Assessment of the Mechanism of Non-cardiac Syncope (2STEPS)

Assessment of the Mechanism of Non-cardiac Syncope by 24-hour Ambulatory Blood Pressure Monitoring (ABPM) and Tilt-table Short Cardiovascular Autonomic Function Battery (SCAFB)

Identifying the mechanism of non-cardiac syncope is the essential prerequisite for an effective personalized therapy.

Aim of this multicentre, prospective, cross-sectional, observational study is to assess effectiveness and diagnostic yield of a two-step standardized assessment which consists of 24-hour ambulatory blood pressure monitoring (ABPM) and of tilt-table Short Cardiovascular Autonomic Function Battery (SCAFB) which consists in carotid sinus massage (CSM), limited to patients ≥40-year-old, standing test, and head-up tilt test (HUT) performed one after the other in an uninterrupted sequence as a single procedure on a tilt table

Study Overview

• Status: Not yet recruiting
• Conditions: Syncope; Orthostatic Hypotension; Syncope, Vasovagal; Syncope, Carotid Sinus
• Intervention / Treatment: Diagnostic test: ABPM plys SCAFB

Detailed Description

Identifying the mechanism of non-cardiac syncope is the essential prerequisite for an effective personalized therapy. Indeed, the choice of appropriate therapy and its efficacy are largely determined by the mechanism of syncope rather than its aetiology or clinical presentation. The identified mechanism of syncope should be carefully assessed and assigned either to hypotensive or bradycardic phenotype, which will determine the choice of therapy (counteracting hypotension or counteracting bradycardia).

Several tests have been developed to identify the mechanism of non-cardiac syncope. The great number of tests, most of them being time-consuming, is one of the barriers for widespread utilization in the busy clinical practice. They are expensive and often not fully reimbursed by the health services.

Aim of this multicentre, prospective, cross-sectional, observational study is to assess effectiveness and diagnostic yield of a two-step standardized assessment which consists of 24-hour ambulatory blood pressure monitoring (ABPM) and of tilt-table Short Cardiovascular Autonomic Function Battery (SCAFB). SCAFB consists in carotid sinus massage (CSM), limited to patients ≥40-year-old, standing test, and head-up tilt test (HUT) performed one after the other in an uninterrupted sequence as a single procedure on a tilt table

The study hypothesis is that these two investigations, performed in sequence, can identify the mechanism of syncope in most of the patients in a quick and easy-to-perform way and at relatively low costs.

• Study Type: Observational
• Enrollment (Estimated): 275

Contacts and Locations

• Study Contact: Name: Michele Brignole, MD; Phone Number: +393204391422; Email: m.brignole@auxologico.it
• Study Contact Backup: Name: Antonella Groppelli; Email: a.groppelli@auxologico.it

Study Locations

• France
  • Marseille, France
    • University of marseille Aix en Provence
    • Contact: Jean Claude Deharo
• Italy
  • Florence, Italy
    • University of Florence
    • Contact: Andrea Ungar
    • Sub-Investigator: Andrea Ungar
  • Lavagna, Italy
    • ospdali del Tigullio
    • Contact: Roberto Maggi
  • Naples, Italy
    • Università della Campania Vamvitelli
    • Contact: Vincenzo Russo
  • MI
    • Milan, MI, Italy, 16149
      • IRCCS Istituto Auxologico Italiano
      • Contact: Michele Brignole; Phone Number: 3204391422; Email: mbrignole@outlook.it
      • Contact: Michele MB Brignole, MD; Phone Number: 3204391422; Email: mbrignole@outlook.it
      • Principal Investigator: Michele Brignole
• Netherlands
  • Amsterdam, Netherlands
    • AMC Universisty of Amsterdam
    • Contact: Frederik de Lange
• Spain
  • Barcelona, Spain
    • University of Barcelona Vall d'Ebron
    • Contact: Jaume Pascual
• Sweden
  • Stockholm, Sweden
    • Karolinska Institut
    • Contact: Artur Fedorowski

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with severe syncopes are those patients who are asking for mechanism-specific therapy because they are affected by recurrent syncopes impairing quality of life or have syncopes with absent or very short prodrome increasing the risk of injuries or are at risk of syncope during high-risk activities (e.g., driving, machine operation, flying, or competitive athletics, etc.).

Description

Inclusion Criteria:

• severe recurrent non-cardiac syncope referred for assessment of the mechanism of syncope. Non-cardiac syncope is diagnosed when the clinical features are consistent with reflex syncope and orthostatic hypotension, and cardiac syncope is ruled out .

Exclusion Criteria:

1. Non-syncopal causes of real or apparent loss of consciousness that may be incorrectly diagnosed as syncope (eg, unexplained falls, epilepsy, psychogenic pseudosyncope and other rare causes)
2. Established or suspected cardiac syncope in complying with the criteria of the European Society of Cardiology (ESC) syncope guidelines (1). Specifically, these were the patients with: (i) suspected cardiac arrhythmic syncope [inadequate sinus bradycardia (<50 b.p.m.) or sinoatrial block, second-degree Mobitz I atrioventricular block, second-degree Mobitz II or third-degree atrioventricular block, paroxysmal tachyarrhythmia or ventricular tachycardia, bundle branch block]; (ii) severe structural heart disease and/or significant ECG abnormalities, as defined in Table 2 of those guidelines (1).
3. Classical orthostatic hypotension diagnosed at the initial evaluation by Active Standing test
4. Constitutional or drug-induced persistent hypotension already diagnosed at the initial evaluation by office BP measurement or previous historical features
5. Non-severe forms of non-cardiac syncope, i.e., patients with rare and mild episodes occurring in low-risk situations. In these patients the investigation of the underlying mechanism of syncope is not necessary and treatment strategies are mainly based on education on preventive measures, lifestyle modification, and reassurance regarding the benign nature of the condition.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence	Prevalence of hypotensive and bradycardic phenotypes	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis	Case mix of etiologic diagnoses	1 month
Diagnostic yield	Diagnostic yield of ABPM and of SCAFB	1 month

Collaborators and Investigators

• Sponsor: Istituto Auxologico Italiano

Publications and helpful links

General Publications

• Rivasi G, Groppelli A, Brignole M, Soranna D, Zambon A, Bilo G, Pengo M, Sharad B, Hamrefors V, Rafanelli M, Testa GD, Rice C, Kenny RA, Sutton R, Ungar A, Fedorowski A, Parati G. Association between hypotension during 24 h ambulatory blood pressure monitoring and reflex syncope: the SynABPM 1 study. Eur Heart J. 2022 Oct 11;43(38):3765-3776. doi: 10.1093/eurheartj/ehac347.
• Brignole M, Rivasi G. New insights in diagnostics and therapies in syncope: a novel approach to non-cardiac syncope. Heart. 2021 Jun;107(11):864-873. doi: 10.1136/heartjnl-2020-318261. Epub 2021 Jan 18. Erratum In: Heart. 2021 Nov;107(22):e13.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: February 4, 2023
• First Submitted That Met QC Criteria: February 4, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Syncope; Orthostatic hypotension; Ambulatory blood pressure monitoring; Tilt table test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Autonomic Nervous System Diseases; Unconsciousness; Consciousness Disorders; Primary Dysautonomias; Orthostatic Intolerance; Hypotension; Syncope; Hypotension, Orthostatic; Syncope, Vasovagal
• Other Study ID Numbers: 09C337

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No