Abstract
In children with physiologically normal hearts, myocarditis is difficult to diagnose and manage due to variable clinical presentation and lack of consensus regarding effective supportive care measures. In those with palliated single ventricle physiology, baseline cardiac function is often altered, and thus, most children receive supportive therapy for congestive heart failure. We theorize that these children are at increased risk of clinically significant impairment in cardiac function in the setting of viral myocarditis.
We present three cases of children diagnosed with hypoplastic left heart syndrome (HLHS) who underwent multi-step surgical palliation. All three children subsequently developed fulminant viral myocarditis later in life, manifesting as symptomatic heart failure and cardiogenic shock. As a result, one child ultimately successfully completed orthotopic heart transplantation, one developed multiple system organ failure, and their care was withdrawn, and one recovered.
Highlights
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Children with congenital heart disease are at risk for viral myocarditis
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Children with congenital heart disease may have worse outcomes and more severe features of myocardial dysfunction.
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Myocarditis can be a precipitating factor in the need for heart transplantation in palliated single ventricle patients
1
Introduction
Acute myocarditis is often precipitated by infection, of which viral infections are the primary etiology. Other common causes include autoimmune, hypersensitivity, malignancy, and exogenous medication- or toxin-mediated myocarditis. Infection or injury of the cardiomyocytes precipitates the body’s innate and adaptive immune responses, leading to immune-cell mediated tissue inflammation and subsequent cardiomyocyte apoptosis [ ]. Little is known or reported about the presentation, causes, and outcomes of viral myocarditis in children with congenital heart disease. Herein, we address the possibility of viral myocarditis as a cause of end-stage heart failure in palliated hypoplastic left heart syndrome.
2
Patient 1
The first child is a 4-year-old male born with HLHS (critical aortic stenosis, mitral valve atresia, and aortic arch hypoplasia) palliated with Norwood operation with Sano modification at 4 days old and subsequent bidirectional superior cavopulmonary anastomosis at 5 months old. Past medical history included feeding intolerance with gastrostomy tube dependence and obstructive sleep apnea. He presented to the emergency department with chest pain and dyspnea with history of viral illness one month prior. Per report, child and caregivers were non-adherent to digoxin and continuous positive airway pressure (CPAP) with sleep. He otherwise was healthy, of normal weight (30th percentile) and motor development for age, and did not have recurrent infections or frequent hospitalizations.
On physical exam, he exhibited hypoxemia with an oxygen saturation of 70 % (baseline 85–90 %), tachycardia (160 bpm), diaphoresis, tachypnea (60 bpm), and pallor. He was normotensive at presentation (98/53). Electrocardiogram (EKG), chest x-ray, and transthoracic echocardiogram were performed; EKG showed new diffuse ST-segment depression in the anterolateral leads when compared to baseline. Chest radiograph was unremarkable, with a stably enlarged cardiomediastinal silhouette. Transthoracic echocardiogram was notable for moderate-to-severely decreased right ventricular systolic function, previously described as mildly depressed prior to admission. Cardiac magnetic resonance imaging (MRI) demonstrated transmural delayed enhancement of the monoventricular free wall, myocardial edema, marked dilatation of the systemic ventricle, and severely reduced ventricular function an approximate ejection fraction of 18 % ( Fig. 1 ). The patient had no prior cardiac MRI for comparison.
On presentation, the laboratory evaluation was notable for respiratory acidosis, acute kidney injury with creatinine of 0.27 mg/dl (baseline 0.2 mg/dl), normal troponin I (0.02 ng/ml), with normal reference values for our institution’s conventional troponin I being <0.06 ng/ml, and elevated brain natriuretic peptide (3480 pg/ml). These values progressed to peak troponin of 59.6 ng/ml on hospital day 3 and peak brain natriuretic peptide of 10,000 pg/ml on hospital day 11. The initial investigative infectious studies include positive Coxsackievirus B3 and B4, parvovirus B19 DNA and IgG, and negative parvovirus B19 IgM serologies. Thus, based on past medical history, clinical presentation, and laboratory confirmation, he was diagnosed with viral myocarditis secondary to parvovirus B19 and Coxsackievirus coinfection.
He was started on milrinone, systemic anticoagulation, intravenous diuresis, and high-flow nasal cannula for hospital days 1–7. He was not treated with intravenous immunoglobulin due to concerns for fluid overload and acute kidney injury. Throughout his hospitalization, he remained milrinone-dependent due to persistent end-diastolic dysfunction and compromised end-organ function. He briefly required an epinephrine infusion to maintain adequate end-organ perfusion, but this was able to be weaned off prior to transplant. His respiratory support was titrated to effect during his hospitalization, with a maximum of high flow nasal cannula and overnight CPAP due to history of obstructive sleep apnea. He did not require mechanical circulatory support in the pre-transplant period. Just prior to transplant, his right ventricular function remained moderately-to-severely decreased, and his fractional area change was calculated to be 17.4 % on echocardiogram. He ultimately received orthotopic heart transplant on hospital day 101 at 5 years old. He was discharged in good condition and persists in good health.
