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Disclosure Information Brian W. McCrindle

Disclosure Information Brian W. McCrindle. I have the following financial relationships to disclose: Consultant /investigator for: Aegerion Daichii Sankyo Janssen Merck I will not discuss off label use and/or investigational use in my presentation.

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Disclosure Information Brian W. McCrindle

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  1. Disclosure InformationBrian W. McCrindle I have the following financial relationships to disclose: Consultant /investigator for: Aegerion Daichii Sankyo Janssen Merck I will not discuss off label use and/or investigational use in my presentation.

  2. CHSS Work Weekend – November 18-20, 2016 A Modest Proposal: We are Overdue for an International Fontan Registry Brian W. McCrindle, MD MPH Labatt Family Heart Centre, The Hospital for Sick Children Department of Pediatrics, University of Toronto

  3. A Modest Proposal Jonathan Swift - 1729

  4. Saturn Devouring His SonFrancisco Goya - 1823

  5. An Uncertain RealityDonald Trump - 2016

  6. The Fontan ProcedurePromise and Reality

  7. Single ventricle palliation Natural history: - rare long-term adult survivors, balanced circulations Early palliations: - arterial shunts, ductal stent, SVC connections - pulmonic outflow procedures, pulmonary banding - systemic outflow procedures, DKS - atrial septostomy - Norwood, hybrid procedures

  8. Pulmonary Atresiawith Intact Ventricular Septum

  9. Single ventricle palliation Tricuspid atresia (Wilder et al. JTCVS 2015): 6 year survival: arterial shunt 85%, PA band 93%, SCPC 93% Systemic right venticle (Ohye et al. NEJM 2011): 12 month survival: Norwood RVPA 74%, MBT 64% Norwood interstage mortality 12% (Ghanayem et al, JTCVS 2012) Outcomes after SCPC (Alsoufi et al. EJCTS 2012): 6 year competing risks: 17% dead, 76% Fontan, 7% still waiting

  10. Single ventricle palliation Cavopulmonary connections: 1958 Glenn – SVC to distal RPA shunt 1971 Fontan/Baudet – “Fontan” procedure 1971-73 Bjork, Kreutzer – modifications 1972 Azzolina – bidirectional SVC anastomosis 1988 DeLeval – lateral tunnel 1989 Norwood/Jacobs – hemi-Fontan 1990 Marcelletti – extracardiac conduit

  11. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10 n=1,052 patients with Fontan from 1973-2012 Type of Fontan operation Atriopulmonary connection 59% Lateral tunnel 25% Extracardiac conduit 11% Other 5%

  12. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10 n=1,052 patients with Fontan from 1973-2012 Pre-operative anatomy Tricuspid atresia 26% Double inlet LV 26% Heterotaxy 13% Pulmonary atresia/ IVS 3% HLHS 2% Other 30%

  13. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10 Overall survival 71% 61% 43%

  14. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10 Causes of death known for 281 of 426 patients Primary cardiac cause 83% (4 malignancies) Contributing factors Respiratory failure 36% Renal insufficiency 30% Sudden death/arrhythmia 19% Bleeding complications 18% DIC / sepsis 17% PLE 11% Hepatic insufficiency 10%

  15. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10

  16. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10 Overall survival by surgical era 2001+ 1991-2000 < 1990

  17. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10 Overall survival by Fontan type Extracardiac conduit Other Lateral tunnel AP connection

  18. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10 Overall survival by lesion

  19. 40 year follow-up after the Fontan operation: Long-term outcomes of 1,052 patients.Pundiet al. JACC 2015; 66:1700-10

  20. Trends in Fontan surgery and risk factors for early adverse outcomes: ANZFontan Registry.Iyengar et al. JTCVS 2014; 148:566-75 Australia and New Zealand Fontan Registry 1975-2010 n=1095 Fontans, 1071 with sufficient data 1989 previous palliations in 990 patients

  21. Trends in Fontan surgery and risk factors for early adverse outcomes: ANZFontan Registry.Iyengar et al. JTCVS 2014; 148:566-75 Early outcomes by era 1975-90 1991-2000 2001-10 Early mortality 8% 4% 1% Early failure 9% 7% 4% Prolonged effusions 4% 8% 8% LOS >30 days 16% 12% 10% Composite outcomes 26% 20% 12% * Similar breakdown by Fontan type (AP > LT > ECC) Outcomes associated with AP connection type, age at Fontan, underlying morphology (HLHS, heterotaxy), high PA pressures

  22. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38 Follow-up of 1006 survivors of 1089 patients

  23. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38 Overall survival by Fontan type Extracardiac conduit Lateral tunnel AP connection

  24. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38

  25. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38 Freedom from late Fontan failure Non-HLHS RV LV HLHS NYHA III/IV, PLE/plastic bronchitis, Fontan conversion or takedown, transplantation, death

  26. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38

  27. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38 Freedom from late adverse events Failure, SVT, stroke, pulmonary embolism, pacemaker

  28. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38

  29. Redefining expectations of long-term survival after the Fontan procedure: ANZFontan Registry. D’Udekem et al. Circulation 2014; 130:S32-S38 Freedom from supraventricular tachycardia Extracardiac conduit Lateral tunnel AP connection

