Insert any picture or image you like here AAOCA: Predictors of Ischemia Study Design CHSS Work Weekend November 18-20th Julie Brothers, M.D. Medical Director, Coronary Anomaly Management Program The Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania Marshall Jacobs, M.D. Director of Pediatric Cardiac Surgery Outcomes Research Johns Hopkins School of Medicine Insert any picture or image you like here

CURRENT REGISTRY STATUS

Participating Centers 39 Member Institutions

AAOCA Cumulative Enrollment & Number of Participating Institutions We now have 39 institution that are enrolling into AAOCA. Do you want me to take out the red line for the enrolling institutions? Enrollment numbers for 2016 are as of October 11, 2016,

Patient Characteristics N (percent of current enrollment) Current Enrollment 541 Alive 529 (97.8%) Average age at diagnosis 10.3 +/- 6 years Male gender 358 (66%) Prospectively enrolled 419 (77.4%) Surgical 300 (55.4%) As of Nov 10 2016 current numbers 541 enrolled 529 alive 12 dead One new deceased pt 9 years old elective repair LMCA went on ecmo 13 aborted sudden death Males 358 66.1% females 183 Prospective 419 77.4% Retrospective 122 surgery Yes 300 55.4% No 241

Hypothesis/Goal There will be differences in morphologic characteristics in patients with AAOCA who experience SCA or present with other evidence of myocardial ischemia Sub-cohort analysis of patients who have had well-documented episodes of myocardial ischemia or significant arrhythmia Goal to risk stratify patients based on a combination of clinical history and details of coronary morphology

Working Definition of Ischemia Sudden cardiac arrest or death Documented complex ventricular arrhythmia Exercise test J-point depression at least 2 mm or ST segment depression > 1 mm with flat/downsloping ST segment at 60 msec Increasing ventricular arrhythmias with exercise Lack of BP response Imaging Stress echo or nuclear scan with WMA or perfusion defect in correct coronary distribution territory

Summary of Ischemic Patients Description Number Documented Ischemia 29 Coronary Anatomy AAORCA 14 AAOLCA Both 1 Male Gender 25 Surgical Patients 24 Aborted Sudden Death 12 4 8 (one from non-coronary sinus) I don’t have numbers yet Julie but I know we have many more “true” ischemic patients enrolled. A few more aborted sudden death patients one new dead who died after OR. I just screened one patient who’s father was Dx at age 35 with MI and had surgery, this patient also had surgery. Not sure if I can get any information on the fathers anomaly, Definition of “ischemia”: 1 or more positive ischemia tests (among 210 patients tested) or presentation consistent with ischemia or lethal arrhythmia

Aborted Sudden Death Patients Status Coronary anomalous Symptoms Age at Diagnosis (yrs) Age at time of Death (yrs) Gender Aborted SCD, died post-operatively on ECMO AAOLCA Arrythmia, MI, ECMO. To OR for unroofing 1 6 F Aborted SCD, died in CCU CPR V-fib AED x2 14 M Alive post witness arrest Arrest post cross country run, CPR and AED 12 N/A AAOLCA (from non-coronary sinus) V-Fib with exercse, AED CPR x1min 16 Arrest with basketball, Vfib arrest, Defib x 2 CPR, AED for V fib 13 Arrest CPR 10 Alive s/p witnessed arrest AAORCA CPR AED applied and cardioverted 18  N/A arrest post cross country run, CPR and AED syncope in car, CPR briefly 11 Arrest playing basketball, AED   Median age at diagnosis 13.8

210 patients underwent ischemia testing, 181 negative Among 181 non-ischemic patients, 76% had AAORCA Among 29 ischemic patients, AAORCA = AAOLCA Variables other than just anomalous coronary laterality are predictors of ischemia These appear to be more prevalent with AAOLCA than AAORCA

ICL ECHO Review n=58 29 Ischemic patients 29 Non-Ischemic patients Age Matched 29 Non-Ischemic patients 20 studies previously reviewed 38 to be reviewed Made this slide up not sure if its helpful or not. Shubhika Craig and Luc Reviewer 1 =17 Reviewer 2 =18 Reviewer 3 =19 8 studies reviewed by all 3

Ischemic Group Studies Available N=58 Total N= patient CT study report in Database MRI study report in Database # of CT-CD's available # of MRI-CD's available N=Patients with Both studies done N= Patients with Both have CD's for review Ischemic group 29 14 8 6 4 Non-Ischemic group 19 11 3 2 1 Total 58 33 12 25 9

Image Review: Echo Among 201 echos received for patients with ischemic testing, 87 have had core lab (ICL) review and 114 have not been reviewed *=died without echo ICL Review No ICL Review Unavailable * Ischemic Patients 8 20 1 Non-Ischemic 79 94 Total 87 114

CT/MRI 121 have other imaging modalities NOT reviewed Issues with limited data sets sent to the CHSS DC for reading CTA/MRI

Questions/Issues Do we want to/need to review all of the echos in the cohort? Are the CT/MRI data necessary (I say yes) Should we attempt to get the full dataset from each institution? Is there anything else we should be considering?

Acknowledgments Thank you very much The CHSS members and CHSS Data Center Susan McIntyre, Clinical Research Nurse Coordinator, Data Center All of the participating AAOCA patients and their families The Registry has been generously funded by: Michael H. Ludwig Memorial Foundation Anthony’s Heroes for Hearts Children’s Heart Foundation Cardiac Center at the Children’s Hospital of Philadelphia Children’s Mercy Hospital, Kansas City Cardiovascular and Critical Care Research Center, Children’s Hospitals and Clinics of Minnesota Cardiac Surgery Research and Teaching Fund, Hospital for Sick Children, Toronto