Clinical trial NCT06038708: 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
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Syncope
Syncope, Vasovagal
Keywords: Syncope
Head-up Tilt Test
Closed Loop Stimulation
CLS
Lead sponsor: Biotronik SE & Co. KG
Sponsor class: INDUSTRY
First posted: 2023-09-15
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Heart Rate [Bpm] at Specific Time-points During Head-up Tilt Test (HUTT) Examination
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Systolic Blood Pressure at Specific Time-points During Head-up Tilt Test (HUTT) Examination
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Stroke Volume [ml] at Specific Time-points During Head-up Tilt Test (HUTT)
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Peripheral Resistance [Dyn·s/cm5] at Specific Time-points During Head-up Tilt Test (HUTT)
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Time of Maximum Spontaneous Heart Rate
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Time of Pacing Onset
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Time of Recovery of Spontaneous Rhythm After Pacing
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Time of Syncope
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Time of Tilt-down
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Duration of the Recovery Phase [Minutes]
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Slope in Heart Rate [Bpm/Minute] During the Recovery Phase
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
measure: Slope in Systolic Blood Pressure (mmHg Per Minute) During the Recovery Phase
timeFrame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Bolzano
country: Italy
facility: Ospedale di Bolzano - Azienda Sanitaria dell'Alto Adige
city: Napoli
country: Italy
facility: Monaldi - AORN dei Colli - Università della Campania "Luigi Vanvitelli"
Study officials:
References: