:e66-99).

The SHINE (Stroke Hyperglycemia Insulin Network Effort) trial enrolled 1,151 adults diagnosed with an acute ischemic stroke at 63 U.S. centers during 2012-2018, excluding patients with type 1 diabetes. Patients had to enter the study within 12 hours of their last known well time, and with an elevated blood glucose level, above 110 mg/dL in patients with type 2 diabetes or at or above 150 mg/dL in other patients. The median glucose level of enrolled patients was about 188 mg/dL. Enrolled patients averaged 66 years old, and about 80% had type 2 diabetes. The median time from last known well to randomization was just over 7 hours. Almost two-thirds of the patients received thrombolytic treatment, and about 13% underwent thrombectomy.

During up to 72 hours of treatment following enrollment the patients in the standard-treatment arm showed a fairly steady average blood glucose level of 179 mg/dL; patients in the intensive arm showed a steady average of 118 mg/dL.

The study’s primary end point was the percentage of patients with a favorable outcome 90 days after enrollment based on their modified Rankin scale score at that time, with the scores that qualified for this end point varying depending on stroke severity at baseline. The percentage of patients achieving this was 20.5% among the intensive patients and 21.6% among those who received standard insulin treatment, a difference that was not statistically significant.

The findings left open the question of how to better manage acute ischemic stroke patients who present with hyperglycemia.

“Hyperglycemic stroke patients have worse outcomes than stroke patients without hyperglycemia. More aggressively treating the hyperglycemia did not help these patients, We need to figure out what will help them,” Dr. Johnson said.

[email protected]

SOURCE: Johnston KC et al. ISC 2019, Abstract LB1.

BOSTON – An ultra-low-temperature ablation catheter was safe and effective in the first 48 atrial fibrillation (AF) patients to undergo treatment with the device.

Mitchel L. Zoler/MDedge News

The ultra-low-temperature catheter, cooled by liquid nitrogen to –196° C, showed excellent safety and a high success rate, in the modest number of patients who have been followed for 6 or 12 months, Tom De Potter, MD, said at the annual International AF Symposium. The catheter is capable of delivering both focal and linear lesions, said Dr. De Potter, a cardiac electrophysiologist at the Cardiovascular Center of OLV Hospital in Aalst, Belgium.

He reported results on the first 48 AF patients treated with the catheter at either his center or at St. Antonius Hospital in Nieuwegein, the Netherlands, in the CryoCure2 (Investigation of the Adagio Cryoablation System in Patients With Atrial Fibrillation) study. The investigators included safety findings only from the first 13 patients treated, but they assessed both safety and efficacy for the following 35 patients.

The safety review showed one patient with a groin-puncture injury, and two patients with phrenic nerve palsy, but no cases of phrenic nerve palsy in the most recent 41 patients who were treated with an updated version of the catheter that included a cryomapping feature. None of the 48 patients had a stroke, transient ischemic attack, esophageal injury, tamponade, or MI.

The 35 patients reviewed for efficacy included 10 patients with paroxysmal AF and 25 with persistent AF. All five of the paroxysmal AF patients followed for at least 6 months, and all four of those patients followed for 12 months, showed no AF recurrences. One of the persistent AF patients never achieved cardioversion at the time of the ablation procedure. All 17 other persistent AF patients followed for at least 6 months remained in sinus rhythm at 6 months. Among the eight of these patients followed for at least 12 months after treatment, one patient had AF recurrence, so the current 12-month rate of freedom from recurrence is seven of nine patients (including the one who never achieved cardioversion), or 78%.

The average procedure time to perform pulmonary vein isolation (PVI) only was 106 minutes, and procedure time was 116 minutes in the patients who underwent PVI plus additional ablation procedures. Average ablation time was 12 minutes among those just having PVI, and 14 minutes in those who underwent PVI plus other ablations. The cryoablation catheter comes with 20 electrodes that allow it to also record electrograms.

The attraction of the ultra-low-temperature cryoablation catheter used in the study is it “can achieve complete PVI considerably faster” than other ablation methods while also achieving “unsurpassed efficacy,” Dr. De Potter said in a written statement. In addition, “the new, adjustable diagnostic capacity simplifies the procedure and makes it much less operator dependent,” he added.

[email protected]

BOSTON – An ultra-low-temperature ablation catheter was safe and effective in the first 48 atrial fibrillation (AF) patients to undergo treatment with the device.

Mitchel L. Zoler/MDedge News

The ultra-low-temperature catheter, cooled by liquid nitrogen to –196° C, showed excellent safety and a high success rate, in the modest number of patients who have been followed for 6 or 12 months, Tom De Potter, MD, said at the annual International AF Symposium. The catheter is capable of delivering both focal and linear lesions, said Dr. De Potter, a cardiac electrophysiologist at the Cardiovascular Center of OLV Hospital in Aalst, Belgium.

He reported results on the first 48 AF patients treated with the catheter at either his center or at St. Antonius Hospital in Nieuwegein, the Netherlands, in the CryoCure2 (Investigation of the Adagio Cryoablation System in Patients With Atrial Fibrillation) study. The investigators included safety findings only from the first 13 patients treated, but they assessed both safety and efficacy for the following 35 patients.

The safety review showed one patient with a groin-puncture injury, and two patients with phrenic nerve palsy, but no cases of phrenic nerve palsy in the most recent 41 patients who were treated with an updated version of the catheter that included a cryomapping feature. None of the 48 patients had a stroke, transient ischemic attack, esophageal injury, tamponade, or MI.

The 35 patients reviewed for efficacy included 10 patients with paroxysmal AF and 25 with persistent AF. All five of the paroxysmal AF patients followed for at least 6 months, and all four of those patients followed for 12 months, showed no AF recurrences. One of the persistent AF patients never achieved cardioversion at the time of the ablation procedure. All 17 other persistent AF patients followed for at least 6 months remained in sinus rhythm at 6 months. Among the eight of these patients followed for at least 12 months after treatment, one patient had AF recurrence, so the current 12-month rate of freedom from recurrence is seven of nine patients (including the one who never achieved cardioversion), or 78%.

