Heart Failure with Preserved Ejection Fraction in Children without Congenital Heart Disease

HF preserved EF (HFpEF) is not common in children but have been reported in patients with congenital heart disease and open heart surgery. In adult group, acute myocarditis can be presented as HFpEF. We report the HFpEF in children without underlying congenital heart disease, probably associated with acute myocarditis.


Introduction
Heart failure (HF) is usually observed to be caused by failure of ventricular contraction associated with reduced ejection fraction (EF). However, recently, HF with normal EF has become widely reported in adults, with an incidence of 40% to 70% in total HF patients [1]. Until now, only few cases of HF with preserved EF (HFpEF) in pediatric patients have been reported, and most cases of pediatric HFpEF were associated with congenital heart disease and open-heart surgery [2][3][4][5]. Herein, we report a case of HFpEF probably associated with acute myocarditis in children without underlying congenital heart disease.

Case Report
A 9-year-old boy with a 2-month history of abdominal pain was admitted at the Keimyung University Dongsan Medical Center. He had aggravated abdominal pain, dyspnea, orthopnea, facial edema, and weight gain for 3 days. Vital signs were stable without tachypnea. His blood pressure was 120/80 mmHg; pulse rate, 104/min; respiratory rate, 30-36/min, body temperature, 37.0°C; and pulse oximeter saturation, 99% in room air. On physical examination, heart and lung sounds were normal, and no jugular venous distension and hepatosplenomegaly were found. Chest radiography revealed pulmonary edema with both pleural effusions without cardiomegaly (CT ratio, 47.5%; Figure 1). Electrocardiography revealed normal sinus rhythm with no other abnormal finding. The N-terminal pro-B-type natriuretic peptide (NT-proBNP; 3,759 pg/mL) and creatinine kinase-MB levels (4.8 ng/mL) were increased, but the cardiac troponin I level was within the normal range (<0.017 ng/mL). The results of laboratory tests for tuberculosis and rheumatic disease were negative. The level of anti-streptolysin O (1.797 IU/mL) was increased, and polymerase chain reaction showed positive result for Norovirus G II; however, results of other tests for other causative bacteria or virus were all negative.
Echocardiography revealed a normal EF (76.6%) of the left ventricle (LV) with scanty pericardial effusion (3 mm in depth in the parasternal long-axis view). However, the enlarged left atrium (LA; left atrial aortic root ratio [LA/AO]=1.93, LA Z score=5.13) and elevated mitral E/e' ratio (17.2) represented a diastolic LV dysfunction. Cardiovascular magnetic resonance imaging (MRI) revealed normal LV contractility (EF=56%) with pericardial effusion but no evidence of focal myocardial infiltration, myocardial scar, and pericardial disease. However, a mild inflammatory response in the myocardium with edema, especially on the LV apex and anterior wall, was found. He did not undergo cardiac catheterization and cardiac biopsy.
The patient's facial edema and pleural effusion improved after medication with diuretics. He did not complain of respiratory symptoms and was discharged on the ninth day of hospitalization. Serial echocardiography was performed at the outpatient department, and LV systolic and diastolic functions were normal after discontinuation of the medication. The serial laboratory and echocardiographic data are shown in Tables 1 and 2.

Discussion
The diagnostic criteria for HFpEF were as follows: (1) clinical signs or symptoms of HF, (2) evidence of normal or mildly abnormal LV   (3) evidence of abnormal LV diastolic function [6]. The incidence of HFpEF increases with older age and in females as they reach adulthood, with an overall incidence of approximately 1.1% to 5.5% [1]. The predisposing factors of HFpEF in adults were hypertension, atrial fibrillation, and several noncardiovascular diseases such as renal impairment, chronic lung disease, anemia, cancer, liver disease, peptic ulcer disease, and hypothyroidism [1]. HFpEF has been also reported in pediatric groups, including those with congenital aortic stenosis, hypertrophic cardiomyopathy, and restrictive cardiomyopathy [3][4][5]. One study that included pediatric patients who had undergone surgery for congenital heart disease demonstrated a 0.5% incidence of HFpEF [2]. These patients were mainly young children about 1 year of age who had concentric ventricular hypertrophy [2]. Furthermore, these HFpEF patients had significantly higher serum aldosterone levels and higher ratios of aldosterone level to BNP level than patients with HF with reduced EF [2]. In contrast to adult HFpEF, which has a high mortality rate of approximately 55% to 74%, pediatric HFpEF is transient and usually improved spontaneously [1,7].
Myocarditis presents with a wide range of symptoms, from no symptoms to cardiogenic shock [8]. Patients with acute myocarditis usually showed LV systolic failure with chamber enlargement; however, approximately 7% of patients with myocarditis showed LV diastolic failure in the adult group [9]. These patients usually showed infarctlike symptoms, and cardiac MRI is considered for a definite diagnosis of acute myocarditis [8]. Until now, no hypothesis has been proposed for the different presentations of myocarditis, that is, for explaining why some patients with acute myocarditis had diastolic dysfunction rather than the usual course of systolic dysfunction. In the pediatric group, acute myocarditis with restrictive pathophysiology in a 6-year-old patient was reported [10]. The patient showed cardiomegaly and pulmonary edema on chest radiography, and restrictive LV dysfunction on echocardiography, which was confirmed as myocarditis by cardiac biopsy [10]. In our case, we did not perform cardiac biopsy, but the most probable cause of the LV diastolic dysfunction was acute myocarditis depending on cardiac MRI findings.

Conclusion
In conclusion, HFpEF can be found in children without underlying anatomical heart diseases, probably associated with acute myocarditis. In such a case, the subjective symptom was not severe as the usual course of acute myocarditis. LV diastolic failure should be considered in children without underlying anatomical heart diseases.