ACC: Patient selection may be the ISSUE with syncope events
CHICAGO—Dual-chamber permanent pacing can effectively reduce syncope events in patients with neurally mediated syncope who are over the age of 40, according to a late-breaking clinical trial presented March 26 at the 61st annual American College of Cardiology (ACC) scientific session. In fact, one out of three patients could benefit from pacemaker therapy to telp thwart syncope events.
"The design is different from other randomized trials because it consists of two phases,” the study’s lead investigator Michele Brignole, MD, head of cardiology at the Arrhythmologic Centre, Ospedali Tigullio in Lavagna, Genoa, told Cardiovascular Business in an interview. The two phases were a screening phase (Phase I) and the randomized trial (Phase II).
“The difference of this trial compared with the vast majority of other trials is the screening phase which is necessary in order to identify the patient who could benefit from a pacemaker,” said Brignole. “We started 10 years back with ISSUE 1 where we evaluated the diagnostic efficacy of an implantable loop recorder [ILR] in patients with unexplained syncope.”
ISSUE 2, was an observational trial that aimed to assess the exit mechanism of electric syncope with an electrocardiogram. “What we found, and it wasn’t so surprising, was that the mechanism of syncope is heterogenous with about half of the patients having longer pauses at the time of syncope,” Brignole said during the interview.
The current ISSUE 3 (International Study on Syncope of Uncertain Etiology 3) trial took place at 51 centers and enrolled 511 patients over an age of 40 who had experienced three or more neurally mediated synope (NMS) in the previous three years. The device used to diagnose the syncope was the Reveal Insertable Cardiac Monitor (Medtronic).
The researchers assessed the cause of a patient’s fainting spells via the ILR. Of the 511 patients, 77 experienced spontaneous asystolic syncope and were implanted with a pacemaker randomly selected to the “on” or “off” position.
Brignole recalled two failed studies, including the VPS II in Canada, which both aimed to study whether the pacemaker was efficacious in patients with syncope. However, Brignole said that these two studies failed to show pacemaker benefit in patients suffering from NMS. “The reason for the negative, or at least not positive results, from these two trials was not that the pacemaker was enabled to prevent syncope, but that the patients were not selected properly."
ISSUE 3 looked to establish the importance of patient selection during pacemaker implantation. The results showed that 57 percent of patients who had the pacemaker set to the “off” position experienced syncope compared with only 25 percent of the patients with an activated pacemaker that suffered syncope.
“This is the first randomized, double-blind trial that definitely shows the efficacy of pacing in patients with electric syncope and systole at time of syncope,” Brignole offered.
The researchers found that one in three pacemaker patients benefit from pacing therapy within two years. Additionally, they noted that dual-chamber permanent pacing is effective to reduce recurrence of syncope in patients over the age of 40 years with severe asytolic NMS.
“Many, many cardiologists were skeptical about the usefulness of pacemakers in this population,” Brignole offered. “The results of ISSUE 3 now definitely prove that pacing is effective especially when the right patients are selected.”
So, how do you select the right patient? “Other selection criteria are those suggested by the syncope guidelines put forth by the European Society of Cardiology," Brignole offered
“This can be summarized in a short sentence,” he noted. The patient must have: severe presentation that requires treatment; be over the age of 40; have three of more syncope events within the last three years; and unpredictable syncope, he said.
“A small subset of the vast population with syncope that can benefit from an invasive therapy such as a pacemaker,” Brignole concluded.
“Syncope is very common in the general population,” he said. “More than one of four have at least one fainting spell during their lifetime and of course you cannot have a pacemaker implanted in all of these people. The easiest solution is proper patient selection, otherwise the procedure may not be all that effective or accepted by physicians and patients.