The average procedure time to perform pulmonary vein isolation (PVI) only was 106 minutes, and procedure time was 116 minutes in the patients who underwent PVI plus additional ablation procedures. Average ablation time was 12 minutes among those just having PVI, and 14 minutes in those who underwent PVI plus other ablations. The cryoablation catheter comes with 20 electrodes that allow it to also record electrograms.

The attraction of the ultra-low-temperature cryoablation catheter used in the study is it “can achieve complete PVI considerably faster” than other ablation methods while also achieving “unsurpassed efficacy,” Dr. De Potter said in a written statement. In addition, “the new, adjustable diagnostic capacity simplifies the procedure and makes it much less operator dependent,” he added.

[email protected]

BOSTON – An ultra-low-temperature ablation catheter was safe and effective in the first 48 atrial fibrillation (AF) patients to undergo treatment with the device.

Mitchel L. Zoler/MDedge News

The ultra-low-temperature catheter, cooled by liquid nitrogen to –196° C, showed excellent safety and a high success rate, in the modest number of patients who have been followed for 6 or 12 months, Tom De Potter, MD, said at the annual International AF Symposium. The catheter is capable of delivering both focal and linear lesions, said Dr. De Potter, a cardiac electrophysiologist at the Cardiovascular Center of OLV Hospital in Aalst, Belgium.

He reported results on the first 48 AF patients treated with the catheter at either his center or at St. Antonius Hospital in Nieuwegein, the Netherlands, in the CryoCure2 (Investigation of the Adagio Cryoablation System in Patients With Atrial Fibrillation) study. The investigators included safety findings only from the first 13 patients treated, but they assessed both safety and efficacy for the following 35 patients.

The safety review showed one patient with a groin-puncture injury, and two patients with phrenic nerve palsy, but no cases of phrenic nerve palsy in the most recent 41 patients who were treated with an updated version of the catheter that included a cryomapping feature. None of the 48 patients had a stroke, transient ischemic attack, esophageal injury, tamponade, or MI.

The 35 patients reviewed for efficacy included 10 patients with paroxysmal AF and 25 with persistent AF. All five of the paroxysmal AF patients followed for at least 6 months, and all four of those patients followed for 12 months, showed no AF recurrences. One of the persistent AF patients never achieved cardioversion at the time of the ablation procedure. All 17 other persistent AF patients followed for at least 6 months remained in sinus rhythm at 6 months. Among the eight of these patients followed for at least 12 months after treatment, one patient had AF recurrence, so the current 12-month rate of freedom from recurrence is seven of nine patients (including the one who never achieved cardioversion), or 78%.

The average procedure time to perform pulmonary vein isolation (PVI) only was 106 minutes, and procedure time was 116 minutes in the patients who underwent PVI plus additional ablation procedures. Average ablation time was 12 minutes among those just having PVI, and 14 minutes in those who underwent PVI plus other ablations. The cryoablation catheter comes with 20 electrodes that allow it to also record electrograms.

The attraction of the ultra-low-temperature cryoablation catheter used in the study is it “can achieve complete PVI considerably faster” than other ablation methods while also achieving “unsurpassed efficacy,” Dr. De Potter said in a written statement. In addition, “the new, adjustable diagnostic capacity simplifies the procedure and makes it much less operator dependent,” he added.

[email protected]

Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.

It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.

“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.

“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.

“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”

“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.

Focusing on patients with psoriasis

Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.

“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.

PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.

“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
 

Widening the PsA diagnostic net

What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.

The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.

“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.

“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”

“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.

“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”

Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.

“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
 

The earliest indicators of PsA

Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).

Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).

In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).

These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.

The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)

The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”

Weight loss and other interventions

Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.

Penn Medicine

Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”

“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.

“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.

At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).

Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).

Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.

“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.

Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.

[email protected]

Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.

It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.

“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.

“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.

“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”

“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.

Focusing on patients with psoriasis

Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.

“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.

PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.

“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
 

Widening the PsA diagnostic net

What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.

The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.

“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.

“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”

“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.

“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”

Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.

“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
 

The earliest indicators of PsA

Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).

Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).

In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).

These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.

The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)

The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”

Weight loss and other interventions

Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.

Penn Medicine

Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”

“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.

“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.

At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).

Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).

Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.

“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.

Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.

[email protected]

Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.

It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.

“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.

“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.

“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”

“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.

Focusing on patients with psoriasis

Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.

“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.

PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.

“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
 

Widening the PsA diagnostic net

What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.

The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.

“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.

“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”

“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.

“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”

Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.

“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
 

The earliest indicators of PsA

Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).

Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).

In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).

These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.

The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)

The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”

Weight loss and other interventions

Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.

Penn Medicine

Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”

“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.

“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.

At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).

Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).

Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.

“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.

Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.

[email protected]

BOSTON – Patients with atrial fibrillation who present to emergency departments, despite being asymptomatic, often go based on of their understanding of advice they had previously received from their physicians, according to results from a prospective study of 356 Canadian atrial arrhythmia patients seen in emergency settings.

Mitchel L. Zoler/MDedge News

One way to deal with potentially inappropriate emergency department use is to have concerned patients with atrial fibrillation (AF) record their heart rhythm data with a handheld device or watch, transfer the records to their smartphones, and transmit the information to a remote physician for interpretation and advice, Benedict M. Glover, MD, said at the annual International AF Symposium.

Dr. Glover and his associates are in the process of developing a prototype system of this design to address the need they identified in a recent registry of 356 patients with a primary diagnosis of AF who sought care in the emergency department (ED) of any of seven participating Canadian medical centers, including five academic centers and two community hospitals. The survey results showed that 71% of the patients were symptomatic and 29% were asymptomatic then they first presented to an emergency department.


