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Case Report - Acute Enterovirus Myocarditis in the Newborn
Case Report - Acute Enterovirus Myocarditis in the Newborn
Gabriel Altit, Nina Nouraeyan - October 26, 2025.
This late preterm infant was born at 36 weeks’ gestation following induction of labor for suspected chorioamnionitis after the mother presented with fever. The delivery was uncomplicated, and no resuscitation was required at birth. The early neonatal course was unremarkable; however, by the fourth day of life the infant was readmitted for failure to thrive in the context of late prematurity. Screening at that time for respiratory viral infections in the context of sibling with viral syptoms at home revealed positivity for enterovirus/rhinovirus, later confirmed as enterovirus. Over the subsequent days, the infant developed increasing lethargy and respiratory distress, requiring escalation of respiratory support from heated high-flow nasal cannula to continuous positive airway pressure (CPAP). Although chest radiography excluded pneumothorax and pneumonia, mild cardiomegaly was noted.
The infant’s condition progressively deteriorated. Signs of cardiogenic shock emerged, characterized by weak peripheral pulses and poor perfusion. A bedside cardiac point-of-care ultrasound (POCUS), performed with remote support from the Neonatal Hemodynamics (NH-TNE) team at the referring center, revealed markedly depressed left ventricular systolic function. Given the presentation of severe left ventricular dysfunction, most consistent with enterovirus myocarditis, the immediate priority was hemodynamic stabilization and preparation for transfer to a tertiary center with extracorporeal membrane oxygenation (ECMO) capability, should medical management prove insufficient. The infant was admitted to a single-room isolation unit to limit viral exposure to other neonates. Whenever feasible, such infants should be admitted to facilities capable of initiating a pre-ECMO (VA) alert, ensuring that the multidisciplinary team is mobilized in anticipation of potential deterioration. Endotracheal intubation was performed by the most experienced clinician available, recognizing the high risk of cardiovascular collapse during induction. Following intubation, stabilization focused on supporting left ventricular function, minimizing cardiac workload, and reducing metabolic demand. Vascular access was secured, and the infant was kept nil per os, receiving maintenance fluids only, while fluid boluses were avoided because of the marked ventricular dysfunction. Inotropic support was initiated with epinephrine as the first-line agent at 0.05 mcg/kg/min. Epinephrine was preferred for its immediate inotropic effect and relative hemodynamic stability compared with milrinone, which was avoided due to concerns about systemic hypotension, renal impairment, and delayed onset of action in the acute phase. Dobutamine was not started at that point due to its potential risk for tachycardia, increased myocardial oxygen consumption and need for stronger inotropic support.
Prior to transport, essential investigations were completed, including chest radiography, blood gas analysis, lactate, glucose, electrolytes, calcium, creatinine, liver function tests (including albumin and ammonia), coagulation profile, and complete blood count. During stabilization and transport, normothermia, normoglycemia, and normocalcemia were maintained. A bolus of calcium gluconate (50 mg/kg) was administered for its inotropic effect just before departure. Prostaglandins E₁ were initiated in an attempt to reopen the ductus arteriosus and allow the right ventricle to contribute to systemic output, as right ventricular function appeared relatively preserved. Although bedside imaging suggested structurally normal cardiac anatomy, the possibility of missed obstructive lesions, such as supravalvular aortic stenosis or coarctation, needed be fully excluded by formal echocardiography from cardiology. As such, PGE1 were initiated for that reason as well. Other diagnosis that were essential to rule out were anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), or cardio-metabolic conditions requiring genetic therapies (such as replacement with carnithine).
The ductus ultimately failed to reopen, and prostaglandins were discontinued upon arrival at our center (see Echo 1). At that time, the lactate level had improved substantially from >17 mmol/L to 8 mmol/L on epinephrine infusion, respiratory support and some mild sedation/analgesia. At the tertiary center, the infant underwent comprehensive reassessment. Central venous and arterial lines were placed to allow invasive blood pressure monitoring and frequent sampling. Laboratory evaluation included electrolytes, calcium, magnesium, renal and hepatic function studies, coagulation profile, NT-proBNP, and troponin. Echocardiography confirmed severe left ventricular systolic dysfunction and excluded congenital structural heart disease. Consultations were obtained from infectious disease, immunology, and genetics/metabolism teams to evaluate for alternative causes, including hemophagocytic lymphohistiocytosis (HLH), inborn errors of metabolism, mitochondrial disorders, glycogen storage disease, fatty acid oxidation defects, congenital cardiomyopathies, endocrinological conditions and severe sepsis. Carnitine supplementation was initiated empirically. Serial monitoring was performed for lactate, blood gases, NT-proBNP, troponin, creatine kinase, and electrocardiographic changes to guide ongoing management and assess progression. None of the investigations yielded significant alternative findings, and polymerase chain reaction (PCR) testing of nasal secretions confirmed the presence of enterovirus as the causative pathogen.
