Effects of caRdioneurOablation on Exercise perforMance in Patients With Reflex Asystolic syNcope: The Roman 3 Study

Introduction Cardioneuroablation (CNA) is a new promising method to treat reflex syncope which is due to vagally-induced functional sinus arrest or atrio-ventricular block (AVB). The goal of the procedure is to ablate post-ganglionic endings of the parasympathetic part of the autonomic nervous system (ANS), located in ganglionated plexi (GP) in the epicardial fat and in the myocardium. Although both sympathetic and parasympathetic nerves are localized in GPs, the latter ones only barely regenerate. Therefore, CNA-induced damage to the parasympathetic part of GP is greater and more durable than that of the sympathetic part of ANS. Because increased vagal activity is one of the main mechanisms leading to reflex sinus arrest or atrio-ventricular (AV) block, targeting this part of ANS by CNA may prevent recurrences of reflex syncope. Indeed, it has been shown that CNA may be effective in approximately 80-90% of very symptomatic subjects with reflex syncope.

Lack or diminished parasympathetic drive to the heart may be, however, associated with adverse effects. The main complication which is seen shortly and up to one year after CNA is heart rhythm acceleration which may be symptomatic in approximately one-third of patients. In the majority of patients sinus rate gradually slows down over a period of 3-12 months due to partial parasympathetic reinnervation, however, approximately 6-7% of patients remain severely symptomatic and require heart rate slowing agents. Other complaints such as decreased exercise capacity or effort dyspnea can occur in up to 14% of patients and they are usually attributed to faster than needed sinus rate at rest and during exercise.

Although in the vast majority of patients, the above mentioned symptoms are rather mild and do not decrease the patient's acceptance of CNA, in some may decrease the quality of life. Thus, a detailed assessment of the effects of CNA on exercise performance is clinically important. However, to date, no study addressed this issue.

There are several methods to assess exercise performance with cardiopulmonary exercise testing (CPET) being the most accurate and reference tool. It measures cardiorespiratory fitness and physiological responses to aerobic exercise in many conditions. CPET provides a comprehensive evaluation of the respiratory, circulatory, and metabolic responses to exercise that cannot be accurately measured by less precise methods such as standard exercise stress test. Therefore, we have chosen CPET to evaluate the effects of CNA on exercise performance in our patients.

Aim To assess one-year effects of CNA-induced total vagal denervation on cardiorespiratory fitness in patients undergoing CNA due to reflex asystolic syncope.