Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial (BIO|Sync-HUTT)

BIO|Sync-HUTT: Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial

The purpose of this study is to explore changes in patients' hemodynamic parameters during the Head-Up Tilt Test ("HUTT") and their timing with respect to onset of the Closed Loop Stimulation (CLS) pacing. This study aims to add knowledge to better understand the mechanisms underlying recurrent syncopal events and optimal pacing programming.

Study Overview

• Status: Completed
• Conditions: Syncope; Syncope, Vasovagal

Detailed Description

The 2021 European Society of Cardiology guidelines recommend cardiac pacing in patients aged >40 years with tilt-induced asystolic reflex syncope (class I, level of evidence A). The recommendation relies on recent results from the multicentre, randomised, double-blinded, parallel-design BIOSync trial (NCT02324920). The BIOSync study provided evidence of benefit of dual chamber pacing in patients with tilt-induced reflex syncope and confirmed the role of Head-up Tilt Table (HUTT) test as a diagnostic method for cardiac pacing in reflex syncope. The Closed Loop Stimulation (CLS) is able to measure changes in intracardiac impedance during the systolic phase of each cardiac cycle which are strictly correlated to the increased heart rate and right ventricular contraction speed which are usually present during the pre-syncope phase of the reflex. It was hypothesized that an early onset of CLS pacing may be triggered by the compensatory increase in heart rate to counteract vasodilation and pressure drop during the pre-syncope phase of the reflex. The BIOSync study showed a 77% reduced risk of syncope in the DDD-CLS group as compared to pacing off. The design of the BIOSync study did not allow to assess the specific effect that CLS adds to dual-chamber pacing. Despite DDD-CLS pacing, 22% of patients had syncopal recurrence in 2 years. Further investigations are therefore needed in order to reduce this failure rate. Indeed, it is still unclear whether syncopal recurrences should be ascribed to dominant vasodilation or if the CLS programming/functioning needs optimization to more adequately sustain cardiac output during reflex in these specific cases.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Italy
  • Bolzano, Italy, 39100
    • Ospedale di Bolzano - Azienda Sanitaria dell'Alto Adige
  • Napoli, Italy, 80131
    • Monaldi - AORN dei Colli - Università della Campania "Luigi Vanvitelli"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with reflex syncope and positive cardioinhibitory response to Head-Up Tilt Test (HUTT) who had already participated in the BIOSync study.

Description

Inclusion criteria

• Ability to understand the nature of the study.
• Willingness to provide written informed consent.
• Patients undergoing HUTT for monitoring of syncope, therapy adjustment, training or other medical reasons during ordinary follow-up, irrespective of study participation
• Patients who participated in the BIOSync study*.
• Patients with a dual-chamber pacing system equipped with the CLS algorithm. * If needed, inclusion of other patients who did not participate in the BIOSync study will be considered to complete study cohort, provided that they have already a CLS pacemaker system and fulfill the same inclusion/exclusion criteria of the BIOSync study.

Exclusion criteria

• Pregnant or breast feeding women.
• Age less than 40 years.

• Patients who after the BIOSync study participation have developed the following:

  • Any indication to pacemaker different from reflex syncope with positive HUTT response; or
  • Any classified indication to implantable defibrillator, cardiac resynchronization therapy according to current guidelines; or
  • Any cardiac dysfunctions likely leading to loss of consciousness (overt heart failure, ejection fraction <40%, myocardial infarction, diagnosis of hypertrophic or dilated cardiomyopathy, clinically significant valvular disease, sinus bradycardia <50 bpm or sinoatrial block, Mobitz I second degree atrioventricular block, Mobitz II second or third degree atrioventricular block, complete bundle-branch block).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate [bpm] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down	Instantaneous measurement of heart rate value at specific time-points during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Systolic and diastolic blood pressure [mmHg] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down	Instantaneous measurement of blood pressure at specific time-points during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Stroke volume [ml] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down	Instantaneous measurement of stroke volume at specific time-points during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Peripheral resistance [dyn·s/cm5] at time of maximum spontaneous heart rate, at time of pacing onset, at time of recovery of spontaneous rhythm after pacing, at time of syncope, at time of time of tilt-down	Instantaneous measurement of peripheral resistance at specific time-points during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of maximum spontaneous heart rate [s]	Recording of a specific time-point during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of pacing onset [s]	Recording of a specific time-point during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of recovery of spontaneous rhythm after pacing [s]	Recording of a specific time-point during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of syncope [s]	Recording of a specific time-point during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of tilt-down [s]	Recording of a specific time-point during HUTT examination	From the start to the end of the HUTT examination, assessed up to 45 minutes
Duration of the recovery phase [s]	Interval from maximum pacing rate to basic rate or spontaneous rhythm	From the start to the end of the HUTT examination, assessed up to 45 minutes
Slope in heart rate [bpm per sec] during the recovery phase	Calculation of the rate of change of heart rate from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery	From the start to the end of the HUTT examination, assessed up to 45 minutes
Slope in systolic blood pressure (mmHg per sec) during the recovery phase	Calculation of the rate of change of systolic blood pressure from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery	From the start to the end of the HUTT examination, assessed up to 45 minutes

Collaborators and Investigators

• Sponsor: Biotronik SE & Co. KG

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2022
• Primary Completion (Actual): May 12, 2023
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Syncope; Closed Loop Stimulation; CLS; Head-up Tilt Test
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Autonomic Nervous System Diseases; Unconsciousness; Consciousness Disorders; Primary Dysautonomias; Orthostatic Intolerance; Syncope; Syncope, Vasovagal
• Other Study ID Numbers: BA117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared on request to the corresponding author with permission of BIOTRONIK SE & Co. KG.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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