Clinical trial NCT03636100: Release of Acetylcholine From the Ganglionated Plexus During the Thaw Phase of Cryoballon Pulmonary Vein Ablation (GP RESPONSE Study)
Official title: Systemic Release of Acetylcholine From the Autonomic Ganglionated Plexus: a Proposed Mechanism of Induced Hypotension During the Thaw Phase of Cryoballon Pulmonary Vein Ablation (GP RESPONSE Study)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Atrial Fibrillation
Keywords: Atrial fibrillation
Catheter ablation
Cryoballon ablation
Acetylcholine
Ganglionated plexus
Pulmonary veins
Pulmonary vein isolation
Lead sponsor: Saint Luke's Health System
Sponsor class: OTHER
First posted: 2018-08-17
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A total of 14 patients age 18-80 with atrial fibrillation undergoing first time cryoballoon ablation will be enrolled.

Brief summary: Determine whether the presence of acetylcholine in the systemic circulation, correlates with the hypotensive response observed during the thaw phase of cryoballoon ablation.

Detailed description: This will be a two-phase (feasibility and primary study phases), prospective observational study with pulmonary vein ablation applications during which a hypotensive response is not observed serving as within-subject controls. A total of 14 patients age 18-80 with atrial fibrillation undergoing first time cryoballoon ablation will be enrolled. Exclusion criteria are any prior left atrial ablation or cardiac surgery, a hemoglobin level of \< 12.0 g/dL, or refusal or inability to provide informed consent.

The ablation procedure will be carried out per routine clinical practice by one operator. Two cryoballoon applications targeting 180 seconds per application will be performed per vein. Applications may be abbreviated at the discretion of the operator for indications such as balloon temperatures reaching the mid -50s C, esophageal temperatures approaching 20 C, or a decrease in diaphragmatic movement during phrenic nerve pacing. Application times may be extended to 200 to 240 seconds, also at the discretion of the operator, if within-freeze target temperatures (such as -30 C by 30 seconds or -40 C by 60 seconds) are not met.

A hypotensive response will be defined as a transient ≥ 20% decrease in systolic blood pressure from baseline (start of thaw) during the thaw phase and up to 60 seconds post-end of thaw (balloon deflation). A partial hypotensive response will be defined as a transient 10-19% decrease in systolic blood pressure. For all patients, the time from the end of the cryoballoon freeze to the end of the thaw, to the onset of the hypotensive response, and to blood pressure recovery within 10% of baseline will be recorded. Blood pressure and heart rate will be recorded at each time point. For the first 4 patients (phase I), blood samples of 2-3mL each will be drawn from the mid-right atrium at baseline and then at 30, 60 and 90 seconds after the end of each cryoballoon freeze application. Samples will also be drawn at onset of hypotension and 30 seconds later (superseding the drawing of other samples in the first 90 seconds post-end of freeze), and at blood pressure recovery. Samples will be drawn within 10 seconds of each specified time point; or will not be obtained and will be marked as a missing data point. If more than 20% of the specified data are missing for a given subject, that subject will be excluded from analysis. The samples will then be run on a commercially available 96-well colorimetric assay kit by Cell Biolabs Inc (catalog number STA-603) to assay for acetylcholine.

If the first phase of the study demonstrates the presence of acetylcholine at one or more time points during the thaw phase of 20% or more of cryoballoon applications during which a hypotensive response is observed, the study will proceed to phase 2. The results will be used to determine the optimal time point(s) at which to obtain samples during the second phase of the study (remaining 10 patients), with an anticipated need for 2-4 samples per cryoballoon application, one at start of thaw, another at a determined time point, and when there is a hypotensive response at the onset of hypotension and at blood pressure recovery. An interim report will be produced detailing the observations of phase 1 and specifying the plan for obtaining samples in phase 2.

Eligibility criteria: Inclusion Criteria:

* patients with atrial fibrillation undergoing first time cryoballoon ablation
* age 18-80

Exclusion Criteria:

* any prior left atrial ablation or cardiac surgery
* hemoglobin level of \<12.0 g/dL
* refusal or inability to provide informed consent

Primary outcomes:
measure: Individual acetylcholine levels
timeFrame: 1 day
Secondary outcomes:
measure: Group acetylcholine levels
timeFrame: 1 day
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Saint Luke's Mid America Heart Institute
state: Missouri
Study officials:
References:
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