Utilization of Confocal Microscopy During Cardiac Surgery

The investigators propose to translate confocal microscopy for use during open heart surgery. This tool will help discriminate between various types of tissues in the heart during surgery. One of the most feared complication after heart surgery is heart block. This flexible fiberoptic confocal microscope will help discriminate between the various types of tissues in the heart and thus help avoid injury to the conduction tissue during surgery.

Study Overview

• Status: Completed
• Conditions: Atrial Septal Defect
• Intervention / Treatment: Drug: Fluorescite; Device: Cellvizio 100 Series System with Confocal Miniprobes

Detailed Description

This is an interventional pilot study that proposes to evaluate the safety, logistical feasibility, and technological feasibility of using Fluorescite with fiberoptic confocal microscopy during cardiac surgery to discriminate between cardiac tissue and conduction tissue. During surgery to repair atrial septal defect, diluted Fluorescite will be added to the surface of the heart. The fiberoptic confocal microscope (Cellvizio 100 Series System with Confocal Miniprobe) will be used to record images in several different locations of the heart. The image files will be provided to blinded raters who will attempt to identify whether they contain cardiac tissue or conduction tissue. All subjects will be monitored while they are inpatient after surgery for any adverse events.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females between 30 days and 21 years old
• Undergoing elective surgery for closure of atrial septal defect
• Both parents attend pre-operative clinic appointment, to provide 2 parent consent, or an adult participant (age 18-21) may provide consent for him/herself

Exclusion Criteria:

• Prior history of adverse reaction to fluorescein sodium
• Prior history of renal failure or abnormal renal function
• Baseline PR interval > 220 msec or 98% for age
• Baseline HR > 87% for age
• Underlying genetic syndrome associated with progressive AV block of sinus node dysfunction (e.g. Holt-Oram or NKX2.5)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Imaging arm; Up to 5mL of 1:1000 dilute FLUORESCITE will be applied to cardiac tissue prior to imaging with Cellvizio 100 Series System with Confocal Miniprobes	Drug: Fluorescite; Dilute fluorescite will be applied to cardiac tissue prior to imaging; Other Names: fluorescein sodium; Device: Cellvizio 100 Series System with Confocal Miniprobes; Microscopy system will image cardiac tissue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Adverse Events Possibly Related to Study Intervention	All adverse events will be collected and relatedness to study intervention will be determined.	Surgery through discharge (approximately 5 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants For Whom FCM Imaging During Cardiac Surgery Was Feasible	Evaluated by measuring increased time on bypass, rate of enrollment, and the ability to incorporate this imaging modality into standard OR procedures. The additional time on bypass and ability to incorporate the imaging into standard OR procedures was assessed for each subject. 3 additional minutes on bypass was determined as reasonable per the protocol. The ability to incorporate the imaging was considered successful when it did not interfere with the planned clinical procedure. The rate of enrollment was evaluated for the study as a whole.	Surgery through discharge (approximately 5 days)
Percentage of Agreement in Classification of FCM Images	A first reviewer selected 60 FCM images and classified them as reticulated, striated, or of poor quality (indistinguishable microstructure) with 20 images in each group. Quality of the files is measured by the ability of 8 blinded reviewers to classify the images accurately.	After all participants completed the study (range 2 months to 1 year post surgery)

Collaborators and Investigators

• Sponsor: Aditya Kaza
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Aditya K Kaza, Boston Children's Hospital

Publications and helpful links

General Publications

• Kaza AK, Mondal A, Piekarski B, Sachse FB, Hitchcock R. Intraoperative localization of cardiac conduction tissue regions using real-time fibre-optic confocal microscopy: first in human trial. Eur J Cardiothorac Surg. 2020 Aug 1;58(2):261-268. doi: 10.1093/ejcts/ezaa040.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 2, 2018
• Primary Completion (ACTUAL): March 4, 2019
• Study Completion (ACTUAL): April 26, 2019

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: June 14, 2017
• First Posted (ACTUAL): June 16, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 3, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects; Heart Septal Defects, Atrial
• Other Study ID Numbers: P00013570; R56HL128813 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes