Background

Acute viral myocarditis (AM) is defined as inflammation of the myocardium heralded by a nonspecific flulike illness. The clinical spectrum in AM varies widely, including asymptomatic patients, patients with signs of moderate heart failure with cardiomegaly on the chest X-ray, and patients with severe heart failure [10, 15]. In contrast, acute fulminant myocarditis (AFM) presents with abrupt onset with severe heart failure, cardiogenic shock, or serious arrhythmias, with echocardiographic evidence of severe left ventricular (LV) dysfunction [2, 7, 17].

Sinus tachycardia, low QRS complex voltage, ST segment elevation, and T-wave inversion are usual EKG changes in early stages of myocarditis [12]. High-grade ventricular ectopy can be life threatening in children with AFM and can predispose to ventricular tachycardia and fibrillation with risk of sudden cardiac death [1, 7]. We report a child with AFM, presented with VT and successfully managed with conventional medical management.

Case Report

A 17-month-old girl, presented with brief history of difficulty of breathing, refusal of food, and irritability for last 18 h. There was no history of fever, cough, gastrointestinal symptoms, or sick contact at home. She has been immunized for age with unremarkable past medical history. She was afebrile, irritable, and toxic looking, with significant respiratory distress. Her vital data included HR 186/min, RR 70/min, and BP 67/28 mmHg. On physical exam, she had basal tachycardia with S3 gallop and feeble peripheral pulses, moderate hepatomegaly, and crackles at both lung bases. Chest X-ray showed moderate cardiomegaly with changes of pulmonary edema. Her EKG demonstrated variable rhythm with wide QRS ventricular tachycardia at rate of 150–160/min to frequent bigemy and occasional sinus rhythm with severe ST segment elevation in lead II, III, aVF, and V4-V6 (Fig. 1) suggestive of myocarditis. Two-dimensional (2D) Doppler echocardiographic study revealed dilated LV with poor systolic function (SF = 14%) and moderate MR/TR. The abnormal baseline labs included elevated cardiac enzymes [CK/CK(MB) 221/24.3 IU/L, Troponin I (0.7 ng/ml), prerenal azotemia (BUN/Cr: 28/0.8), and metabolic acidosis( 15 meq/L). The total and free carnitine levels were (63/20) within normal range. The specimens from nasophyryngeal secretion and rectal swab for viral isolation were submitted.

Fig. 1
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EKG shows ventricular tachycardia with right bundle branch block morphology with superior axis

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Fig. 2
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EKG shows ventricular bigeminy with sinus beats and ST segment elevation in inferior and lateral leads

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She was intubated and sedated on moderate ventilator support. She continued to be hypotensive with poor perfusion after initial fluid resuscitation. Hence, she was placed on low-dose dopamine in view of existing ventricular ectopy, but this was discontinued due to worsening of ventricular tachycardia. She was loaded with 2 mg/kg of amiodarone, followed by continuous infusion at the rate of 10 μg/kg/min. She was also treated with high-dose intravenous immunoglobulin (IVIG) 2 g/kg over the period of 18 h. During the first 24 h, she continued to show frequent premature ventricular contractions (PVC) with bigeminal rhythm and several brief episodes of VT at the rate of 130–140/min, which resolved spontaneously. A repeat echo 48 h after admission showed dilated LV with a SF of 19%. Dopamine was restarted on the second day at a rate of 10 μg/kg/min for low blood pressure and poor urine output. Amiodarone infusion was reduced to 5 μg/kg/min. Ventricular ectopy were less frequent after the fourth day, but she developed significant hepatotoxicity with AST/ALT 4481/5073 IU, PT 20.6 s, and D dimmer >8 (Table 1). Amiodarone was weaned and discontinued and she received free frozen plasma for correction of DIC.