The anteroposterior chest and abdominal radiograph of this newborn after intubation demonstrates a cardiac silhouette that appears enlarged, occupying more than half of the thoracic width, suggestive of cardiomegaly. Pulmonary vascular markings are mildly prominent but symmetrical. The diaphragms are well defined, and the stomach bubble is visible on the left side.
Sinus rhythm with premature atrial complexes demonstrating aberrant ventricular conduction.
The laboratory trajectory demonstrated a clear pattern of severe, then gradually resolving, myocardial injury and metabolic stress. The earliest samples on arrival showed an elevated lactate of 8.4 mmol/L and a mild acidemia (pH 7.27–7.29), consistent with cardiogenic shock and poor systemic perfusion. Over time, the lactate levels steadily declined—falling to 6.5, then 4.4, and subsequently normalizing to 1–2 mmol/L as perfusion improved. This was paralleled by correction of the metabolic acidosis and stabilization of arterial pH within or slightly above the normal range. Cardiac biomarkers followed a similarly dramatic trajectory. NT-proBNP was >35,000 pg/mL on admission, signifying severe ventricular wall stress and decompensation, while high-sensitivity troponin I was 19,920 ng/L, indicating myocardial injury. Following initiation of inotropic therapy and clinical stabilization, both markers progressively declined over subsequent days, reflecting improving ventricular function and decreasing myocardial strain.
In the days following admission, the patient showed steady clinical improvement and did not require extracorporeal membrane oxygenation. Hemodynamic stability was achieved under low-dose epinephrine, and as myocardial performance improved (see Echo 2), milrinone was introduced for inodilatory support, allowing epinephrine to be gradually weaned and discontinued. Blood polymerase chain reaction testing returned positive for enterovirus, confirming the viral etiology of the myocarditis. During recovery, the infant experienced intermittent runs of ventricular tachycardia and accelerated idioventricular rhythm, along with occasional premature atrial and ventricular contractions. Digoxin was started for rhythm control and to enhance contractility. Within several days of admission, the patient was successfully extubated and transitioned to noninvasive respiratory support before being weaned to room air. Milrinone was tapered and discontinued, while oral therapy with furosemide, digoxin, and captopril was continued to maintain afterload reduction and optimize ventricular function. Serial echocardiograms demonstrated progressive improvement in left ventricular systolic performance, accompanied by improvement of biomarkers including lactate, pH, NT-proBNP, and troponin, consistent with recovering myocardial function after acute viral myocarditis.
Differential Diagnosis of Left Ventricular (LV) Systolic Dysfunction in the Newborn
Differential Diagnosis of Left Ventricular (LV) Systolic Dysfunction in the Newborn
LV systolic dysfunction refers to impaired contractility or the inability of the LV to maintain adequate systemic output, often presenting as heart failure, low cardiac output, or cardiogenic shock in the newborn.
Congenital Obstructive Lesions (Pressure Overload): These conditions significantly increase LV afterload, leading to LV failure and hypokinesis, particularly when the patent ductus arteriosus (PDA) constricts:
Critical Aortic Stenosis (AS) (valvar, subvalvar, or supravalvar): A frequent cause of LV dysfunction and dilatation in the newborn. Severe obstruction may lead to decreased ventricular function and endomyocardial fibroelastosis (EFE) in utero.
Coarctation of the Aorta (CoA) (Severe/Critical): Can cause the left ventricle to rapidly become hypokinetic and lead to LV failure.
Interrupted Aortic Arch (IAA) - Will not necessarily lead to LV systolic failure but will present with significant hypoperfusion in lower limbs at ductal closure, post-ductal hypotension, prolonged refill, acidosis. Eventually, the myocardium is very sensitive to acidosis and contractility will decline.
Hypoplastic Left Heart Syndrome (HLHS): Represents a spectrum of left-sided obstructive lesions (including aortic or mitral atresia/stenosis) that result in a diminutive LV and inadequate systemic circulation. This condition often leads to shock upon ductal closure due to poor systemic output.
