Towards Identification of Conductive Tissue in Pediatric Heart Surgery Using Fiber Optic Confocal Microscopy
Abhijit Mondal1, John Lackey2, Chao Huang2, Mossab Saeed1, Fei-Yi Wu1, Robert Hitchcock2, Frank Sachse2, *Aditya Kaza1
1Boston Children's Hospital, Boston, MA;2University of Utah, Salt Lake City, UT
OBJECTIVES: Damage to the cardiac conduction system during surgical repair of congenital heart defects constitutes a significant risk to pediatric patients as surgeons rely on anatomical landmarks for identifying the conduction system during surgery. We sought to determine specificity and sensitivity of fiber optic confocal microscopy (FCM) in identifying cardiac conductive tissue based on tissue microstructure in cardioplegia arrested ovine hearts in situ. We also evaluated the cardiotoxicity of fluorescein, a fluorescent marker of cardiac tissue microstructure.
METHODS: FCM imaging was conducted on arrested hearts of 1 to 6 month old sheep on cardiopulmonary bypass. A 1:1000 dilution of fluorescein was used for FCM imaging. The dye was delivered either topically (n = 8) or systemically via cardioplegia (n = 6). FCM imaging was performed on the sinoatrial node, atrioventricular node and working myocardium of the atrium and ventricle. FCM videos of 1-10 s duration were acquired during surgery and their location noted. Shorter 1-2 s video-clips were generated and randomly selected for evaluation by examiners blinded to the tissue type. Before evaluating, the examiners were given a 5-7 minutes training on the differences in nodal and working myocardium microstructures prepared using sample FCM images and video-clips.
Cardiotoxicity studies (n = 3) of fluorescein were also performed by comparing electrocardiogram (PR and QRS intervals) and ejection fraction at baseline and after topical application of fluorescein at 1:10, 1:100 and 1:1000 dilutions on the beating ovine heart.
RESULTS: A total of 162 randomly selected FCM video-clips of working myocardium (n = 81) and nodal tissue (n = 81) were separately evaluated by each blinded examiner (n =7). The blinded examiners classified each video-clip as nodal (sinoatrial or atrioventricular node tissue) or working myocardium based on tissue microstructure. The examiners achieved a high sensitivity and specificity of 93.7± 3.6% and 96.8 ± 3.9%, respectively. For all dilutions, application of fluorescein did not affect the normalized PR interval (p = 1), QRS interval (p = 1) and ejection fraction (p = 0.72) versus baseline.
CONCLUSIONS: FCM imaging enabled high sensitivity and specificity in distinguishing cardiac conductive tissue from working myocardium in the ovine model. Our study indicates that fluorescein is not cardiotoxic. We suggest that fluorescein-based FCM can serve as a safe and reliable intraoperative imaging modality towards reducing damage to cardiac conduction system in complex surgeries for repair of congenital heart defects in humans.
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