Neonatal Heart Failure Research Articles

Value of fetal echocardiographic examination in pregnancies complicated by preterm premature rupture of membranes.

Cardiopulmonary and infectious complications are more common in preterm newborns after preterm premature rupture of membranes (pPROM). Fetal echocardiography may be helpful in predicting neonatal condition. Our aim was to assess the cardiovascular changes in fetuses from pregnancies complicated by pPROM and possible utility in predicting the intrauterine or neonatal infection, and neonatal heart failure (HF). It was a prospective study enrolling 46 women with singleton pregnancies complicated by pPROM between 18+0 and 33+6 weeks of gestation and followed until delivery. 46 women with uncomplicated pregnancies served as a control group. Fetal echocardiographic examinations with the assessment of cardiac structure and function (including pulmonary circulation) were performed in all patients. Mean gestational age of pPROM patients was 26 weeks. Parameters suggesting impaired cardiac function in fetuses from pPROM were: higher right ventricle Tei index (0.48 vs. 0.42 p<0.001), lower blood flow velocity in Ao z-score (0.14 vs. 0.84 p=0.005), lower cardiovascular profile score (CVPS), higher rate of tricuspid regurgitation (18.2 % vs. 4.4 % p=0.04) and pericardial effusion (32.6 vs. 0 %). Intrauterine infection was diagnosed in 18 patients (39 %). 4 (8.7 %) newborns met the criteria of early onset sepsis (EOS). HF was diagnosed in 9 newborns. In fetal echocardiographic examination HF group had shorter mitral valve inflow time and higher left ventricle Tei index (0.58 vs. 0.49 p=0.007). Worse cardiac function was observed in fetuses from pPROM compared to fetuses from uncomplicated pregnancies.

Reassessing the role of milrinone in the treatment of heart failure and pulmonary hypertension in neonates and children: a systematic review and meta-analysis.

Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice. • Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. • Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation. • Milrinone may not have a significant inotropic effect. • Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect.

Abstract P1086: Induced Pluripotent Stem Cell-based Cardiac Tissue Modeling Of Mitogenic Cardiomyopathy In Alström Syndrome

Introduction: Cardiomyopathies are a prominent cause of heart failure and affect millions worldwide. Mutation in the Alström syndrome 1 (ALMS1) gene causing Alström syndrome (ALMS) , reported an extremely rare type of dilated cardiomyopathy - called mitogenic cardiomyopathy - leading to neonatal heart failure and death in early infancy due to delayed postnatal cardiomyocyte (CM) cell cycle arrest. Methods: Induced pluripotent stem cells (iPSCs) from ALMS patients with or without mitogenic cardiomyopathy were used to generate ALMS patient-specific cardiomyocytes (iPSC-CMs) . The iPSC-CMs were divided into two main groups based on the presence or absence of the mitogenic phenotype. After transcriptome sequencing, differentially expressed genes (FDR &lt; 0.05, logFC &gt; 0.5 | &lt; -0.5) were found by testing (QL F-test) a robust fitted linear model (edgeR). Harnessing recent advances in stem cell differentiation and tissue engineering, we aimed at creating a human engineered heart tissue model as an unprecedented in vitro disease system to study mechanisms responsible for persistent CM proliferation. Results: ALMS1-deficient mitogenic iPSC-CMs exhibited an impaired ability to undergo cell cycle arrest, evidenced by a higher cell percentage in the G2/M phase (19.3% in mitogenic vs . 7.5% in non-mitogenic iPSC-CMs). Furthermore, increased extracellular matrix levels of the fibroblast-derived protein periostin (POSTN) were observed in co-cultures of ALMS1-deficient iPSC-CMs and ALMS1 fibroblasts. Finally, we found preliminary evidence of dysregulation of the Hippo signaling pathway, observing altered cellular localization of its key downstream effector Yes-associated protein (YAP) and dysregulated ratio between phosphor and total YAP protein levels that in combination with transcript alteration of PPIC, SH3BP4, NTN4, LRIG3 suggest perturbations in YAP signaling in ALMS patients. Conclusion: ALMS1-deficient mitogenic iPSC-CMs recapitulate postnatal proliferation, observed in ALMS patients with mitogenic cardiomyopathy. Preliminary molecular analyses in these in vitro (multicellular) models point to an important role for altered YAP signaling and provide novel cues to enhance CM proliferation, a much-sought objective in cardiac repair.