  30. NIH Pediatric Heart NetworkFontan Cross-sectional Study Initial PI – BJ Clark (Anderson, Atz) 7 clinical centres; data collection 2003-2004 Inclusion: 6-18 years of age Minimum participation: echo, BNP, parent CHQ Followed at study centre (or affiliate) Exclusion: Important disorder precluding participation

  31. NIH Pediatric Heart NetworkFontan Cross-sectional Study

  32. NIH Pediatric Heart NetworkFontan Cross-sectional Study Limitations: Undefined denominator; not an inception cohort Incomplete participation; representativeness and generalizability Fewer Hispanics Fewer with dev. delay / learning disability Retrospective collection of medical history

  33. NIH Pediatric Heart NetworkFontan Cross-sectional Study Contemporary outcomes after the Fontan procedure: a Pediatric Heart Network Study. Anderson et al. J Am Coll Cardiol 2008; 52:85. Main findings: • FHS within normal range for 80% • BNP low (median 13 pg/mL) • Ejection fraction normal for 73% • Evidence of diastolic dysfunction in 72% • Peak VO2 66% of normal (many sub-max) • Lower EF, more AVVR in single RV’s

  34. NIH Pediatric Heart NetworkFontan Cross-sectional Study Relationships of patient and medical characteristics to health status in children and adolescents after the Fontan procedure. McCrindle et al. Circulation 2006; 113:1123.

  35. NIH Pediatric Heart NetworkFontan Cross-sectional Study

  36. NIH Pediatric Heart NetworkFontan Cross-sectional Study

  37. NIH Pediatric Heart NetworkFontan Cross-sectional Study

  38. NIH Pediatric Heart NetworkFontan Cross-sectional Study

  39. NIH Pediatric Heart NetworkFontan Cross-sectional Study

  40. NIH Pediatric Heart NetworkFontan Cross-sectional Study Laboratory measures of exercise capacity and ventricular characteristics and function are weakly associated with functional health status after Fontan procedure. McCrindle et al. Circulation 2010; 121:34. Overall, more associations with physical FHS than psychosocial FHS; weak associations in general. • Higher BNP, but R2=0.01. • Physical FHS and exercise (max work rate; R2=0.09), echo (Tei index [interaction], end-systolic volume, AVVR; R2=0.14), MRI (mass/EDV, ESV; R2=0.11)

  41. NIH Pediatric Heart NetworkFontan Cross-sectional Study Clinical perspective: 1. The impact of treatment strategies targeted toward those with important laboratory abnormalities in the pathological range may influence FHS to an unknown degree but should be an important component of future studies. 2. Strategies targeting FHS and its non-cardiac determinants directly, such as through rehabilitation programs and by addressing psychosocial morbidities, may have a greater impact on health-related quality of life. 3. Such programs should be developed and evaluated for these high-risk and complex patients.

  42. NIH Pediatric Heart NetworkFontan Cross-sectional Study Longitudinal assessment: Fontan 2 Follow-up of current cohort Vital status, FHS, interim medical events, access to health care, and self-reported availability and willingness to participate in future studies Fontan 3 (SVR 2 and 3) Further follow-up of current cohort Includes cardiopulmonary exercise testing, echo, ECG, BNP, biorepository Transition and access to adult heart care

  43. The long-term management of children and adults with a Fontan circulation: A systematic review.Gnanappaet al. PediatrCardiol 2016 [Epub] Systematic review using PRISMA guidelines: • Reasonable quality evidence for non-inferiority of ASA over warfarin for thromboprophylaxis in standard risk Fontans • No strong evidence for routine use of ACE inhibitors, beta blockers, pulmonary vasodilators • Little evidence for arrhythmia treatment, exercise restriction/prescription, routine fenestration closure, elective Fontan conversion, screening/management of liver abnormalities Survey of cardiologists (ANZ – 50% response): no uniformity

  44. Pulmonary Atresiawith Intact Ventricular Septum

  45. No simple answers Pre-Fontan optimization Preservation of optimal ventricular function Preservation of low pulmonary vascular resistance (systemic vascular resistance, vascular function, inflammation) Systemic venous / lymphatic hypertension Hepatic cirrhosis, PLE, plastic bronchitis Thrombosis, arrhythmia, renal dysfunction, sarcopenia, osteoporosis, lymphopenia Neurodevelopmental / psychosocial / functional outcomes / poor growth (short stature) / pregnancy

  46. Need for data Uniform (and deep) institutional data collection Single ventricle survivorship programs

  47. The relentless effects of the Fontan. Rychik. SeminThorac CV Surg 19:37-43

  48. Why doesn’t everyone do this? • We don’t/can’t measure some of these things. • It’s way too complicated / expensive / resource-intensive. • My patients won’t do it. • My patient has unique features. • I followed it and didn’t believe (ie. agree with) the results, or didn’t use it, or didn’t know what to do. • Our results are better with …. • Our results are better than ….

  49. The traditional approach to risk stratification and prediction Relationships between factors and outcomes: Causal Confounder Mediators Effect modifiers / interaction Random error Based on probability theory – aimed at confidence Univariable to multivariable approach

  50. The traditional approach to risk stratification and prediction More complex stats to address more complex questions – yields more complex answers, shades of grey or “it depends”. • Longitudinal models • Multiple phases of risk • Competing outcomes • Repeating and interim events • Time-varying covariates Nonetheless, the overall R2 remains low.

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