Non-invasive and invasive autonomic tests to facilitate cardioneuroablation and complex indications for transcutaneous lead extraction and discontinuation of permanent pacing

Funding Acknowledgements Type of funding sources: None. OnBehalf Rare-A-Care registry Background Extracardiac vagal nerve stimulation (ECANS) and cardioneuroablation (CNA) are promising methods to cure vagally mediated bradycardia and validate indications for permanent pacing for sinus node dysfunction (SND), atrioventricular blocks (AVB), tachycardia-bradycardia syndrome (TBS) and cardio-inhibitory or mixed reflex syncope (VVS). There are limited information on clinical utility of those procedures in validation of indication for continuation of permanent pacing (PM) and transcutaneous lead extraction (TLE). Methods Data were collected from prospective multicentre registry of CNA facilitated by interdisciplinary consultations, state-of-art autonomic tests, atropine/propranolol tests, electrophysiologic study as well as ECANS. Share-decision making were used by EP-HEART-TEAM to developed patient-oriented therapy. Results Between June 2018-Jan 2021 the first 102 consecutive patients underwent interdisciplinary approach before invasive EPS and/or invasive ECANS, to consider biatrial, binodal CNA, if possible to cure functional bradycardia. Eleven (10%) patients had implanted permanent PM"s due to SND/AVB/TBS/CI-VVS and were considered for TLE. In 2 out of 11 cases CNA was not performed due to: 1) structural advanced 2nd and 3rd degree AVB with indication for TLE and permanent HBP (no.1), 2) incidental severely symptomatic persistent 3rd degree AVB more than 15 year ago without any further bradycardia episodes (only TLE, no.2). In further 9 of 11 cases with PM CNA was performed, however TLE was not attempted in 2 patients [(SND + PVC ablation + indication for beta-blocker therapy due to IHD in older male. TLE had not yet been attempted to confirm long-term success therapy by patient and/or physician (no.3); two periprocedural successful CNA resulted in disappearance of CI reflex however despite pacing syncopal events persist due to mixed etiology (no.4)]. In further 7/11 cases TLE-s were performed. Three cases had TLE prior to CNA [VVS-CI + advanced functional AVB - prior 3 pacemaker reimplantations and further "rescue" CNA, (no.5); CI-VVS + pacemaker infection (no.6); TLE of PM + TBS no.7]. Finally, in 4 cases TLE was recommended after CNA [CI-VVS (no.8, no.9 and no.10); mixed etiology: TBS + VVS-CI + intermittent, recurrent pericardial efffusion due to lead perforation, PM syndrome, (no. 11)]. Conclusions Interdisciplinary and comprehensive autonomic approach with ECANS and CNA enable EP-HEART-TEAM to offer patient-oriented therapy with a complex clinical scenarios before final decision about TLE and discontinuation of permanent pacing therapy.

Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness

An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres.

Case 56: Autoimmune Small Fiber Neuropathy with Positive Ganglionic Acetylcholine Receptor Antibody

In this patient, autonomic tests were positive for small fiber neuropathy, mixed, length-dependent. Clinical workup was positive for ganglionic acetylcholine receptor antibody. Patient subsequently improved with immunotherapy with intravenous immunoglobulins.

Autonomic Tests

Autonomic tests are focused on the cardiovascular and sudomotor systems. Established cardiovascular reflex function tests are heart rate variability during paced deep breathing, Valsalva maneuver, and tilt test. Transcranial Doppler is essential to assess cerebral vasculature and blood flow regulation to orthostatic stress. Skin biopsy also assesses small sensory and sudomotor fibers. The test results can be graded by a quantitative scale for grading of cardiovascular reflex tests, transcranial Doppler, quantitative sudomotor axon reflex test, and small fiber (epidermal sensory and sweat gland) densities from skin biopsies (QASAT). The QASAT is the validated objective instrument for grading of dysautonomia, related small fiber neuropathy, and cerebral blood flow.

Autonomic Testing

Autonomic testing is an important addition to neurological evaluations. While there are many excellent textbooks on autonomic disorders, only a few texts focus on how to perform and interpret autonomic tests. This manual fills the gap, dealing mainly with the practical aspects of autonomic testing. In accord with the maxim that “a good picture is worth a thousand words,” signal drawings are heavily used throughout the text to explain and illuminate test results. This book has two parts. The first part describes in detail the Brigham protocol of autonomic tests, which includes cardiovascular tests (deep breathing, Valsalva maneuver, tilt tests), sudomotor assessment (quantitative sudomotor axonal reflex test and electrochemical skin conductance), and skin biopsies for assessment of epidermal and sweat gland small fibers. The cardiovascular tests use heart rate, blood pressure, respiratory parameters (respiratory rate and end tidal CO2), and cerebral blood flow velocity. All tests are graded with an updated quantitative scale for cardiovascular reflex tests and transcranial Doppler—the Quantitative Sudomotor Axon Reflex Test (QASAT)—and small fiber (epidermal sensory and sweat gland) densities from skin biopsies. The second part of the book describes 100 cases covering a variety of autonomic disorders. The cases are thematically grouped into orthostatic intolerance syndromes (neurally mediated syncope, orthostatic hypotension, postural tachycardia syndrome, inappropriate sinus tachycardia, orthostatic cerebral hypoperfusion syndrome, hypocapnic cerebral hypoperfusion, and pseudosyncope), dysautonomia in neurodegenerative disorders, small fiber neuropathies (idiopathic, secondary, inflammatory), and autonomic overactivity. The case descriptions are presented in a consistent format featuring pertinent clinical information, autonomic tests results, interpretation of testing, conclusions, and recommendations. This text is intended to be a guide for autonomic fellows, and for residents in neurology, general medicine, and other specialties, and for anyone who is interested in performing and interpreting autonomic tests.