Case reviews of the 356 patients showed that 152 (43%) came to the EDs for what were classified as inappropriate reasons. The most common cause by far of an inappropriate emergency presentation was prior medical advice the patient had received, cited in 62% of the inappropriate cases, compared with 9% of the appropriate cases, said Dr. Glover, an electrophysiologist at Sunnybrook Health Sciences Centre in Toronto.

The inappropriate ED use by AF patients could be addressed in at least two ways, he said. One solution might be to give patients an alternative destination, so that instead of going to an emergency department they could go to an outpatient AF clinic. A second solution is to give patients a way to have their heart rhythm assessed remotely at the time of their concern. Dr. Glover said that his center had the staff capacity to deal with the potential influx of rhythm data from a pilot-sized program of remote heart-rhythm monitoring, but he conceded that scaling up to deal with the data that could come from the entire panel of AF patients managed by Sunnybrook physicians would be a huge challenge.

“The issue is what do we do with the data after we get it,” Dr. Glover said. “It’s a lot of information.”

Dr. Glover had no disclosures.

[email protected]

BOSTON – Patients with atrial fibrillation who present to emergency departments, despite being asymptomatic, often go based on of their understanding of advice they had previously received from their physicians, according to results from a prospective study of 356 Canadian atrial arrhythmia patients seen in emergency settings.

Mitchel L. Zoler/MDedge News

One way to deal with potentially inappropriate emergency department use is to have concerned patients with atrial fibrillation (AF) record their heart rhythm data with a handheld device or watch, transfer the records to their smartphones, and transmit the information to a remote physician for interpretation and advice, Benedict M. Glover, MD, said at the annual International AF Symposium.

Dr. Glover and his associates are in the process of developing a prototype system of this design to address the need they identified in a recent registry of 356 patients with a primary diagnosis of AF who sought care in the emergency department (ED) of any of seven participating Canadian medical centers, including five academic centers and two community hospitals. The survey results showed that 71% of the patients were symptomatic and 29% were asymptomatic then they first presented to an emergency department.


Case reviews of the 356 patients showed that 152 (43%) came to the EDs for what were classified as inappropriate reasons. The most common cause by far of an inappropriate emergency presentation was prior medical advice the patient had received, cited in 62% of the inappropriate cases, compared with 9% of the appropriate cases, said Dr. Glover, an electrophysiologist at Sunnybrook Health Sciences Centre in Toronto.

The inappropriate ED use by AF patients could be addressed in at least two ways, he said. One solution might be to give patients an alternative destination, so that instead of going to an emergency department they could go to an outpatient AF clinic. A second solution is to give patients a way to have their heart rhythm assessed remotely at the time of their concern. Dr. Glover said that his center had the staff capacity to deal with the potential influx of rhythm data from a pilot-sized program of remote heart-rhythm monitoring, but he conceded that scaling up to deal with the data that could come from the entire panel of AF patients managed by Sunnybrook physicians would be a huge challenge.

“The issue is what do we do with the data after we get it,” Dr. Glover said. “It’s a lot of information.”

Dr. Glover had no disclosures.

[email protected]

BOSTON – Patients with atrial fibrillation who present to emergency departments, despite being asymptomatic, often go based on of their understanding of advice they had previously received from their physicians, according to results from a prospective study of 356 Canadian atrial arrhythmia patients seen in emergency settings.

Mitchel L. Zoler/MDedge News

One way to deal with potentially inappropriate emergency department use is to have concerned patients with atrial fibrillation (AF) record their heart rhythm data with a handheld device or watch, transfer the records to their smartphones, and transmit the information to a remote physician for interpretation and advice, Benedict M. Glover, MD, said at the annual International AF Symposium.

Dr. Glover and his associates are in the process of developing a prototype system of this design to address the need they identified in a recent registry of 356 patients with a primary diagnosis of AF who sought care in the emergency department (ED) of any of seven participating Canadian medical centers, including five academic centers and two community hospitals. The survey results showed that 71% of the patients were symptomatic and 29% were asymptomatic then they first presented to an emergency department.


Case reviews of the 356 patients showed that 152 (43%) came to the EDs for what were classified as inappropriate reasons. The most common cause by far of an inappropriate emergency presentation was prior medical advice the patient had received, cited in 62% of the inappropriate cases, compared with 9% of the appropriate cases, said Dr. Glover, an electrophysiologist at Sunnybrook Health Sciences Centre in Toronto.

The inappropriate ED use by AF patients could be addressed in at least two ways, he said. One solution might be to give patients an alternative destination, so that instead of going to an emergency department they could go to an outpatient AF clinic. A second solution is to give patients a way to have their heart rhythm assessed remotely at the time of their concern. Dr. Glover said that his center had the staff capacity to deal with the potential influx of rhythm data from a pilot-sized program of remote heart-rhythm monitoring, but he conceded that scaling up to deal with the data that could come from the entire panel of AF patients managed by Sunnybrook physicians would be a huge challenge.

“The issue is what do we do with the data after we get it,” Dr. Glover said. “It’s a lot of information.”

Dr. Glover had no disclosures.

[email protected]

BOSTON – An atrial mapping catheter that combines ultrasound anatomic mapping with nontouch, high-resolution, charge-density mapping resulted in a high, 73% freedom from recurrent atrial fibrillation rate 12 months after ablation procedures guided by this catheter in a single-arm, multicenter study with 121 patients with persistent atrial fibrillation followed for 1 year.

Mitchel L. Zoler/MDedge News

The AcQMap device tested in the study “allows you to quickly remap” the left atrium after an initial pulmonary vein isolation or after other types of ablations to find remaining areas of abnormal electrical activity on the atrial walls and then “go after those,” Atul Verma, MD, said at the annual International AF Symposium.

