1. Dallas 2015 TFQO: Vinay Nadkarni MD COI#249 EVREV 1: Graeme Maclaren MBBS COI#98 EVREV 2: Ravi Thiagarajan MBBS, MPH COI#149 Taskforce: PALS Peds 819 : Pre-arrest Care of Pediatric Dilated Cardiomyopathy or Myocarditis

2. Dallas 2015 COI Disclosure (SPECIFIC to this systematic review) Graeme Maclaren COI#98 Commercial/industry None Potential intellectual conflicts Chairman, Asia-Pacific Chapter, ELSO Ravi Thiagarajan COI#149 Commercial/industry Bristol Myers Squibb (Events adjudication committee) Potential intellectual conflicts ELSO registry Co-Chair

3. Dallas 2015 2010 Treatment Recommendation “Topic not reviewed in 2010”.

4. Dallas 2015 C2015 PICO Population: Pediatric patients with dilated Cardiomyopathy (DCM) or Myocarditis in a pre-arrest state Intervention: Any Pre-Arrest management Comparison: Standard care/No treatment Outcomes: 9-Critical Survival with Favorable neurological/ functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year 7-CriticalSurvival to hospital discharge 5-ImportantCardiac arrest frequency 5-ImportantROSC

5. Dallas 2015 Inclusion/Exclusion & Articles Found Inclusions: Dilated Cardiomyopathy, Myocarditis, Children, shock, pre-arrest, cardiac arrest, pre- arrest treatment. We searched for RCTs and observational studies. We excluded studies with only post-arrest management Number of Articles Search Identified: 548 articles Initial review: 67 article (2 RCTs; 65 Non-RCTs); Excluded: 481 Final Inclusion: 5 articles (All Non-RCTs; 1 not identified from initial search); Excluded 62

6. Dallas 2015 Included Articles Lynch, Johanne; Pehora, Carolyne; Holtby, Helen; Schwarz, Steven M; Taylor, Katherine;Cardiac arrest upon induction of anesthesia in children with cardiomyopathy: an analysis of incidence and risk factors. Paediatr Anaesth Sep 2011; 21 (9): 951-7. Song, M.-K.;Baek, J.-S.;Kwon, B.-S.;Kim, G.-B.;Bae, E.-J.;Noh, C.-I.;Choi, J.-Y. Clinical spectrum and prognostic factors of pediatric ventricular tachycardia. : Circ. J. 2010; 74 (9): 1951-1958 Eicken, Andreas; Kolb, Christof; Lange, Sylvia; Brodherr-Heberlein, Silke; Zrenner, Bernhard; Schreiber, Christian; Hess, John. Implantable cardioverter defibrillator (ICD) in children. Int. J. Cardiol. Feb-8-2006; 107 (1): 30-5. Greissman, A.;Silver, P.;Nimkoff, L.;Sagy, M.. Transvenous right ventricular pacing during cardiopulmonary resuscitation of pediatric patients with acute cardiomyopathy. PEDIATR. EMERG. CARE 1995; 11 (1): 17-24. Teele SA, Allan CK, Laussen PC, Newburger JW, Gauvreau K, Thiagarajan RR. Management and Outcomes in Pediatric Patients Presenting with Acute Fulminant Myocarditis. J Pediatr. 2011 Apr;158(4):638-643

7. Dallas 2015 2015 Proposed Treatment Recommendations We suggest Implantable Cardiac Defibrillator (ICD) and Anti-arrhythmic medications for pre-arrest management of cardiac arrest in pediatric dilated cardiomyopathy or myocarditis (weak recommendation, very low quality evidence) We suggest use of ECMO for patients with myocarditis presenting with dysrhythmia, lactic acidosis, renal, or hepatic dysfunction for consideration of ECMO (weak recommendation, very low quality evidence)

8. Dallas 2015 Risk of Bias in studies Non-RCT bias asssesment StudyYearDesign Total Patients Population Industry Funding Eligibility Criteria Exposure/Outcome Confounding Follow up Lynch 2011 Non-RCT129 Cardiomyopathy/P re-arrest No Low UnclearLow Song2010Non-RCT81VTNoLow HighLow Eicken2006Non-RCT16AICD patientsNoLow HighLow Greissman1995Non-RCT5IHCANoLow HighLow Teele2011Non-RCT20MyocarditisNoLow HighLow No RCTs Included

9. Dallas 2015 Evidence profile table(s)

10. Dallas 2015 Proposed Consensus on Science statements 1.For the critical outcome of survival to hospital discharge, we have identified no evidence that a specific pre-arrest management strategy in patients with dilated cardiomyopathy (DCM) or myocarditis shows a benefit (Song, 2010, 1951; Eicken, 2006, 30) 2.For the critical outcome of survival to hospital discharge, we have identified no evidence that a specific anesthesia technique in patients with DCM shows benefit. The incidence of cardiac arrest in patient with DCM undergoing procedural anesthesia is low (1.7%). (Lynch, 2011, 951). 3.For the critical outcome of survival with good neurological outcome, we have identified very low quality evidence from an observational study of 12 children with DCM or myocarditis, and documented ventricular tachycardia, that use of ICD or anti- arrhythmic agents may not lead to improved outcome. The risk of inappropriate shock and complications could not be estimated from the study. (Song, 2010, 1951) 4.For the critical outcome of survival to hospital discharge, we have identified very low quality evidence from an observational study of 20 children with acute myocarditis that demonstrated that the use of ECMO may lead to improved outcomes. Cardiac arrest and need for ECMO was associated with those presenting with dysrhythmia, lactic acidosis, renal, or liver dysfunction, (Teele, 2011, 638).

11. Dallas 2015 Draft Treatment Recommendations We suggest that ECMO be used for patients with myocarditis presenting with high risk features (Arrhythmia, Lactic acidosis, Renal and liver dysfunction) and where the appropriate resources for this are available (weak recommendation based on very low quality evidence) There is insufficient evidence upon which to base a recommendation for the empiric use of ICD or anti- arrhythmia medications for children with dilative cardiomyopathy or myocarditis in a pre-arrest state. (weak recommendation based on very low quality evidence)

12. Dallas 2015 Knowledge Gaps Factors associated with cardiac arrest in patients with DCM or myocarditis have not been studied There is little knowledge on benefits of pre- arrest initiation of inotropes/inodilators, mechanical ventilation, or ECMO on survival and neurological outcomes in children with DCM or myocarditis