“We have estimated that only 9 percent of all the patients affected by syncope will receive implantable loop recorder,” Brignole said. “We will need to wait up to 40 years in order to identify all the patients who will benefit on pacemaker and this is only about half of the patients.” Lastly, Brignole noted that 18 percent of patients receiving an ILR will be candidates for a pacemaker within one year, while 40 percent will become candidates for a pacemaker within four years.
"The design is different from other randomized trials because it consists of two phases,” the study’s lead investigator Michele Brignole, MD, head of cardiology at the Arrhythmologic Centre, Ospedali Tigullio in Lavagna, Genoa, told Cardiovascular Business in an interview. The two phases were a screening phase (Phase I) and the randomized trial (Phase II).
“The difference of this trial compared with the vast majority of other trials is the screening phase which is necessary in order to identify the patient who could benefit from a pacemaker,” said Brignole. “We started 10 years back with ISSUE 1 where we evaluated the diagnostic efficacy of an implantable loop recorder [ILR] in patients with unexplained syncope.”
ISSUE 2, was an observational trial that aimed to assess the exit mechanism of electric syncope with an electrocardiogram. “What we found, and it wasn’t so surprising, was that the mechanism of syncope is heterogenous with about half of the patients having longer pauses at the time of syncope,” Brignole said during the interview.
The current ISSUE 3 (International Study on Syncope of Uncertain Etiology 3) trial took place at 51 centers and enrolled 511 patients over an age of 40 who had experienced three or more neurally mediated synope (NMS) in the previous three years. The device used to diagnose the syncope was the Reveal Insertable Cardiac Monitor (Medtronic).
The researchers assessed the cause of a patient’s fainting spells via the ILR. Of the 511 patients, 77 experienced spontaneous asystolic syncope and were implanted with a pacemaker randomly selected to the “on” or “off” position.
Brignole recalled two failed studies, including the VPS II in Canada, which both aimed to study whether the pacemaker was efficacious in patients with syncope. However, Brignole said that these two studies failed to show pacemaker benefit in patients suffering from NMS. “The reason for the negative, or at least not positive results, from these two trials was not that the pacemaker was enabled to prevent syncope, but that the patients were not selected properly."
ISSUE 3 looked to establish the importance of patient selection during pacemaker implantation. The results showed that 57 percent of patients who had the pacemaker set to the “off” position experienced syncope compared with only 25 percent of the patients with an activated pacemaker that suffered syncope.
“This is the first randomized, double-blind trial that definitely shows the efficacy of pacing in patients with electric syncope and systole at time of syncope,” Brignole offered.
The researchers found that one in three pacemaker patients benefit from pacing therapy within two years. Additionally, they noted that dual-chamber permanent pacing is effective to reduce recurrence of syncope in patients over the age of 40 years with severe asytolic NMS.
“Many, many cardiologists were skeptical about the usefulness of pacemakers in this population,” Brignole offered. “The results of ISSUE 3 now definitely prove that pacing is effective especially when the right patients are selected.”
So, how do you select the right patient? “Other selection criteria are those suggested by the syncope guidelines put forth by the European Society of Cardiology," Brignole offered
“This can be summarized in a short sentence,” he noted. The patient must have: severe presentation that requires treatment; be over the age of 40; have three of more syncope events within the last three years; and unpredictable syncope, he said.
“A small subset of the vast population with syncope that can benefit from an invasive therapy such as a pacemaker,” Brignole concluded.
“Syncope is very common in the general population,” he said. “More than one of four have at least one fainting spell during their lifetime and of course you cannot have a pacemaker implanted in all of these people. The easiest solution is proper patient selection, otherwise the procedure may not be all that effective or accepted by physicians and patients.
“We have estimated that only 9 percent of all the patients affected by syncope will receive implantable loop recorder,” Brignole said. “We will need to wait up to 40 years in order to identify all the patients who will benefit on pacemaker and this is only about half of the patients.” Lastly, Brignole noted that 18 percent of patients receiving an ILR will be candidates for a pacemaker within one year, while 40 percent will become candidates for a pacemaker within four years.