An analysis he reported showed that the single patient variable that linked with the highest rate of 1-year freedom from recurrent atrial fibrillation (AF) was having at least three atrial targets ablated in addition to pulmonary vein isolation. Patients who received this number of added ablations were more than nine times more likely to be free from AF after 12 months, compared with patients who received fewer additional ablations, said Dr. Verma, a cardiac electrophysiologist at Southlake Regional Health Centre in Newmarket, Ont.

The AcQMap catheter “identifies more places to ablate.” What makes it unique among currently available mapping devices is its high resolution, its use of charge-density mapping rather than voltage-based mapping, and its speed, Dr. Verma said in an interview.

The AcQMap device has Food and Drug Administration marketing approval for mapping and so is available for routine U.S. use. However, Dr. Verma cautioned that the increased freedom from persistent AF after using the catheter during ablation that he reported should be confirmed by a randomized trial. Another electrophysiologist who performs ablations but was not involved with the study, Vivek Reddy, MD, agreed with this caveat.

Mitchel L. Zoler/MDedge News

“Nonrandomized trials of ablation in patients with persistent AF are at best hypothesis generating. We’ve learned that the hard way; we have been burned too many times. To assess mapping of AF activity you need a randomized, controlled trial,” said Dr. Reddy, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.

The UNCOVER-AF (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) study ran at 13 centers in Canada and Europe and enrolled 129 patients who had persistent AF for an average of almost 2 years, of whom 127 actually underwent an ablation procedure and 121 were followed for 12 months post ablation. Operators were free to use the AcQMap device to map the left atrium as many times as they thought necessary, generally once at the start of the procedure, a second time after they completed pulmonary vein isolation, and then a variable number of subsequent times. On average they performed about four mappings in each patient. At entry, patients had received an average of one antiarrhythmic drug. After their ablation treatment, about 10% of patients received an antiarrhythmic drug.

The investigators found no major adverse events linked to use of the mapping device. Three patients had major adverse events related to the overall ablation procedure: Two developed cardiac tamponade, and one had a stroke. No patients had an esophageal fistula or symptomatic pulmonary vein stenosis.

After the single ablation procedure and at 12-month follow-up, the prevalence of freedom from recurrent AF was 73%, and freedom from any atrial arrhythmia was 69%. As a historical comparison, Dr. Verma cited the 12-month outcome following pulmonary vein isolation and other ablative measures in the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) trial, which reported a 59% freedom from AF rate and a 49% freedom from any atrial arrhythmia rate with or without antiarrhythmic drug treatment after pulmonary vein isolation (N Engl J Med. 2015 May 7;372[19]:1812-22).

Multivariate analysis of the new data showed that, in addition to ablation of three or more targets, two other variables also linked significantly with long-term freedom from AF: Ablation of at least two types of electrical abnormalities in the left atrial wall, which boosted the 12-month AF-free rate by 2.8 fold, and being in sinus rhythm at the start of the ablation procedure, which linked with a 5-fold higher rate of long-term freedom from AF.

Dr. Verma also reported the AF burden measured after ablation in 96 patients who each underwent an average of 85 hours of postablation heart rhythm monitoring. Ninety percent of these patients showed no AF episodes of more than 30 seconds throughout the duration of their monitoring.

UNCOVER-AF was funded by Acutus, the company that markets the AcQMap catheter. Dr. Verma has been an advisor to or speaker on behalf of Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic, and St. Jude (Abbott), and he has received research funding from Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic. He had no personal disclosures relative to Acutus. Dr. Reddy has been a consultant to, received research funding from, and has an equity stake in Acutus, and has similar relationships with more than three dozen other companies.

[email protected]

BOSTON – An atrial mapping catheter that combines ultrasound anatomic mapping with nontouch, high-resolution, charge-density mapping resulted in a high, 73% freedom from recurrent atrial fibrillation rate 12 months after ablation procedures guided by this catheter in a single-arm, multicenter study with 121 patients with persistent atrial fibrillation followed for 1 year.

Mitchel L. Zoler/MDedge News

The AcQMap device tested in the study “allows you to quickly remap” the left atrium after an initial pulmonary vein isolation or after other types of ablations to find remaining areas of abnormal electrical activity on the atrial walls and then “go after those,” Atul Verma, MD, said at the annual International AF Symposium.

An analysis he reported showed that the single patient variable that linked with the highest rate of 1-year freedom from recurrent atrial fibrillation (AF) was having at least three atrial targets ablated in addition to pulmonary vein isolation. Patients who received this number of added ablations were more than nine times more likely to be free from AF after 12 months, compared with patients who received fewer additional ablations, said Dr. Verma, a cardiac electrophysiologist at Southlake Regional Health Centre in Newmarket, Ont.

The AcQMap catheter “identifies more places to ablate.” What makes it unique among currently available mapping devices is its high resolution, its use of charge-density mapping rather than voltage-based mapping, and its speed, Dr. Verma said in an interview.

The AcQMap device has Food and Drug Administration marketing approval for mapping and so is available for routine U.S. use. However, Dr. Verma cautioned that the increased freedom from persistent AF after using the catheter during ablation that he reported should be confirmed by a randomized trial. Another electrophysiologist who performs ablations but was not involved with the study, Vivek Reddy, MD, agreed with this caveat.

Mitchel L. Zoler/MDedge News

“Nonrandomized trials of ablation in patients with persistent AF are at best hypothesis generating. We’ve learned that the hard way; we have been burned too many times. To assess mapping of AF activity you need a randomized, controlled trial,” said Dr. Reddy, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.