Mechanisms underlying the efficacy and safety of β-arrestin-biased AT&lt;sub&gt;1 &lt;/sub&gt;agonists as therapeutics for neonatal and infantile heart failure

Mechanisms underlying the efficacy and safety of β-arrestin-biased AT&lt;sub&gt;1 &lt;/sub&gt;agonists as therapeutics for neonatal and infantile heart failure

Abstract 12485: Amniotic Fluid Level of NTproBNP as a Novel Biomarker of Heart Failure in Neonates and Infants

Background and Aim: Recent advances in fetal echocardiography technology and its widespread use have made it possible to evaluate fetal cardiac function and heart failure more accurately, although there is a paucity of clinically useful biomarkers for the diagnosis of heart failure in neonates. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in blood is one of the established biomarkers for heart failure and is known to be reduced exponentially after birth in children born full-term but not in premature infants. Nearly all (95%) NT-proBNP in the blood is excreted in urine. All amniotic fluid is replaced by fetal urine after the second trimester. The aim of this study was to investigate whether amniotic fluid NT-proBNP could be a potentially useful biomarker to assess severity of heart failure in neonates. Methods: We conducted a retrospective cohort study of 13 neonates, including 1 congenital heart disease patient not affected by chromosomal anomalies. We collected peripheral blood, umbilical vein blood, and amniotic fluid to assess each correlations: 1) between levels of umbilical vein blood NT-proBNP (uvNT/cre) and serum NT-proBNP (sNT/cre); 2) between levels of NT-proBNP in amniotic fluid(aNT/cre) and umbilical vein blood NT-proBNP (uvNT/cre); 3) between levels of NT-proBNP in amniotic fluid(aNT/cre) and serum NT-proBNP (sNT/cre). Results: Average gestational age for the subjects was 36±2.0 weeks and average birth weight were 2321.9±557.3g. 2 patients need treatment for heart failure. Our data revealed that there were very strong correlations between uvNT/cre and sNT/cre (R=0.970, p&lt;0.05) as well as between aNT/cre and uvNT (R=0.712, p&lt;0.05), between aNT/cre and sNT (R=0.685, p&lt;0.05) respectively, in neonates. Conclusion: Our data demonstrated that aNT/cre could be a useful biomarker for diagnosing heart failure in neonates/fetuses after the third trimester.

Abstract 11817: Induced Pluripotent Stem Cell-Derived Cardiac Disease Modeling for Studying Mitogenic Cardiomyopathy in Alström Syndrome

Introduction: Cardiomyopathies are a prominent cause of heart failure and affect millions of people worldwide. We reported two case studies describing siblings with a mutation in the Alström 1 (ALMS1) gene causing Alström syndrome (ALMS), who developed mitogenic cardiomyopathy, characterized by delayed postnatal cardiomyocyte (CM) cell cycle arrest resulting in neonatal heart failure and death in early infancy. OBJECTIVES : To generate induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from ALMS patients and investigate molecular mechanisms of persistent CM proliferation in co-culture with ALMS1 fibroblasts. METHODS : We reprogrammed somatic cells from ALMS patients with mitogenic cardiomyopathy into iPSCs using Sendai virus technology and generated ALMS-specific iPSC-CMs using established in vitro differentiation protocols. We analyzed cell cycle progression by determining CM percentages in the G0/G1, S and G2/M phase using flow cytometry, and measured expression and secretion of periostin (POSTN) and collagens from ALMS1 fibroblasts in the extracellular matrix (ECM) using RT-QPCR and western blot. Finally, we investigated Hippo signaling by measuring expression and nuclear translocation of its downstream effectors YAP/TAZ using western blot and immunostaining. RESULTS : iPSC-CMs were successfully generated from ALMS patients and controls. ALMS1-deficient iPSC-CMs exhibited impaired ability to undergo cell cycle arrest, evidenced by a higher cell percentage in the G2/M phase. Furthermore, increased ECM levels of POSTN, a potent regulator of CM proliferation, were observed in co-cultures of ALMS1-deficient iPSC-CMs and ALMS1 fibroblasts. Finally, we found preliminary evidence of dysregulation of the Hippo pathway with altered cellular localization of YAP, and dysregulated total YAP and phosphorylated YAP. CONCLUSION : ALMS1-deficient iPSC-CMs recapitulate persistent postnatal proliferation observed in ALMS patients with mitogenic cardiomyopathy. Increased POSTN in the ECM and altered downstream Hippo signaling contribute to the mitogenic phenotype and suggest critical cues for future therapies aiming at stimulating CM turnover, a much-sought objective in cardiac repair to improve contractile function.

Vein of Galen aneurysmal malformation: rationalizing medical management of neonatal heart failure.

Neonates who present in high output heart failure secondary to vein of Galen aneurysmal malformation can be difficult to manage medically due to the complex physiology that results from the large shunt through the malformation. Though the cardiac function is often normal, right ventricular dilation, severe pulmonary hypertension, and systemic steal can result in inadequate organ perfusion and shock. This report recommends medical management for stabilization of neonates prior to definitive management with endovascular embolization. IMPACT: Vein of Galen aneurysmal malformation (VGAM) is a rare intracranial arteriovenous malformation, which can present in the neonatal period with high output heart failure. Heart failure secondary to VGAM is often difficult to manage and is associated with high mortality and morbidity. Despite optimal medical management, many patients require urgent endovascular embolization for stabilization of their heart failure. This report offers discrete recommendations that can be used by clinicians as guidelines for the medical management of heart failure in newborns with VGAM.

Utility of perinatal natriuretic peptide for predicting neonatal heart failure.

