Automated Assessment of PVI Using a Novel EP Recording System

As part of the primary outcome, safety is also evaluated as the number of adverse events and device malfunctions reported by the study team at site, during the use of the CathVision Cube® System from the start of the procedure until discharge. The number of adverse events and device malfunctions is recorded in the site's source documents as well as in the case report form (CRF) and is duly informed to the Sponsor who also keeps the record.

Time frame: From EP procedure until study completion at discharge; an average of 24 hours.

Population: All enrolled subjects.

The primary outcome is to evaluate the sensitivity and specificity of the PVI Analyzer in the classification of the isolation status of veins, following the medical procedure known as pulmonary vein isolation (PVI). The information used for this has been obtained from the investigational CathVision Cube System. The PVI Analyzer determines whether the veins are isolated or not after pulmonary vein ablation. The proportion of correct negative (non-isolated) predictions among non-isolated vein data points and the proportion of correct positive (isolated) data points from isolated veins, provide the sensitivity and specificity data, respectively.

Time frame: From EP procedure until study completion at discharge; an average of 24 hours.

Population: The performance assessment was done in the PPT population, with a total of 85 subjects. Subjects undergoing PFA were excluded from this analysis despite being included in the PPT population, since the primary endpoint was specific to RF and Cryo procedures only.~Up to 248 EGMs were recorded at 'T-baseline' (prior to isolation) and labeled as ground-truth negative (non-isolated); and 250 EGMs were recorded at 'T-final' (after isolation) and labeled as ground-truth positive (isolated).

This secondary endpoint aimed to determine the sensitivity of the PVI Analyzer at the time of isolation, which requires the EGMs at the T PVI. The T PVI EGMs were extracted by taking EGM snippets of 4 seconds around the T PVI event. All of those EGMs were expected to be from isolated veins (ground-truth is isolated). Then, they were processed by the PVI Analyzer, and the last valid global isolation index output was used for endpoint assessment.

Time frame: From EP procedure until study completion at discharge; an average of 24 hours.

Population: In many cases, the actual isolation time was not directly observable, and the investigator was only asked to annotate T PVI if it was observed.~During RF procedures, T PVI can be difficult to observe and during cryo-balloon application, freeze noise from the cryoballoon can make identification of T PVI difficult. The annotation the EGMs at the T PVI was not always possible and only 116 valid EGMs at T PVI were collected. During processing, 17 EGMs were rejected by the PVI Analyzer.

The conventional EP system and CathVision Cube® System were running on two different PCs in the EP laboratory in parallel. The relevant EGM snippets were extracted from the conventional EP system using a time offset between the conventional EP system PC and the Cube PC. Since a very similar number of samples were used to compute the results, no statistical assessment of the sampling variation in the sensitivity and specificity was made. A paired McNemars test, with an alpha value of 0.05, was applied to analyze the differences in classification performance.

Time frame: From EP procedure until study completion at discharge; an average of 24 hours.

Population: It was not possible to extract all EGM snippets from the conventional systems, as all data from Toulouse was not available. Due to technical reasons and time constraints, only the first 12 patients from Ghent were included in the analysis.

The device's feasibility was evaluated by reassessing its accuracy. It refers to the consistency in the re-classification of pairs of non-overlapping samples throughout the different timepoints of ablation-prior to, during, and following the procedure. For this evaluation, the same EGMs of the primary endpoint were used, including only EGMs from T Baseline and T Final measurements from patients in sinus rhythm. The extraction of non-overlapping samples was selected by considering only those EGMs with a number of global isolation index values above 6. The global isolation index value is an indicator from the PVI analyzer that is used to assess the overall effectiveness of the ablation in isolating specific regions of the heart. The fourth and last global index returned by the PVI Analyzer were used as pairs for analyzing the outcome. The accuracy was calculated as the percentage of EGMs with agreement across timepoints with respect to the total number of EGMs performed.

Time frame: From EP procedure until study completion at discharge; an average of 24 hours.

Population: EGMs with a number of global isolation index values above 6 were selected. For those EGMs, the fourth and last global index returned by the PVI Analyzer were used. This value was compared at different time points of the procedure, to confirm whether there was an ECG agreement or not. The number of EGM with agreement was 475/495, and the number of EGM without agreement was 20/475.

The PVI isolation classification in non-sinus rhythm (NSR) from EP procedure was focused on the analysis of all EGM in non-sinus rhythm. The data analysis and processing were similar to those of the primary endpoint, but taking into consideration that subjects shall be in non-sinus rhythm during the duration of the EGM snippet. Apart from this, the processing was the same and the threshold was also defined as 50: values below 50 were classified as baseline, while values at or above 50 were considered as isolated veins.

Time frame: From EP procedure until study completion at discharge; an average of 24 hours.

Population: The performance assessment was done in the Per Protocol (PPT) population, with a total of 85 participants. The PVI isolation classification in non-sinus rhythm (NSR) from EP procedure was focused on the analysis of all EGM in non-sinus rhythm which in this case were 55 in T-baseline and 44 in T-final, a total of 99 ECGs. However, the system rejected 9 ECGs in T-baseline and 3 in T-final, therefore, the ECGs used for this secondary outcome were 46 in T-baseline and 41 in T-final.

This outcome assesses the overall classification of pulmonary vein isolation (PVI) in sinus rhythm (SR) based on the type of electrophysiology procedure performed. The classification provides insights into the accuracy of the procedure in achieving SR. The overall classification was evaluated in terms of sensitivity and specificity. To calculate specificity from the total number of EGMS analyzed, all the correct negatives (non-isolated) / Correct negatives + False positives were considered. To calculate sensitivity, all the correct positives (isolated) / Correct positives + False negatives were considered. As the sample size was not adjusted to detect the differences for variables other than the primary endpoint, the p-values obtained from the analyses of secondary outcomes should be viewed as complementary to the primary outcome results. Their primary purpose was to generate hypotheses rather than draw definitive conclusions.

Time frame: From EP procedure until study completion at discharge; an average of 24 hours.

Population: This secondary outcome assessed the overall classification accuracy of the PVI Analyzer in sinus rhythm (SR) computing the results only in radiofrequency and cryoballoon procedures. Therefore, the dataset used for the analysis is the same as for the primary endpoint (85), but subgrouping the data by the type of procedure.