The UNCOVER-AF (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) study ran at 13 centers in Canada and Europe and enrolled 129 patients who had persistent AF for an average of almost 2 years, of whom 127 actually underwent an ablation procedure and 121 were followed for 12 months post ablation. Operators were free to use the AcQMap device to map the left atrium as many times as they thought necessary, generally once at the start of the procedure, a second time after they completed pulmonary vein isolation, and then a variable number of subsequent times. On average they performed about four mappings in each patient. At entry, patients had received an average of one antiarrhythmic drug. After their ablation treatment, about 10% of patients received an antiarrhythmic drug.

The investigators found no major adverse events linked to use of the mapping device. Three patients had major adverse events related to the overall ablation procedure: Two developed cardiac tamponade, and one had a stroke. No patients had an esophageal fistula or symptomatic pulmonary vein stenosis.

After the single ablation procedure and at 12-month follow-up, the prevalence of freedom from recurrent AF was 73%, and freedom from any atrial arrhythmia was 69%. As a historical comparison, Dr. Verma cited the 12-month outcome following pulmonary vein isolation and other ablative measures in the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) trial, which reported a 59% freedom from AF rate and a 49% freedom from any atrial arrhythmia rate with or without antiarrhythmic drug treatment after pulmonary vein isolation (N Engl J Med. 2015 May 7;372[19]:1812-22).

Multivariate analysis of the new data showed that, in addition to ablation of three or more targets, two other variables also linked significantly with long-term freedom from AF: Ablation of at least two types of electrical abnormalities in the left atrial wall, which boosted the 12-month AF-free rate by 2.8 fold, and being in sinus rhythm at the start of the ablation procedure, which linked with a 5-fold higher rate of long-term freedom from AF.

Dr. Verma also reported the AF burden measured after ablation in 96 patients who each underwent an average of 85 hours of postablation heart rhythm monitoring. Ninety percent of these patients showed no AF episodes of more than 30 seconds throughout the duration of their monitoring.

UNCOVER-AF was funded by Acutus, the company that markets the AcQMap catheter. Dr. Verma has been an advisor to or speaker on behalf of Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic, and St. Jude (Abbott), and he has received research funding from Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic. He had no personal disclosures relative to Acutus. Dr. Reddy has been a consultant to, received research funding from, and has an equity stake in Acutus, and has similar relationships with more than three dozen other companies.

[email protected]

BOSTON – An atrial mapping catheter that combines ultrasound anatomic mapping with nontouch, high-resolution, charge-density mapping resulted in a high, 73% freedom from recurrent atrial fibrillation rate 12 months after ablation procedures guided by this catheter in a single-arm, multicenter study with 121 patients with persistent atrial fibrillation followed for 1 year.

Mitchel L. Zoler/MDedge News

The AcQMap device tested in the study “allows you to quickly remap” the left atrium after an initial pulmonary vein isolation or after other types of ablations to find remaining areas of abnormal electrical activity on the atrial walls and then “go after those,” Atul Verma, MD, said at the annual International AF Symposium.

An analysis he reported showed that the single patient variable that linked with the highest rate of 1-year freedom from recurrent atrial fibrillation (AF) was having at least three atrial targets ablated in addition to pulmonary vein isolation. Patients who received this number of added ablations were more than nine times more likely to be free from AF after 12 months, compared with patients who received fewer additional ablations, said Dr. Verma, a cardiac electrophysiologist at Southlake Regional Health Centre in Newmarket, Ont.

The AcQMap catheter “identifies more places to ablate.” What makes it unique among currently available mapping devices is its high resolution, its use of charge-density mapping rather than voltage-based mapping, and its speed, Dr. Verma said in an interview.

The AcQMap device has Food and Drug Administration marketing approval for mapping and so is available for routine U.S. use. However, Dr. Verma cautioned that the increased freedom from persistent AF after using the catheter during ablation that he reported should be confirmed by a randomized trial. Another electrophysiologist who performs ablations but was not involved with the study, Vivek Reddy, MD, agreed with this caveat.

Mitchel L. Zoler/MDedge News

“Nonrandomized trials of ablation in patients with persistent AF are at best hypothesis generating. We’ve learned that the hard way; we have been burned too many times. To assess mapping of AF activity you need a randomized, controlled trial,” said Dr. Reddy, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.

The UNCOVER-AF (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) study ran at 13 centers in Canada and Europe and enrolled 129 patients who had persistent AF for an average of almost 2 years, of whom 127 actually underwent an ablation procedure and 121 were followed for 12 months post ablation. Operators were free to use the AcQMap device to map the left atrium as many times as they thought necessary, generally once at the start of the procedure, a second time after they completed pulmonary vein isolation, and then a variable number of subsequent times. On average they performed about four mappings in each patient. At entry, patients had received an average of one antiarrhythmic drug. After their ablation treatment, about 10% of patients received an antiarrhythmic drug.

The investigators found no major adverse events linked to use of the mapping device. Three patients had major adverse events related to the overall ablation procedure: Two developed cardiac tamponade, and one had a stroke. No patients had an esophageal fistula or symptomatic pulmonary vein stenosis.

After the single ablation procedure and at 12-month follow-up, the prevalence of freedom from recurrent AF was 73%, and freedom from any atrial arrhythmia was 69%. As a historical comparison, Dr. Verma cited the 12-month outcome following pulmonary vein isolation and other ablative measures in the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) trial, which reported a 59% freedom from AF rate and a 49% freedom from any atrial arrhythmia rate with or without antiarrhythmic drug treatment after pulmonary vein isolation (N Engl J Med. 2015 May 7;372[19]:1812-22).

Multivariate analysis of the new data showed that, in addition to ablation of three or more targets, two other variables also linked significantly with long-term freedom from AF: Ablation of at least two types of electrical abnormalities in the left atrial wall, which boosted the 12-month AF-free rate by 2.8 fold, and being in sinus rhythm at the start of the ablation procedure, which linked with a 5-fold higher rate of long-term freedom from AF.

