In a small randomized trial, the reduction in recurrence of frequent episodes and demonstrable asystole among older adults was significant. Neurocardiogenic syncope (NCS), the most prevalent form of syncope, typically affects young individuals and is generally benign. However, its clinical progression varies widely, posing challenges in making therapeutic decisions and designing clinical trials. The findings of ISSUE-3, a manufacturer-sponsored, blinded, multicenter, European randomized trial on pacing for NCS, have been recently published.

The study focused on patients aged 40 and above who had experienced three or more NCS episodes in the preceding two years. In a 12-month screening phase before the study, 511 patients received implantable loop recorders. Among them, 77 individuals exhibited syncope and asystole lasting 3 seconds or more or asymptomatic asystolic pauses lasting 6 seconds or more during follow-up. These patients received pacemakers and were randomly assigned to either pacing-on or pacing-off groups. The pacing-off group had a 2-year syncope recurrence rate of 57%, while the pacing-on group had a significantly lower rate of 25% (P=0.04).

According to the study’s findings, pacemakers appear to be effective in a specific subset of older patients with severe neurocardiogenic syncope and asystole. This aligns with the observation that older NCS patients are more likely to have concurrent sinus node dysfunction, making them potential beneficiaries of pacing. However, it’s crucial to exercise caution, as emphasized by an editorialist, and not extend the use of pacing to the entire NCS patient population. The most appropriate candidates for this treatment are those with predominantly asystolic variants, particularly when combined with sinus node dysfunction.

To wrap up

In conclusion, the results of the ISSUE-3 randomized trial shed light on the potential effectiveness of pacemakers in managing a specific group of older patients grappling with severe neurocardiogenic syncope (NCS) and asystole. This study underscores the nuanced nature of NCS, a condition that predominantly affects younger individuals but exhibits a highly variable clinical course.

• The significant reduction in syncope recurrence observed in the pacing-on group compared to the pacing-off group is a promising development. This finding suggests that older NCS patients, particularly those with concurrent sinus node dysfunction, may benefit from pacemaker treatment. These results align with clinical observations that older individuals with NCS often present with more complex cardiac issues, making them prime candidates for pacing therapy;

• However, it’s imperative to exercise caution and avoid broad generalizations. Pacing should not be viewed as a universal solution for all NCS patients. Instead, it appears most beneficial for those with predominantly asystolic variants, especially when coupled with sinus node dysfunction.

In essence, the ISSUE-3 trial provides valuable insights into the management of NCS, particularly in older adults. It underscores the need for individualized approaches and careful patient selection when considering pacing as a potential therapeutic option. Further research and clinical evaluation are warranted to refine the criteria for identifying the most suitable candidates for this intervention within the NCS patient population.