Table 1 Lab data
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She developed right lower-extremity edema with weak dorsalis pulse. Venous Doppler showed deep vein thrombosis (DVT) in the right lower extremity. The right femoral line was removed and started on Lovenox 1 mg/kg every 12 h. Therapy was monitored by serial biochemical analysis of cardiac enzymes, liver enzymes, renal function, coagulation profile, and echo assessment of LV function (Table 1). Her rhythm was consistent sinus after the fifth day. Her liver function test (LFT) and cardiac function improved over the next 5 days. She was extubated after 10 days and started on oro-gastric feeds. The right lower-extremity DVT resolved. She was discharged 15 days after admission, on digoxin, Lasix, Aldectone, Enalapril, and Lovenox. Her serum fibrinogen levels, 6 weeks later, continued to remain low despite of complete recovery of hepatic function (Table 2). She was initially placed on a low dose of Lovenox, considering the strong possibility of dysfibrogenemia. In follow-up, after 36 months, she continues to do well on Enalapril with normal LV systolic function.

Table 2 Hematologic workup
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Discussion

The majority of acute viral myocarditis cases are subclinical and self-limiting in both adults and children [18]. Little information is available on the natural history of AFM in children. Limitations of such reports include the small number of patients, the inclusion of other causes of myocardial dysfunction, the lack of biopsy confirmation of myocarditis, and the failure to distinguish between acute and fulminant myocarditis [10, 14, 15]. A complete recovery is more likely in adults with fulminant compared to acute myocarditis [17] and similar data have been reported recently in children [1].

Inflammatory processes in the cardiac myocytes and interstitium can lead directly to fluctuations in the membrane potential. Fibrosis and scaring of the myocardial tissue and secondary hypertrophy and atrophy of the myocytes favor the development of ectopic pacemakers, late potentials, and reentry as a result of inhomogeneous stimulus conduction. Furthermore, parameters of ventricular dynamics such as increased wall tension, increased myocardial oxygen consumption, and diminished coronary reserve in the case of disturbed systolic or diastolic left ventricular function also contributes to increased incidence of arrhythmias [3, 12, 20].

Infants and children with severe circulatory compromise despite conventional medical intervention might benefit from mechanical support of the circulation using extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD). Temporary circulatory support might allow myocardial recovery or serve as a bridge to transplantation [2, 7, 8, 11].

The administration of IVIG to treat myocarditis has been suggested by its efficacy in other immune-mediated diseases. Its use is also supported by experimental data in which polyclonal immunoglobulin protects against myocardial or arterial damage in mouse models of viral and autoimmune myocarditis [19]. Although no randomized controlled trials of IVIG for the treatment of myocarditis in children have been reported, some clinical evidence suggests it might be beneficial [6, 13]. Steroid treatment seems to benefit a subset of children with ventricular ectopic rhythm and a biopsy diagnosis of myocarditis or borderline myocarditis [3]. Complex ventricular arrhythmias might persist after apparent resolution of occult myocarditis in children requiring long-term antiarrhythmic therapy [9].

High-grade ventricular ectopy should be treated cautiously with antiarrhythmic drugs [5]. Lidocaine infusion is the first-line treatment, given the relative safety. Although amiodarone is widely used to treat ventricular ectopy in adults, the safety profile in children is less well demonstrated. Amiodarone might be proarrhythmic and rapid infusion might precipitate severe hypotension. Acute liver damage after intravenous amiodarone, possibly induced by the solubilizer polysorbate 80, is rare but potentially harmful [16]. Amiodarone loading should therefore be adapted to the necessity of an immediate effect of the drug, and liver function should be monitored closely in critically ill patients. Although there are no pathognomonic histopathological findings, phospholipidosis is the morphologic hallmark of amiodarone hepatotoxicity. In addition to a dose-dependent toxic mechanism, immunogenic or idiosyncratic mechanisms might also play a role in the onset and manifestation of acute liver intoxication by amiodarone. Therapy should be discontinued on the suspicion of cholestatic injury or hepatomegaly [16].

Dysfibrinogenemia is a rare cause of thrombophilia, and other more common causes of thrombophilia should be excluded. The prevalence of congenital dysfibrinogenemia in patients with a history of venous thrombosis has been estimated at 0.8%. Mutation analysis for our patient and her mother showed them to be heterozygous for the A alpha R16C mutation-cysteine instead of arginine at aminoacid 16 of the A alpha-chain, which is the fibrinopeptide A cleavage site. This is the most common mutation and explains the low functional fibrinogen level. Reported cases have been associated with bleeding symptoms (30%) and thrombosis (15%), and the remainder were asymptomatic [4].