Dr. Verma also reported the AF burden measured after ablation in 96 patients who each underwent an average of 85 hours of postablation heart rhythm monitoring. Ninety percent of these patients showed no AF episodes of more than 30 seconds throughout the duration of their monitoring.

UNCOVER-AF was funded by Acutus, the company that markets the AcQMap catheter. Dr. Verma has been an advisor to or speaker on behalf of Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic, and St. Jude (Abbott), and he has received research funding from Bayer, Biosense Webster, Boehringer Ingelheim, and Medtronic. He had no personal disclosures relative to Acutus. Dr. Reddy has been a consultant to, received research funding from, and has an equity stake in Acutus, and has similar relationships with more than three dozen other companies.

[email protected]

The first update to U.S. medical-society guidelines for managing atrial fibrillation since 2014 raised the threshold for starting anticoagulant therapy in women, pegged the direct-acting oral anticoagulants (DOACs) as preferred over warfarin, and introduced for the first time weight loss as an important intervention tool for treating patients with an atrial arrhythmia.

Mitchel L. Zoler/MDedge News

On January 28, the American College of Cardiology, American Heart Association, and Heart Rhythm Society posted online a 2019 focused update (Circulation. 2019 Jan 28. doi: 10.1161/CIR.0000000000000665) to the 2014 atrial fibrillation (AF) management guidelines that the groups had previously published (J Am Coll Cardiol. 2014 Dec 2;64[21]:2246-80).

Perhaps the two most important changes, as well as the two that lead off the new document, were a pair of class I recommendations on using oral anticoagulation in AF patients.

One of these updates reset the threshold for initiating oral anticoagulant therapy in women from 2 points on the CHA2DS2-VASc scale to 3 points, while leaving the threshold for men unchanged at 2 points. This brought U.S. guidelines in line with European guidelines, set by the European Society of Cardiology in 2016 (Eur Heart J. 2016 Oct 7;37[38]:2893-962). It will now also mean that, because of the way the CHA2DS2-VASc score is calculated, women with AF who are at least 65 years old will no longer automatically get flagged as needing oral anticoagulant therapy.

“This is a really important shift. It’s recognition that female sex is not as important a risk factor [for AF-associated stroke] as once was thought,” commented Hugh Calkins, MD, professor of medicine at Johns Hopkins Medicine in Baltimore and a member of the panel that wrote the update. “This will change the number of women with AF who go on anticoagulation,” predicted Dr. Calkins, who directs the cardiac arrhythmia service at his center. “We have been struggling with the notion that all women 65 or older with AF had to be on an anticoagulant. Now a clinician has more leeway. In general, patients with AF remain underanticoagulated, but this clarifies practice and brings us in line with the European guidelines.”

The second important change to the anticoagulation recommendations was to specify the DOACs as recommended over warfarin in AF patients eligible for oral anticoagulation and without moderate to severe mitral stenosis or a mechanical heart valve, which also matches the 2016 European guidelines and updates the prior, 2014, U.S. guidelines, which didn’t even mention DOACs.

Prescribing a DOAC preferentially to AF patients has already become routine among electrophysiologists, but possibly not as routine among primary care physicians, so this change has the potential to shift practice, said Dr. Calkins. But the higher price for DOACs, compared with warfarin, can pose problems. “The cost of DOACs remains an issue that can be a serious limitation to some patients,” said Craig T. January, MD, professor of medicine at the University of Wisconsin in Madison and chair of the guideline-writing panel. He also bemoaned the absence of head-to-head comparisons of individual DOACs that could inform selecting among apixaban, dabigatran, edoxaban, and rivaroxaban.

Another notable change in the 2019 update was inclusion for the first time of weight loss as a recommended intervention, along with other risk factor modification, an addition that Dr. Calkins called “long overdue.”

Mitchel L. Zoler/MDedge News

“This is a new recommendation, and it will potentially be important,” said Dr. January, although the guidelines do not spell out how aggressive clinicians should be about having patients achieve weight loss, how much loss patients should achieve, or how they should do it. “There are a lot of observational data and basic science data suggesting the importance of weight loss. Most electrophysiologists already address weight loss. The problem is how to get patients to do it,” commented Vivek Reddy, MD, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.

Dr. Reddy expressed surprise over two other features of the updated guidelines. For the first time, the guidelines now address percutaneous left atrial appendage (LAA) occlusion and say: “Percutaneous LAA occlusion may be considered in patients with AF at increased risk of stroke who have contraindications to long-term anticoagulation.” The guidelines’ text acknowledges that this runs counter to the Food and Drug Administration labeling for the Watchman LAA occlusion device, which restricts the device to patients “deemed suitable for long-term warfarin (mirroring the inclusion criteria for enrollment in the clinical trials) but had an appropriate rationale to seek a nonpharmacological alternative to warfarin.”

“We do not take a position on the FDA’s” actions, Dr. January said in an interview.

“The ACC, AHA, and HRS guidelines should reflect what the FDA decided,” Dr. Reddy said in an interview. “I’m a little surprised the guidelines said that anticoagulation had to be contraindicated.

The 2019 update also added a class IIb, “may be reasonable” recommendation for catheter ablation of AF in patients with heart failure with reduced ejection fraction.

“I think a IIb recommendation is unfair; I think it should be a IIa recommendation because there have been positive results from two large, randomized, multicenter trials – CASTLE-AF [Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF; N Engl J Med. 2018 Feb 1;378(5):417-27] and AATAC [Ablation vs Amiodarone for Treatment of AFib in Patients With CHF and an ICD; Circulation. 2016 Apr 26;133(7):1637-44], as well as positive results from several smaller randomized studies,” Dr. Reddy said. “I’m really surprised” that the recommendation was not stronger.

