Pediatric Myocarditis Non-Invasive testing (and ?? Invasive) - PDF document

Goals:  Discuss the spectrum of Myocarditis • Etiology, pathophysiology and presentation  Principles of initial Dx Pediatric Myocarditis • Non-Invasive testing (and ?? Invasive) Diagnosis, Triage and Treatment  How to best safely triage at presentation • What’s the data? • Prediction modeling Jeffrey Gossett, M.D., F.A.A.P.  Principles of initial treatment Director Heart Failure, Heart Transplantation Benioff Children’s Hospitals • HF treatment • ”immuno-modulators”?? • Framework for escalation to MCS? Disclosure Goals:  Discuss the spectrum of Myocarditis  I have no relevant financial relationships with any companies related to the content of this course. • Etiology, pathophysiology and presentation  •  • •  • • • 1 9/4/2018

Trichinella spiralis A Few Definitions from a Dumb Cath Jock  Yikes!!!!!  Myocarditis: • An injury of the myocardium (usually inflammatory) with cell damage and/or degeneration not caused by ischemia  Heart Failure: • The heart isn’t able to do it’s job well enough ‒ Heart failure= imbalance of perfusion/O2 delivery vs. needs  Inadequate C.O. to meet demands Pathogenesis Pathogenesis  Infections (most typical)  Toxin mediated • Drug induced– Anthracyclines other chemo (increasing list)/ radiation • Viral • Toxins (arsenic) ‒ Adenovirus, Enterovirus (Coxsackievirus B, echovirus,  Immune-mediated poliovirus), Parvovirus, HHV-6 • Hypersensitivity ‒ Others; influenza, CMV, HSV, EBV, HIV, RSV etc. • Autoimmune, or collagen–vascular diseases • Probably if we ECHOed everyone with flu all effected….. ‒ SLE, connective tissue disease, rheumatic fever, rheumatoid • Other infections arthritis, and scleroderma, Kawasaki disease, sarcoidosis ‒ Rickettsiae, bacteria, protozoa, parasites, fungi, and yeasts  Idiopathic • Most of the time exact etiology is never found 2 9/4/2018

Pathophysiology Fulminant myocarditis  Viremia with direct viral effect on heart  Acute onset of shock • Virus infects cells, replicates and lyses • Malignant arrhythmias common  Auto-immune effects  Heart is usually SMALL on ECHO • Immune cell infiltration in response to virus/ viral persistence  Highest risk of needing MCS ‒ T-cells, Natural killer cells, Monocytes, Macrophages ‒ Initially beneficial, but can get out of control • BUT full recovery may be more likely • Cytokine release– TNFα, Interferon, interleukins ‒ Balance between beneficial and harmful effects ‒ May directly damage myocytes and depress inotropy  ?? Treatment potential ?? • Myocyte necrosis/fibrosis final pathway Presentation- Chronic, Sub-Acute and Acute Goals:  History– may be very subtle  • Often history of viral disease a few weeks prior (but who doesn’t) •  Symptoms- Very non-specific  Principles of initial Dx • Lethargy, low-grade fever, poor PO, rash, abdominal cx and malaise • Non-Invasive testing (and ?? Invasive) • CHF symptoms  ‒ Diaphoresis, palpitations, dyspnea, exercise intolerance, •  Arrhythmia • • May present with syncope or sudden death   Physical exam findings of congestive heart failure • • Hepatomegally, pallor, JVD, rales, unexplained tachycardia • ‒ May be sinus tachycardia or arrhythmia (SVT/VT) • 3 9/4/2018