3
Patient 2
The second child was an 8-year-old female born with HLHS (mitral atresia, aortic atresia) palliated with Norwood operation with Sano modification shortly after birth, followed by superior cavopulmonary anastomosis at 6 months of age and inferior cavopulmonary anastomosis at 2.5 years of age. She initially presented to the emergency department with fatigue, nausea, and vomiting and was discharged. Approximately one week later, she presented to cardiology clinic and obtained routine echocardiogram, which showed severely decreased right ventricular systolic function, described as mildly decreased approximately eight months prior at last echocardiogram. She was thus referred to the emergency department and subsequently admitted to the intensive care unit. Her initial troponin on admission was 2.91 ng/ml, and her BNP was 14,600 pg/ml. She was initiated on milrinone and epinephrine infusions upon admission. EKG done at the time of admission showed diffuse ST-segment depression, significantly changed from baseline. Further laboratory data showed elevated titers for adenovirus (confirmed via PCR and blood serology) and coxsackie B3 (confirmed via serology), consistent with viral myocarditis, for which she received intravenous immunoglobulin in two doses during her admission. She received serial echocardiograms during this admission, which demonstrated consistently depressed myocardial function with right ventricular fractional area change of 20–25 % despite clinical improvement. Her nadir of troponin I was 0.57 ng/ml, and NT-proBNP of 5840 pg/ml within 48 h of discharge. Her heart failure was medically managed, and her oral anticongestive regimen was optimized prior to discharge to include aspirin, ACE inhibitor, beta blocker, and diuretic, with total initial length of stay of 18 days.
Three days later, during scheduled cardiology follow-up, she was noted to be lethargic with enophthalmos and poor peripheral perfusion concerning for cardiogenic shock and was readmitted to the intensive care unit. The only symptom relayed by family in the brief intervening period was frequent vomiting. Repeat echocardiogram demonstrated fractional area change of 18.1 % and moderate tricuspid valve insufficiency, which progressed to severe insufficiency on subsequent echocardiograms. Initial lab work was notable for elevated troponin of 6.38 ng/ml and brain natriuretic peptide of 14,800 pg/ml, increased from discharge.
Due to her clinical presentation of acute decompensated heart failure, she underwent evaluation for orthotopic heart transplant. During diagnostic cardiac catheterization, this child experienced cardiac arrest and was cannulated onto extra-corporeal membrane oxygenation (ECMO). While on ECMO, she developed renal failure requiring continuous renal replacement therapy, pulmonary hemorrhage, severe neurologic injury, and liver failure, precluding her from transplant candidacy. Her cardiac and neurological function did not improve, and she was unable to be weaned from mechanical support. The family elected for compassionate withdrawal of care, and she died on hospital day 22.
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Patient 3
The third child is a 2-year-old female born with HLHS (mitral stenosis, aortic atresia) who underwent staged palliation with Norwood operation with Sano modification shortly after birth and superior cavopulmonary anastomosis at 6 months of age. She presented with cardiogenic shock, status epilepticus, and respiratory failure. On admission to the hospital, she was unconscious with active tonic-clonic movements as well as demonstrating hypoxemia (SpO2 61 %), hypertension (129/63 mmHg), tachypnea (70 breaths/min), and hypothermia (35.4C). She was urgently intubated and transferred to the pediatric intensive care unit. Laboratory data showed elevated BNP of 18,700 pg/ml at presentation, which peaked to over 30,000 pg/ml, elevated troponin of 7.77 ng/ml, which peaked to 17.9 ng/ml, as well as metabolic and respiratory acidosis (PCO2 72 mmHg and Lactate 5.4 mg/dl). She was treated with milrinone and epinephrine infusions, as well as intravenous immunoglobulin. Extensive infectious disease evaluation was completed, including, but not limited to, respiratory virus PCR, serologies for coronavirus, CMV, EBV, HSV, influenza, parvovirus, parainfluenza virus, enterorvirus, coxsackie virus, and bacterial blood cultures. The infectious disease workup returned negative. Cardiac MRI was performed on day 2 of admission, which showed dilated systemic right ventricle with severely reduced systolic function with an estimated right ventricular ejection fraction of 19 %. Additionally, the report noted evidence of myocardial and mild pericardial edema in the right and left ventricle on T2 weighted imaging with patchy areas of late gadolinium enhancement in both ventricles and in some of the hypertrophied right ventricle trabeculae and papillary muscles consistent with myopericarditis ( Figs. 2 and 3 ). A brain MRI was also performed, which showed acute embolic infarction in the supratentorial and infratentorial parenchyma. She improved with treatment and was extubated on day 5 of admission. At time of discharge, her single ventricle physiology was supported with aspirin, ACE inhibitor, and digoxin therapies, which were titrated to effect during her hospitalization. Her echocardiogram prior to discharge showed mildly decreased right ventricular systolic function, mild-to-moderate tricuspid regurgitation, and no obvious Glenn anastomosis obstruction with unrestrictive atrial septum. She was discharged after 15 days of hospitalization and remains healthy.
