Automated Assessment of PVI Using a Novel EP Recording System

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.

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.

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.

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.

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.

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.

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.