Preliminary Communication For reprint orders, please contact: reprints@futuremedicine.com NT-proBNP plasma levels as biomarkers for pulmonary hypertension in healthy infants with respiratory syncytial virus infection Moises Rodriguez-Gonzalez* ,1,2 , Isabel Benavente-Fernandez 2,3 , Ana Castellano-Martinez 2,4 , Alfonso Maria Lechuga-Sancho 2,5 & Simon Pedro Lubian-Lopez 2,3 1 Pediatric Cardiology Department, Puerta del Mar University Hospital, C ´ adiz, Spain 2 Biomedical Research and Innovation Institute of C ´ adiz (INiBICA), Research Unit of Puerta del Mar University Hospital, University of C´ adiz, Spain 3 Neonatology Department, Puerta del Mar University Hospital, C ´ adiz, Spain 4 Pediatric Nephrology Department, Puerta del Mar University Hospital, C ´ adiz, Spain 5 Maternal and Child Health and Radiology Department, School of Medicine, University of C ´ adiz, Spain *Author for correspondence: Tel.: +34 956 002 700; doctormoisesrodriguez@gmail.com Aim: To explore NT-proBNP as biomarker for pulmonary hypertension (PH) in infants with respiratory syncytial virus infection (RSVI). Patients & methods: We prospectively enrolled 93 healthy infants with RSVI aged 1–12 months. NT-proBNP determination and echocardiography were performed at admission. Results: PH was found in 22% of patients and associated with a severe course of the disease. NT-proBNP >1635 pg/ml resulted an independent predictor for PH (odds ratio: 16.46 [95% CI: 4.10–66; p < 0.001]). The diagnostic performance of NT-proBNP to detect PH in RSVI was high (area under receiver operator curve of 0.932 [95% CI: 0.883–0.981; p < 0.001]). Conclusions: The presence of PH in healthy infants with RSVI is associated with worse outcomes. NT-proBNP resulted an accurate biomarker for PH in this setting. First draft submitted: 1 October 2018; Accepted for publication: 22 March 2019; Published online: 3 June 2019 Keywords: biomarkers • bronchiolitis • cardiopulmonary interactions • echocardiography • hypoxemia • infants • NT-proBNP • pulmonary hypertension • respiratory acidosis • respiratory syncytial virus Respiratory syncytial virus infection (RSVI) is the most common cause of bronchiolitis in infants and young children worldwide [1]. Although RSVI causes predominantly pulmonary problems, complications involving cardiovascular system are well described [2,3]. Infants with congenital heart diseases, particularly those with associated pulmonary hypertension (PH), have significantly greater morbidity and increased mortality when compared with infants with normal hearts [4,5]. While the mechanisms involved in this greater vulnerability are not completely understood, a diminished cardiopulmonary reserve is suggested in these patients, who do not tolerate well the stress of a pulmonary infection [5]. Myocardial involvement has been observed in previously healthy infants with severe RSVI too. Increased plasmatic cardiac troponin (cTnT) levels have been related to the need of ventilatory or inotropic support in RSVI, suggesting that myocardial strain is clinically significant in these patients [6–11]. Thus, myocarditis with direct myocardial damage by RSVI has been proposed as a possible pathophysiological mechanism in severe cases. However, there is no strong evidence of RSVI-related myocardial inflammation, left ventricular (LV) dysfunction or LV dilation [12,13]. Conversely, the pulmonary disease itself may lead to a raise in pulmonary artery pressures and right ventricular (RV) decompensation in infants with severe RSVI [13,14]. However, cTnT levels have not been correlated with reduced RV function, and PH has been inconsistently reported in this setting [15,16]. Natriuretic peptides (NP) are a family of bioactive peptides released to the circulation from ventricular myocytes in response to ventricular wall stress, that affect sodium and water balance and specifically act to counteract the effects of the renin-angiotensin-aldosterone system [17]. NP has been suggested as potential markers of heart disease and PH in children [18,19]. Moreover, they have been related to myocardial strain in noncardiac diseases, including pulmonary diseases, even without myocardial dysfunction [20–25]. Biomark. Med. (2019) 13(8), 605–618 ISSN 1752-0363 605 10.2217/bmm-2018-0348 C  2019 Future Medicine Ltd