Primary and Secondary Myocardial Dysfunction (Cardiomyopathies and Ischemia)
Anomalous Left Coronary Artery from Pulmonary Artery (ALCAPA): The prototype disease of pathological Q waves and myocardial ischemia/infarction in pediatric cardiology. Typically presents around 4–5 weeks of age with congestive heart failure, leading to myocardial ischemia and hypocinetic cardiomyopathy.
Myocarditis (Viral or Idiopathic): Often caused by viruses (Enterovirus/Coxsackievirus B, Echovirus, Adenovirus). Presents as a rapidly progressing, dilated, hypokinetic cardiomyopathy, sometimes with global heart failure and collapse.
Dilated Cardiomyopathy (DCM): The most frequent form of cardiomyopathy. Can be idiopathic, familial/genetic, secondary to maternal auto-antibodies (Anti-Ro/Anti-SSa), or due to inborn errors of metabolism. Left Ventricular Non-compaction (LVNC): Can cause severe LV dysfunction (although some patients with non-compacted LV will be asymptomatic and have normal function).
Hypertrophic Cardiomyopathy (HCM): Can cause severe LV diastolic dysfunction (poor filling and obliteration of the LV cavity). Etiologies include:
Infants of diabetic mothers (IDM).
Genetic syndromes (Noonan's syndrome, Pompe's disease).
Perinatal Stress/Asphyxia/Hypoxic-Ischemic Injury: Can lead to cardiogenic shock and myocardial dysfunction.
Sepsis/Septic Shock: A non-cardiac etiology that commonly causes cardiogenic shock and myocardial dysfunction in extremely preterm infants.
Metabolic/Endocrine Disorders: Hypoglycemia, hypocalcemia, hyper- or hypothyroidism, inborn errors of metabolism (e.g., fatty acid oxidation disorders, Carnitine Transport Deficiency). Other electrolytic anomalies. Selenium Deficiency (TPN).
Coronary Ostial Stenosis/Atresia.
Drugs/Toxins: β-blockers, calcium channel blockers, propofol infusion syndrome, significant vasopressor without inotropic support.
Arrhythmias - Disorders of rhythm that compromise ventricular filling and ejection:
Tachyarrhythmias: Such as sustained supraventricular tachycardia (SVT) or ventricular tachycardia (VT), which can lead to heart failure and shock.
Bradyarrhythmias: Such as Complete Heart Block (CHB).
High Volume/Left-to-Right Shunt Lesions (Volume Overload): These conditions place an excessive volume load on the LV, which, when decompensated, leads to LV failure/dysfunction:
Large Patent Ductus Arteriosus (PDA): A large left-to-right shunt leads to pulmonary overcirculation, left heart dilation (LA and LV dilation), and heart failure. LV dilation may be seen. Typically these patients may present with LV dysfunction upon PDA ligation or cath-based closure due to rapid shift in preload (drop) and afterload (increase). Can lead to coronary steal and myocardial ischemia.
Aortopulmonary Septal Defect (Aortopulmonary Window). Same as PDA and can lead to coronary steal and myocardial ischemia.
Truncus Arteriosus Communis (associated with mild cyanosis and heart failure). Can lead to coronary steal.
Coronary Arteriovenous Fistula (or systemic arteriovenous fistula): Results in a large left-to-right shunt causing rapidly progressive heart failure. Can lead to coronary steal.
Large Ventricular Septal Defect (VSD): Can lead to LV dilation/hypertrophy and signs of heart failure.
Aorto-Left Ventricular Tunnel (ALVT): Can cause low cardiac output and present with signs similar to a large PDA.
Severe Mitral Regurgitation/Dysfunction (e.g., associated with "Neonatal/Infantile" Marfan Syndrome or secondary to LV dilation/ischemia).
RV-LV interdependance
Significant RV dysfunction in the context of pulmonary hypertension (acute or chronic PH)
Congenital Diaphragmatic Hernia (may have a predominant LV dysfunction and/or biventricular dysfunction).
Myocarditis in the Neonatal Period
Myocarditis in the Neonatal Period
Myocarditis is an inflammatory condition affecting the heart muscle, or myocardium. This disease can present with a wide spectrum of severity, from a mild, self-limiting illness to acute decompensated heart failure requiring advanced cardiac support, and can even lead to sudden cardiac death. The primary causes of myocarditis in neonates are largely infectious, with viral infections being the most frequent etiology. Key viral culprits include enteroviruses (such as coxsackievirus and poliovirus), echoviruses, cytomegalovirus, measles, influenza, and adenoviruses. Human Immunodeficiency Virus (HIV) is also listed as a potential cause. Beyond viral agents, bacterial and fungal infections can also lead to myocarditis. Additionally, certain medications can induce myocarditis through hypersensitivity reactions, including various antibiotics (penicillin, cephalosporins, sulfonamides), and diuretics (thiazide, loop diuretics). Rare forms like giant cell myocarditis, characterized by widespread inflammation and myocyte necrosis, are uncommon in children but are often associated with ventricular ectopy and heart block and carry a high fatality rate.