Dr. Calkins has been a consultant to Abbott, Altathera, AtriCare, Boehringer-Ingelheim, King, Medtronic, and St. Jude and has received research funding from Boehringer-Ingelheim, Boston Scientific, and St. Jude. Dr. January had no disclosures. Dr. Reddy has been a consultant to, received research funding from, or has an equity interest in more than three dozen companies.

[email protected]

The first update to U.S. medical-society guidelines for managing atrial fibrillation since 2014 raised the threshold for starting anticoagulant therapy in women, pegged the direct-acting oral anticoagulants (DOACs) as preferred over warfarin, and introduced for the first time weight loss as an important intervention tool for treating patients with an atrial arrhythmia.

Mitchel L. Zoler/MDedge News

On January 28, the American College of Cardiology, American Heart Association, and Heart Rhythm Society posted online a 2019 focused update (Circulation. 2019 Jan 28. doi: 10.1161/CIR.0000000000000665) to the 2014 atrial fibrillation (AF) management guidelines that the groups had previously published (J Am Coll Cardiol. 2014 Dec 2;64[21]:2246-80).

Perhaps the two most important changes, as well as the two that lead off the new document, were a pair of class I recommendations on using oral anticoagulation in AF patients.

One of these updates reset the threshold for initiating oral anticoagulant therapy in women from 2 points on the CHA2DS2-VASc scale to 3 points, while leaving the threshold for men unchanged at 2 points. This brought U.S. guidelines in line with European guidelines, set by the European Society of Cardiology in 2016 (Eur Heart J. 2016 Oct 7;37[38]:2893-962). It will now also mean that, because of the way the CHA2DS2-VASc score is calculated, women with AF who are at least 65 years old will no longer automatically get flagged as needing oral anticoagulant therapy.

“This is a really important shift. It’s recognition that female sex is not as important a risk factor [for AF-associated stroke] as once was thought,” commented Hugh Calkins, MD, professor of medicine at Johns Hopkins Medicine in Baltimore and a member of the panel that wrote the update. “This will change the number of women with AF who go on anticoagulation,” predicted Dr. Calkins, who directs the cardiac arrhythmia service at his center. “We have been struggling with the notion that all women 65 or older with AF had to be on an anticoagulant. Now a clinician has more leeway. In general, patients with AF remain underanticoagulated, but this clarifies practice and brings us in line with the European guidelines.”

The second important change to the anticoagulation recommendations was to specify the DOACs as recommended over warfarin in AF patients eligible for oral anticoagulation and without moderate to severe mitral stenosis or a mechanical heart valve, which also matches the 2016 European guidelines and updates the prior, 2014, U.S. guidelines, which didn’t even mention DOACs.

Prescribing a DOAC preferentially to AF patients has already become routine among electrophysiologists, but possibly not as routine among primary care physicians, so this change has the potential to shift practice, said Dr. Calkins. But the higher price for DOACs, compared with warfarin, can pose problems. “The cost of DOACs remains an issue that can be a serious limitation to some patients,” said Craig T. January, MD, professor of medicine at the University of Wisconsin in Madison and chair of the guideline-writing panel. He also bemoaned the absence of head-to-head comparisons of individual DOACs that could inform selecting among apixaban, dabigatran, edoxaban, and rivaroxaban.

Another notable change in the 2019 update was inclusion for the first time of weight loss as a recommended intervention, along with other risk factor modification, an addition that Dr. Calkins called “long overdue.”

Mitchel L. Zoler/MDedge News

“This is a new recommendation, and it will potentially be important,” said Dr. January, although the guidelines do not spell out how aggressive clinicians should be about having patients achieve weight loss, how much loss patients should achieve, or how they should do it. “There are a lot of observational data and basic science data suggesting the importance of weight loss. Most electrophysiologists already address weight loss. The problem is how to get patients to do it,” commented Vivek Reddy, MD, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.

Dr. Reddy expressed surprise over two other features of the updated guidelines. For the first time, the guidelines now address percutaneous left atrial appendage (LAA) occlusion and say: “Percutaneous LAA occlusion may be considered in patients with AF at increased risk of stroke who have contraindications to long-term anticoagulation.” The guidelines’ text acknowledges that this runs counter to the Food and Drug Administration labeling for the Watchman LAA occlusion device, which restricts the device to patients “deemed suitable for long-term warfarin (mirroring the inclusion criteria for enrollment in the clinical trials) but had an appropriate rationale to seek a nonpharmacological alternative to warfarin.”

“We do not take a position on the FDA’s” actions, Dr. January said in an interview.

“The ACC, AHA, and HRS guidelines should reflect what the FDA decided,” Dr. Reddy said in an interview. “I’m a little surprised the guidelines said that anticoagulation had to be contraindicated.

The 2019 update also added a class IIb, “may be reasonable” recommendation for catheter ablation of AF in patients with heart failure with reduced ejection fraction.

“I think a IIb recommendation is unfair; I think it should be a IIa recommendation because there have been positive results from two large, randomized, multicenter trials – CASTLE-AF [Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF; N Engl J Med. 2018 Feb 1;378(5):417-27] and AATAC [Ablation vs Amiodarone for Treatment of AFib in Patients With CHF and an ICD; Circulation. 2016 Apr 26;133(7):1637-44], as well as positive results from several smaller randomized studies,” Dr. Reddy said. “I’m really surprised” that the recommendation was not stronger.

Dr. Calkins has been a consultant to Abbott, Altathera, AtriCare, Boehringer-Ingelheim, King, Medtronic, and St. Jude and has received research funding from Boehringer-Ingelheim, Boston Scientific, and St. Jude. Dr. January had no disclosures. Dr. Reddy has been a consultant to, received research funding from, or has an equity interest in more than three dozen companies.

