The URI From Hell: Pediatric Myocarditis

By Dr. Al Lulla, MD (PGY-2) and Dr. Melissa Puffenbarger, MD (PEM Attending and US Fellow)

Case

A previously healthy 3-year-old girl presents to the ED with her mother. Her mother reports that she has had a cough and nasal congestion for the past 2 days. She reports she has been sleeping most of the day and “not acting like herself”. She denies her having any fevers at home. Mom also endorses her having a poor appetite and decreased urine output over the past 1-2 days. On arrival to the ED she presents with the following vital signs: T 36.4, P 150, BP 95/63, 98% RA. On exam she is lethargic. She is pale and diaphoretic appearing. She appears tachypneic but does not have any retractions. You identify crackles in the left lower lobe as well as nasal congestion. You identify cool extremities with delayed capillary refill and thready peripheral pulses. Her CBC, BMP and UA are normal, however she has a lactate of 5.5. Chest X-ray demonstrates mild perihilar infiltrates with absence of cardiomegaly. You decide to administer a 20cc/kg normal saline fluid bolus. You obtain blood and urine cultures and start antibiotics. Soon after, you notice that she has worsened tachycardia, altered mental status and now hepatomegaly on exam. Her viral respiratory panel finally comes back positive for coronavirus.

As you notice the child decompensating, you quickly fetch your trusty ultrasound machine to perform a bedside echo. What you notice befuddles you!

Diagnosis

Given what appears to be severe depressed biventricular function on your bedside US, your leading diagnosis is viral myocarditis!

Background

Myocarditis can be described as an inflammatory condition of the heart muscle, which can progress to non-ischemic dilated cardiomyopathy and congestive heart failure [1]. While it has often been considered to be a rare disease, evidence from autopsies in the pediatric patient population indicates that 1.8% of patients have histological evidence consistent with myocarditis, of which 57% of those patients presented with sudden cardiac death [2]. It is thought to have a bimodal age distribution in both infancy and early childhood (<2 years) and in mid-adolescence (14-18 years) [1, 4].

There are a vast array of known causes of myocarditis, which can be broken up into infectious and non-infectious etiologies [3]. In the United States, viral myocarditis is by far the most common; other causes such as drug induced or autoimmune etiologies are exceedingly rare.

The pathophysiology of myocarditis includes three distinct phases [1]:

Phase 1: “Acute” phase, describes viral infiltration and direct injury of the myocardial cells causing necrosis, further potentiating an inflammatory response.
Phase 2: “Subacute” phase, describes the autoimmune reactions mediated by virus-specific T cells, cytokine reaction and antibodies to viral and cardiac proteins. Cardiac contractility decreases.
Phase 3: “Chronic” phase describes the post inflammatory phase characterized by development of dilated cardiomyopathy.

Fulminant myocarditis, which is a terrifying entity of its own, is characterized by sudden onset of cardiogenic shock necessitating aggressive hemodynamic support. Ironically, patients with fulminant myocarditis have overall better long-term prognosis and decreased rates of cardiac transplantation than those with acute, subacute or chronic myocarditis [1].

Clinical Presentation

The presentation of myocarditis varies along a clinical spectrum from minimal symptoms suggestive of a viral syndrome to sudden cardiovascular collapse and death. No symptom is either pathognomonic or common, making the diagnosis of myocarditis extremely challenging for the emergency physician. The most common presenting complaints are: chest pain, shortness of breath, syncope, palpitations, gastrointestinal symptoms (anorexia, abdominal pain, vomiting), poor feeding, URI symptoms, fever and lethargy [1,3].

One study stratified patients with myocarditis as having moderate to severely depressed LV function versus mild-normal depressed LV function and identified that chest pain and respiratory distress were more likely in patients with mild/normal dysfunction compared to those with moderate/severe dysfunction. In addition, the diagnosis can often be elusive in infants who may not be able to verbalize their symptoms. Once again this supports (noticing a theme yet?) that this can be an extremely difficult diagnosis to make [4]. The key here is to always have a high index of suspicion.

On physical exam, patients may be noted to have tachycardia that is out of proportion to their fever. Tachycardia that does not respond to antipyretics or appropriate fluid resuscitation in a patient with viral symptoms warrants further evaluation for myocarditis.

Furthermore, patients may demonstrate evidence of respiratory distress including tachypnea, cyanosis and hypoxia. Patients who have moderate/severely depressed ejection fraction are more likely to show signs consistent with heart failure which include hepatomegaly, gallop, hypotension, edema, pallor and signs of diminished perfusion and end organ dysfunction [1,3,4].

Evaluation: [1,3]