While myocarditis affects children with a bimodal peak incidence—between 6 and 12 months of age and again in adolescence—it is rare in the neonatal population. However, when it does occur in neonates, particularly due to enteroviral infections, the prognosis can be poor, with mortality rates reported as high as 50% in some studies. The clinical presentation of neonatal myocarditis is highly variable, ranging from subtle, non-cardiac symptoms, such as gastrointestinal discomfort, to severe cardiovascular collapse. Sometimes, the initial manifestation may be sudden cardiac arrest, stemming from potential life-threatening arrhythmias. Neonatal myocarditis can closely mimic other critical congenital heart defects, such as aortic and mitral atresia, presenting with acute cardiovascular collapse, pallor, very weak pulses, and severe respiratory difficulty. Infants may show classic signs of heart failure and low cardiac output, including tachycardia, tachypnea, pallor, poor feeding, and inadequate weight gain. On physical examination, a gallop rhythm might be noted, along with a murmur indicative of mitral regurgitation, hepatomegaly, and general signs of poor perfusion. The heart may appear quiet on palpation, often without murmurs, though an apical systolic murmur caused by left ventricular enlargement and mitral insufficiency can be heard. Arrhythmias, particularly multiple ventricular ectopic beats, are also more common in infants with myocarditis.
Diagnosing myocarditis in neonates requires a comprehensive approach, combining a detailed patient history, thorough physical examination, and targeted cardiac investigations. An electrocardiogram (ECG) is a helpful tool, which might show low voltage of the QRS complex across all leads, although right-sided forces can be dominant in very young infants. Other ECG findings may include ST segment depression and T-wave changes in the left precordial leads. Echocardiography is crucial and typically reveals left ventricular dilation and systolic dysfunction. In cases of fulminant myocarditis, a decrease in ventricular function might be observed even without chamber dilation. Pericardial effusion is also a common finding. For a more definitive diagnosis, and to assess for irreversible myocardial damage (necrosis and fibrosis), cardiac magnetic resonance imaging (MRI), especially with gadolinium contrast, is gaining importance in pediatrics and can provide valuable prognostic information regarding functional recovery. Ultimately, an endomyocardial biopsy can confirm the diagnosis of myocarditis but comes with significant risks.
Management of neonatal myocarditis primarily focuses on supportive care. During the acute phase, decreasing myocardial oxygen demand is important and includes: respiratory support, fever control, nutritional support with intravenous nutrition, and judicious use of sedation/analgesia. Anticongestive measures include avoidance of excessive fluid intake, the administration of diuretics (e.g., furosemide) and inotropic agents such as epinephrine for critically ill infants. Digoxin, if used, should be administered with extreme caution and typically at lower dose due to potential patient sensitivity. This should be done in conjunction with a neonatal pharmacists. Identifying the causative virus through viral cultures from blood, stool, or throat swabs, and comparing acute and convalescent serologic titers, is also an important step in guiding management. The role of intravenous immunoglobulin (IVIG) in treatment is still being evaluated, with validation studies currently lacking. Immunosuppression is generally not a routine treatment for myocarditis; it is usually reserved for suspected giant cell myocarditis, especially if frequent ectopy or heart block is present, or for cases of proven autoimmune myocarditis. However, the use of steroids in all patients with suspected myocarditis is still the subject of ongoing debate in the literature. While ECMO or ventricular assist device, as well as heart transplantation are options in severe cases, they are often delayed (when possible) during the acute phase due to the possibility of spontaneous recovery.
The prognosis for neonates with acute viral myocarditis can be severe, with a significant mortality risk. However, many patients, particularly those with milder inflammation, may achieve a complete functional recovery. Unfortunately, approximately 30% of affected individuals may progress to developing chronic dilated cardiomyopathy. In such cases, guideline-directed heart failure therapy, including agents aimed at reverse remodeling, should be initiated if ventricular dysfunction persists.
Insuffisance cardiaque néonatale et cardiomyopathie_eng.pdfPediatric_Heart_Failure_Guidelines_-_Kantor_-_CJC_2013.pdf
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