[email protected]

The first update to U.S. medical-society guidelines for managing atrial fibrillation since 2014 raised the threshold for starting anticoagulant therapy in women, pegged the direct-acting oral anticoagulants (DOACs) as preferred over warfarin, and introduced for the first time weight loss as an important intervention tool for treating patients with an atrial arrhythmia.

Mitchel L. Zoler/MDedge News

On January 28, the American College of Cardiology, American Heart Association, and Heart Rhythm Society posted online a 2019 focused update (Circulation. 2019 Jan 28. doi: 10.1161/CIR.0000000000000665) to the 2014 atrial fibrillation (AF) management guidelines that the groups had previously published (J Am Coll Cardiol. 2014 Dec 2;64[21]:2246-80).

Perhaps the two most important changes, as well as the two that lead off the new document, were a pair of class I recommendations on using oral anticoagulation in AF patients.

One of these updates reset the threshold for initiating oral anticoagulant therapy in women from 2 points on the CHA2DS2-VASc scale to 3 points, while leaving the threshold for men unchanged at 2 points. This brought U.S. guidelines in line with European guidelines, set by the European Society of Cardiology in 2016 (Eur Heart J. 2016 Oct 7;37[38]:2893-962). It will now also mean that, because of the way the CHA2DS2-VASc score is calculated, women with AF who are at least 65 years old will no longer automatically get flagged as needing oral anticoagulant therapy.

“This is a really important shift. It’s recognition that female sex is not as important a risk factor [for AF-associated stroke] as once was thought,” commented Hugh Calkins, MD, professor of medicine at Johns Hopkins Medicine in Baltimore and a member of the panel that wrote the update. “This will change the number of women with AF who go on anticoagulation,” predicted Dr. Calkins, who directs the cardiac arrhythmia service at his center. “We have been struggling with the notion that all women 65 or older with AF had to be on an anticoagulant. Now a clinician has more leeway. In general, patients with AF remain underanticoagulated, but this clarifies practice and brings us in line with the European guidelines.”

The second important change to the anticoagulation recommendations was to specify the DOACs as recommended over warfarin in AF patients eligible for oral anticoagulation and without moderate to severe mitral stenosis or a mechanical heart valve, which also matches the 2016 European guidelines and updates the prior, 2014, U.S. guidelines, which didn’t even mention DOACs.

Prescribing a DOAC preferentially to AF patients has already become routine among electrophysiologists, but possibly not as routine among primary care physicians, so this change has the potential to shift practice, said Dr. Calkins. But the higher price for DOACs, compared with warfarin, can pose problems. “The cost of DOACs remains an issue that can be a serious limitation to some patients,” said Craig T. January, MD, professor of medicine at the University of Wisconsin in Madison and chair of the guideline-writing panel. He also bemoaned the absence of head-to-head comparisons of individual DOACs that could inform selecting among apixaban, dabigatran, edoxaban, and rivaroxaban.

Another notable change in the 2019 update was inclusion for the first time of weight loss as a recommended intervention, along with other risk factor modification, an addition that Dr. Calkins called “long overdue.”

Mitchel L. Zoler/MDedge News

“This is a new recommendation, and it will potentially be important,” said Dr. January, although the guidelines do not spell out how aggressive clinicians should be about having patients achieve weight loss, how much loss patients should achieve, or how they should do it. “There are a lot of observational data and basic science data suggesting the importance of weight loss. Most electrophysiologists already address weight loss. The problem is how to get patients to do it,” commented Vivek Reddy, MD, professor of medicine and director of cardiac arrhythmia services at Mount Sinai Hospital in New York.

Dr. Reddy expressed surprise over two other features of the updated guidelines. For the first time, the guidelines now address percutaneous left atrial appendage (LAA) occlusion and say: “Percutaneous LAA occlusion may be considered in patients with AF at increased risk of stroke who have contraindications to long-term anticoagulation.” The guidelines’ text acknowledges that this runs counter to the Food and Drug Administration labeling for the Watchman LAA occlusion device, which restricts the device to patients “deemed suitable for long-term warfarin (mirroring the inclusion criteria for enrollment in the clinical trials) but had an appropriate rationale to seek a nonpharmacological alternative to warfarin.”

“We do not take a position on the FDA’s” actions, Dr. January said in an interview.

“The ACC, AHA, and HRS guidelines should reflect what the FDA decided,” Dr. Reddy said in an interview. “I’m a little surprised the guidelines said that anticoagulation had to be contraindicated.

The 2019 update also added a class IIb, “may be reasonable” recommendation for catheter ablation of AF in patients with heart failure with reduced ejection fraction.

“I think a IIb recommendation is unfair; I think it should be a IIa recommendation because there have been positive results from two large, randomized, multicenter trials – CASTLE-AF [Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF; N Engl J Med. 2018 Feb 1;378(5):417-27] and AATAC [Ablation vs Amiodarone for Treatment of AFib in Patients With CHF and an ICD; Circulation. 2016 Apr 26;133(7):1637-44], as well as positive results from several smaller randomized studies,” Dr. Reddy said. “I’m really surprised” that the recommendation was not stronger.

Dr. Calkins has been a consultant to Abbott, Altathera, AtriCare, Boehringer-Ingelheim, King, Medtronic, and St. Jude and has received research funding from Boehringer-Ingelheim, Boston Scientific, and St. Jude. Dr. January had no disclosures. Dr. Reddy has been a consultant to, received research funding from, or has an equity interest in more than three dozen companies.

[email protected]

BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.

Mitchel L. Zoler/MDedge News

“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.

Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.

Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.

The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.

Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.

During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.

At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.

A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).

[email protected]

BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.

Mitchel L. Zoler/MDedge News

“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.

Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.

Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.

The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.

Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.

During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.

At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.

A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).

[email protected]

BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.

Mitchel L. Zoler/MDedge News

“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.

Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.

Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.

The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.

Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.

During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.

At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.

A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).

[email protected]