Intraoperative localization of cardiac conduction tissue regions using real-time fibre-optic confocal microscopy: first in human trial

Abstract

Objectives: The aim of this study was to evaluate the feasibility and safety of fibre-optic confocal microscopy (FCM) using fluorescein sodium dye for the intraoperative location of conduction tissue regions during paediatric heart surgery.

Methods: The pilot study included 6 patients undergoing elective surgery for the closure of isolated secundum atrial septal defect aged 30 days to 21 years. FCM imaging was integrated within the normal intraoperative protocol for atrial septal defect repair. Fluorescein sodium dye was applied on the arrested heart. FCM images were acquired at the atrioventricular node region, sinus node region and right ventricle (RV). Total imaging time was limited to 3 min. Any adverse events related to the study were recorded and analysed. Subjects received standard postoperative care. Trained reviewers (n = 9) classified, de-identified and randomized FCM images (n = 60) recorded from the patients as presenting striated, reticulated or indistinguishable microstructures. The reliability of reviewer agreement was assessed using Fleiss' kappa.

Results: The FCM imaging instruments were integrated effectively into the cardiac surgery operating room. All adverse events found in the study were deemed expected and not related to FCM imaging. Reticulated myocardial microstructures were found during FCM imaging at atrioventricular node and sinus node regions, while striated microstructures were observed in RV. Reliability of agreement of reviewers classifying the FCM images was high (Fleiss' kappa: 0.822).

Conclusions: FCM using fluorescein sodium dye was found to be safe for use during paediatric heart surgery. The study demonstrates the potential for FCM to be effective in identifying conduction tissue regions during congenital heart surgery.

Clinical trial registration number: NCT03189134.

Keywords: Conduction tissue; Congenital heart surgery; Intraoperative confocal imaging; Pilot study; Tissue microstructure.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Figures

Figure 1:

FCM system and operating room schematic. (A–C) Components of the FCM system. (A) The movable tower consisting of the display on top with a keyboard and remote footswitch for operating the microscope. Beneath the display and keyboard are the laser scanning unit and processing computer. The footswitch is stored in the lowest shelf on the tower. (B) A GastroFlex UHD miniprobe is ∼3-m long with a connector on the proximal end that attaches to the laser scanning unit. (C) The distal end of probe consists of a small objective, which is manoeuvred for imaging. (D) Schematic representation of the cardiac operating room showing the position of the FCM movable tower and the routeing of the miniprobe to the surgeon. FCM: fibre-optic confocal microscopy.

Figure 2:

Fibre-optic confocal microscopy images from paediatric patient. Striated microstructures captured during imaging working myocardium while approaching the (A) sinus node and (D) atrioventricular node regions. Reticulated tissue microstructures captured during imaging in the (B and C) sinus node region and (E and F) atrioventricular node region (scale bar: 20 μm).