Diagnostics Biopsy  HISTORY , HISTORY , HISTORY  Controversial topic IN PEDIATRICS  CXR  Biopsy taken from RV side of ventricular septum • Cardiomegaly, pulmonary congestion • Patchy inflammation with >50% false negatives  ECG– usually abnormal ‒ A mononuclear cell infiltrate is diagnostic of myocarditis • Sinus tachycardia, low voltage QRS, ST/T wave changes, arrhythmias • I DO NOT recommend biopsy routinely  ECHO ‒ Risk/benefit and management decisions does not justify • Poor cardiac function– does not prove etiology  164 pts across 7 centers only 45 (27%) had bx  Viral studies  In large PHIS DB study use fell from 25% in 2006 to 14% in 2011 • Can be difficult to get and interpret– but worth sending - Ghelani et al Demographics, trends, and outcomes in Pediatric Acute Myocarditis in the US 2006-2011 Circ Cardio Qual Outcome (5) 622-627 2012 - Butts et al. Characteristics of Clinically Diagnosed Myocarditis Ped Card (38) 1175-1182 (2017) Diagnostics Gross Pathology  Troponins:  Very patchy process on gross and • Typically abnormal (but how abnormal not useful) microscopic level ‒ VERY high in peri-myocarditis in teenagers • Compared troponin levels in myocarditis vs. dilated cardiomyopathy in pediatric patients ‒ Total of 43 patients– 24 w/ myocarditis  Median for myocarditis was 0.08 vs 0.01 for DCM  Cut off was 0.052 BUT Sensitivity 71%, Specificity 86% -Harris and Gossett Diagnosis and Diagnostic Modalities in Pediatric Patients with Elevate Troponin Ped Card (37) 1469-1474 (2016) -Soongswang et al Cardiac troponin its role in the diagnosis of clinically suspected myocarditis and chronic dilated CM in children Pediatr Cardio (23) 53, 2002 -Soongswang, J. et al. Cardiac Troponin T: A Marker in the Diagnosis of Acute Myocarditis in Children Pediatr Cardiol 26: 45-49, 2005 4 9/4/2018

Biopsy in Myocarditis Goals:   Viral myocarditis •  •  How to best safely triage at presentation • What’s the data? • Prediction modeling   There are exceptions to my rules! • • Giant cell in sarcoidosis • • Auto-immune (lupus etc) • CMR in Myocarditis Presentation  Useful non-invasive assessment  7 large Pediatric Hospitals of myocardial edema  171 total patients • Excellent functional quantification • Bi-modal age distribution • Signs of edema (T2), early  GI symptoms and lower SF contrast enhancement (T1 gad) associated with and late GE death/transplant  50/164 patients (30%) in 7ctr  13% death/transplant study had MRI  PHIS DB study use rose from 5% in 2006 to 28% in 2011  BUT again may not impact rx Butts et al. Characteristics of Clinically Diagnosed Myocarditis Ped Card (38) 1175-1182 (2017) - Ghelani et al Demographics, trends, and outcomes in Pediatric Acute Myocarditis in the US 2006-2011 Circ Cardio Qual Outcome (5) 622-627 2012 - Butts et al. Characteristics of Clinically Diagnosed Myocarditis Ped Card (38) 1175-1182 (2017) 5 9/4/2018

Presentation Presentation of myocarditis  Predictors of worse outcome:  76 patients • Younger patients • From 1/1/07-1/21/16 Patients with Acute Myocarditis • Female gender • 45% High Acuity 33 High-Acuity Cohort • Heart failure/ dec. perfusion • 55% Low Acuity 74 Records Obtained • Worse function 76 41 Low-Acuity Cohort  Worse function at admission predicted worse function at discharge 2 Records Missing • BUT– note the range!!! Pediatric Acute Myocarditis: Predicting Hemodynamic Compromise at Presentation to Healthcare Butts et al. Characteristics of Clinically Diagnosed Myocarditis Ped Card (38) 1175-1182 (2017) Wolf, Chaouki, Marino, Adin-Cristian and Gossett Presented at AHA 2016, paper in process So what to do at presentation?? Triaging myocarditis 21 Inotropic or Vasoactive 2 VAD to Transplant Medications only (1 Death post Transplant) (all received Inotropes/ vasoactive medications)  Retrospective review of patients with myocarditis 6 ECMO 1 Transplant from ECMO 33 High Acuity Cohort • Diagnosed by cardiologist (clinical diagnosis)  We defined 2 cohorts “high acuity” vs “low acuity” 1 VAD ‒ High acuity cohort: All patients who required inotropes, CPR, MCS 3 recovery of function (ECMO or VAD), progressed to transplant or died ‒ Low acuity cohort: Everyone else 4 Transplant • Reviewed signs and symptoms AT presentation ‒ ONLY data collected in first 24hours 1 Death (no VAD/ECMO) Pediatric Acute Myocarditis: Predicting Hemodynamic Compromise at Presentation to Healthcare Pediatric Acute Myocarditis: Predicting Hemodynamic Compromise at Presentation to Healthcare Wolf, Chaouki, Marino, Adin-Cristian and Gossett Presented at AHA 2016, paper in process Wolf, Chaouki, Marino, Adin-Cristian and Gossett Presented at AHA 2016, paper in process 6 9/4/2018