Takotsubo cardiomyopathy in a 4-year-old female with pneumococcal meningitis

Abstract

A previously healthy 4-year-old female presented in cardiogenic shock with pneumococcal meningitis. Findings on echocardiogram raised suspicion for takotsubo cardiomyopathy. With supportive care, left ventricular systolic function normalised. Findings on cardiac imaging helped determine the aetiology and avoid further invasive studies or unnecessary treatment.

History of presentation

A previously healthy 4-year-old female presented to an outside hospital in status epilepticus. She was in her usual state of health until one day prior to admission when she developed poor appetite, back pain, and fever. She received rescue antiepileptic medications and was intubated before transfer. Empiric broad-spectrum antibiotics were started. On admission, blood pressure was 86/63 mmHg, heart rate 163, respiratory rate 18, oxygen saturation 100% while mechanically ventilated with FiO₂ 0.45. Physical exam was notable for tachycardia and cold extremities peripherally.

Past medical history

The patient was born at term. Her medical history was notable for recurrent episodes of atypical pneumonia at 2 years of age, anaemia, and SARS-CoV-2 infection a year prior. Vaccinations were up to date. Growth and development were normal. There was no family history of early cardiovascular disease, sudden unexplained death, or cardiomyopathy.

Differential diagnosis

The initial differential diagnosis, considering cardiogenic shock in a child with fever and altered mental status, included myocarditis, sepsis-induced myocardial dysfunction, multisystem inflammatory syndrome in children, new presentation of dilated cardiomyopathy, and takotsubo cardiomyopathy.

Management

Shortly after admission, the patient suffered a rapid decompensation into cardiogenic shock, requiring escalating doses of multiple inotropic and vasopressor agents, but did not require chest compressions. An echocardiogram showed severe left ventricular systolic dysfunction (ejection fraction of 11%) with mid and apical hypokinesis/akinesis and relatively preserved basal myocardial thickening (Supplemental Video S1). Right ventricular systolic function was moderately diminished. Mild tricuspid and mitral valve regurgitation with bilateral ventricular dilation were appreciated. The electrocardiogram was notable for sinus tachycardia, ST depression in the anterior leads, and QTc prolongation (480 ms) (Fig 1). A head CT revealed diffuse cerebral oedema, early findings of anoxic brain injury, and mild tonsillar herniation. Laboratory studies were notable for minimally elevated high sensitivity troponin (145 ng/L (normal <= 13 ng/L)), elevated pro-BNP (9000 pg/mL (normal 30–125 pg/mL)), and elevated inflammatory markers (C-reactive protein 9.1 mg/dL (normal <0.8 mg/dL), procalcitonin 192.32 ug/L (normal <0.15 ug/L)). Viral respiratory panel including COVID-19 was negative; however, SARS-CoV-2 spike antibody was positive. Cerebral spinal fluid gram stain showed gram-positive cocci in pairs concerning for Streptococcus pneumoniae meningitis.

Figure 1. Electrocardiogram from day of hospitalisation 1 showing sinus tachycardia, ST depression in the anterior leads, and QTc prolongation (480 msec).

Due to concern for potential myocarditis, the patient received 2 g/kg intravenous immunoglobulin. Corticosteroids were deferred for concern of infection. One day later, the patient showed improvement in cardiac function with decreased inotropic support, down-trending cardiac markers, and gradual improvement in left ventricular function. A follow-up echocardiogram on the seventh day of hospitalisation off of all hemodynamic support showed complete recovery of left ventricular systolic function and no valvar regurgitation. Despite normalisation of cardiac function, the patient did not recover neurologic function and was declared brain dead.

Discussion

We report a young child presenting in cardiogenic shock with echocardiogram findings consistent with takotsubo cardiomyopathy secondary to severe anoxic brain injury related to pneumococcal meningitis.

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is a form of severe, typically transient, left ventricular systolic dysfunction in the absence of coronary artery disease. It is mostly encountered in post-menopausal women following traumatic emotional or physical injury/stress; however, it has been described in all ages.

The revised Mayo Clinic Criteria for the diagnosis of takotsubo cardiomyopathy in adults include the following:

1. 1. Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid-segments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution, and a stressful trigger is often, but not always, present.

2. 2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture.

3. 3. New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin level.

4. 4. Absence of pheochromocytoma and myocarditis. ¹

The findings on our patient’s echocardiogram, particularly the pattern of dysfunction with relatively preserved basal myocardial contractility with mid and apical hypokinesis/akinesis, are typical of takotsubo cardiomyopathy. ¹ Treatment is supportive, and recovery of left ventricular function is expected. Fulminant myocarditis was also considered, and the patient did receive treatment with intravenous immunoglobulin. However, troponin, which is typically pronounced in the setting of myocarditis, was only minimally elevated, and the electrocardiogram was quite unremarkable. Studies including endomyocardial biopsy and cardiac MRI, which can aid in diagnosing myocarditis, were not employed due to the increased risk of invasive/lengthy procedures in this unstable patient. In this instance, the specific findings on the echocardiogram made takotsubo cardiomyopathy the most likely diagnosis and further invasive studies or unnecessary treatment were deferred.

Takotsubo cardiomyopathy is a rare finding in children with favourable cardiac prognosis. ² Several case reports have been published in children with similar echocardiogram findings in the setting of severe neurologic injury. ^2–9 The included Table 1 outlines these cases. The median duration to recovery was 6.5 days, similar to our case. Of note, only three cases met three or more Mayo Clinical Criteria, highlighting the difficulty in applying adult criteria to children. All patients recovered with supportive care, in some cases requiring mechanical circulatory support.

Table 1. Case reports of children with takotsubo cardiomyopathy associated with brain injury. NR, not reported

In our case, the diagnosis of takotsubo cardiomyopathy was made in the setting of pneumococcal meningitis with severe anoxic brain injury. The pathogenesis of takotsubo cardiomyopathy has been ascribed to high levels of circulating catecholamines, oversaturating cardiac adrenergic receptors leading to increased oxygen demand and myocyte hypoxia. Subsequent metabolic changes during hypoxia include uncoupling of electron transport, affecting ATP synthesis. Release of oxygen-derived free radicals interferes with calcium and sodium transporters, compounding injury to the myocardium. It has been hypothesised that the regional differences in myocardial dysfunction may be explained by the differences in density of beta-1 and beta-2 adrenergic receptors in the apex versus the base of the heart. ¹⁰

Conclusion

Takotsubo cardiomyopathy should be considered in the setting of acute severe brain injury in a child with haemodynamic instability. The specific findings on cardiac imaging described in this report may help determine aetiology and aid in avoiding further invasive studies or unnecessary treatment.