EKG: If there is suspicion of myocarditis, consider ordering an EKG. It’s cheap. It’s fast. Allthough there are no specific findings for myocarditis, many of these patients may have an EKG abnormality, which could help you hone in on a cardiac cause of their illness. EKG abnormalities that may be seen include sinus tachycardia (most common), ventricular hypertrophy, low-voltage QRS complexes and T wave inversions.
CXR: Radiation exposure is bad for children. But one may argue that myocarditis is badder (yes, I know that’s not a real word.). Consider ordering a chest xray in patients requiring increased respiratory support. Chest x-ray findings of pulmonary edema, cardiomegaly or pleural effusion should increase suspicion for myocarditis.
Cardiac Biomarkers: Studies show that troponin levels may be elevated among patients with myocarditis compared to those without myocarditis (sensitivity of 71% and specificity of 86% (when using a troponin T cut off value of 0.052 ng/mL). BNP levels are also more likely to be elevated in patients with myocarditis who have severely depressed LV function. That said, these tests are never diagnostic and should not be used to rule out myocarditis especially if clinical suspicion persists.
Inflammatory Biomarkers: Given the inflammatory milieu created by viral myocardial injury, many patients may have elevated ESR or CRP levels, however these findings are neither sensitive nor specific.
Echocardiography: This is where the money is. Point of care ultrasound in the ED has started to play a significant role in the evaluation of undifferentiated shock in pediatric patients. Patients who have fulminant myocarditis may show global left ventricular or biventricular dysfunction, dilated cardiomyopathy and reduced ejection fraction. If the patient continues to deteriorate consider performing a lung ultrasound to evaluate for B-lines, which represent pulmonary edema (and may appear before the chest xray findings pop up). The utility of bedside ultrasound is that it can rapidly guide your resuscitation and inform you if you should or should not administer fluids to the patient. In the case of the above patient, giving fluids would likely do more harm than good.
Other diagnostics: Cardiac MRI and endomyocardial biopsy (gold standard) may be used as well, but, they have little utility in the acute setting and are not routinely used.

Management

Emergency department management of patients with myocarditis is largely supportive care. Specific therapies may be aimed at volume management, hemodynamic support, and antiarrhythmics in concert with emergent consultation with a pediatric cardiologist. Diuresis, most commonly with furosemide, is a mainstay of therapy and intravenous fluids should be avoided if possible. Afterload reduction can help augment cardiac output. Inotropic support should be considered in all patients with evidence of cardiogenic shock. Preferable agents include milrinone, epinephrine and dobutamine, however norepinephrine and dopamine have also been used historically.

Immunosuppressive agents such as steroids have shown to have no benefit in primary outcome measures including death, transplant-free survival, or improvement in cardiac function. Other agents such as IVIG are considered to be controversial and not recommended in the acute phase of the illness.

Patients who do not improve with pharmacotherapy may require mechanical circulatory support in the form of extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD). ECMO in particular has shown to be successful in the management of patients who require hemodynamic support from myocarditis. One small retrospective study of 28 patients examined outcomes of patients with fulminant myocarditis who were cannulated onto ECMO and found that 46% (n=13) of patients had complete recovery of myocardial function. 21% (n=6) of patients had chronic ventricular dysfunction, another 21% (n=6) underwent cardiac transplantation, and 11% (n=3) died prior to discharge [5]. It is vital to have ECMO resources “on standby” for any ED patient for whom there is concern of myocarditis. (Side note: patients with myocarditis are at high risk for cardiac arrest during intubation. Intubation should be avoided if possible, but in the event that it is needed, having ECMO available may be a lifesaving intervention.)

Despite the fact that a significant proportion of patients will have full recovery with supportive therapies, or ECMO, a small percentage of patients may require cardiac transplantation. VADs are used as a bridge to transplantation, and it is estimated that approximately 88% of patients who are placed on a VAD will survive to receive successful cardiac transplantation [5].

With regards to management the bottom line is: myocarditis is a terrifyingly treatable condition with relatively good outcomes in children, IF you have a high index of suspicion. ED providers can make a huge difference.

Case Conclusion

After the patient was identified as likely having viral myocarditis, she quickly decompensated. She was intubated and then became pulseless. CPR was initiated simultaneously during cannulation with VA ECMO. The patient remained on vasopressor support for an additional 2 days and was successfully decannulated off ECMO 5 days later. She was discharged home on hospital day 21 with a normal ejection fraction. She was started on an ACE inhibitor and was noted to being doing very well at her follow up visit.

Take Home Points

Fulminant myocarditis is a difficult diagnosis to make. The key is to have a high index of suspicion in the ED
The most common etiology of myocarditis is viral in origin
Point of care bedside ultrasound is one of the most important tools in your arsenal. Use it!
Diuretics, vasopressors, and anti-arrhythmics are the mainstays of therapy
Consult a pediatric cardiologist. Consult them early
Patients who fail medical management should be emergently considered for mechanical support in the form of ECMO
Outcomes are favorable when aggressive supportive measures are initiated early

References:

1. Bergmann KR, Kharbanda A, Haveman L. Myocarditis And Pericarditis In The Pediatric Patient: Validated Management Strategies. Pediatr Emerg Med Pract. 2015;12(7):1-22.

2. Weber MA, Ashworth MT, Risdon RA, Malone M, Burch M, Sebire NJ. Clinicopathological features of paediatric deaths due to myocarditis: an autopsy series. Arch Dis Child. 2008;93(7):594-8.

3. Canter CE, Simpson KE, Simpson KP. Diagnosis and treatment of myocarditis in children in the current era. Circulation. 2014;129(1):115-28.

4. Butts RJ, Boyle GJ, Deshpande SR, et al. Characteristics of Clinically Diagnosed Pediatric Myocarditis in a Contemporary Multi-Center Cohort. Pediatr Cardiol. 2017;38(6):1175-1182.

5. Casadonte JR, Mazwi ML, Gambetta KE, et al. Risk Factors for Cardiac Arrest or Mechanical Circulatory Support in Children with Fulminant Myocarditis. Pediatr Cardiol. 2017;38(1):128-134.

The URI from Hell