We evaluated the significance of perinatal plasma natriuretic peptide (NP) levels in neonates with congenital heart defects (CHDs) or arrhythmias and determined whether measurement of perinatal plasma NP levels and echocardiographic assessment in utero could predict heart failure after birth. The study was conducted between 2012 and 2016 to evaluate the correlation of perinatal atrial NP (ANP) and brain NP (BNP) levels at birth with the modified Ross score after birth and the cardiovascular profile (CVP) score before birth. A total of 122 singletons with CHDs or arrhythmias and 27 controls were analyzed. Neonatal blood sampling was performed at a median of 0.7 h (range, 0.1-1.5) after birth. The neonatal plasma ANP and BNP levels shortly after birth were significantly higher than those in the umbilical artery (UA) plasma. The ANP and BNP levels in UA and neonatal blood were correlated with the modified Ross score. The neonatal plasma ANP and BNP levels and the modified Ross scores were inversely correlated with the CVP score in neonates with CHDs or arrhythmias. The area under the receiver operating characteristic curve of UA ANP levels for predicting neonatal heart failure was highest among those for the CVP score, perinatal plasma ANP and BNP levels, and their combinations. The plasma ANP and BNP levels increased markedly shortly after birth. Assessment of the UA plasma ANP level at birth and the CVP score in utero may be utilized to predict neonatal heart failure.

The safety of ritodrine hydrochloride: Adverse effects on fetuses and newborns.

Prematurely born infants face unique risks, and the treatment of imminent preterm birth is thus an important part of perinatal care. Ritodrine hydrochloride (Rito) is widely used as a therapeutic agent to treat imminent preterm birth in Japan. Following assessment of the risks and benefits of short-acting β-agonists, including Rito, in Europe, however, the use of Rito has begun to be questioned. Thus, in this study we investigated the safety of Rito in the treatment of imminent preterm birth, with a particular focus on the adverse effects (AEs) on fetuses and newborn infants. Using the Pharmaceuticals and Medical Devices Agency of Japan's Japanese Adverse Drug Event Report (JADER) database, the AEs on fetuses and newborns caused by oral and injected Rito were extracted and analyzed. The reported odds ratios for oral Rito were significantly higher for fetal tachycardia, fetal bradycardia, neonatal hypoglycemia, and neonatal heart failure than for other drugs. The reported odds ratios for Rito injection were significantly higher for fetal tachycardia and neonatal hypoglycemia than for other drugs. Oral drugs had more adverse effect reports than injectable drugs.

Transcatheter Intervention for Coarctation of Aorta: Current Status

Coarctation of aorta (CoA) is an important, treatable cause of heart failure in neonates and of secondary hypertension in adolescents and adults. Surgery has remained as the gold standard in neonates but catheter intervention has usurped it in children, adolescents, and adults. Introduction of covered stents has made the intervention safer. Since it usually appears to be a discrete lesion, at first glance, it attracts interventional cardiologists. However, CoA intervention is associated with significant immediate and long-term complications. Thus, it is imperative for the interventionist to understand the minutiae of the intervention, how to perform it correctly, and how to minimize complications. This review aims to provide complete description of intervention in neonates, adolescents, and adults in one place and also to guide interventional cardiologists perform safer intervention especially in subatretic and atretic CoA.

A novel way of modification of AT1 angiotensin receptors to alleviate neonatal and infantile heart failure

Heart failure is an important cause of death of children. Especially, overt one within the preweaning period is fulminant and severe. However, there are no drugs with evidence for it. We recently found that angiotensin II (AngII) activates L-type Ca2+ channels through AT1 receptors (AT1R) and β-arrestin 2 in murine cardiac myocytes only in the preweaning period, indicating that AT1R/β-arrestin 2 pathway mediates positive inotropic effects before weaning. Indeed, β-arrestin-bias AT1R agonist (BBA), TRV027 caused significant long-lasting positive inotropic effects in preweaning mice without increasing serum aldosterone concentrations or inducing tachycardia, arrhythmias, increased cardiac oxygen consumption, and reactive oxygen species generation. TRV027 increased the peak amplitude of twitch Ca2+ transients not only in preweaning mouse cardiac myocytes but in human iPS cell-derived cardiac myocytes exhibiting the fetal to neonatal phenotype. Moreover, TRV027 also increased contraction of the compromised heart of the model knock-in mice mimicking human congenital dilated cardiomyopathy. Although ~80% of these mice died before weaning, TRV027 significantly increased their survival rate. TRV027 did not cause any obvious adverse effects on their preweaning wildtype littermates. Thus, we reason in this review that BBA can be important therapeutics for preweaning heart failure.

Manipulation of mitochondrial pathways in the neonatal period is associated with enhanced cardiac function

Purpose: Current treatments for neonatal cardiomyopathy and heart failure are non-specific; the use of vasoactive medications and mechanical supports predominate. Recent basic science studies show that embryonic myocytes have less active mitochondria and an immature cellular structure. In addition, the neonatal heart appears to be more closely related in structure to the embryonic/fetal heart with progressive differentiation into its mature form over time. Mitochondria appear to regulate these changes during the neonatal transition. In addition, there appears to be a window in the first week of life, where the neonatal …

Abstract 17290: Tead1 is Required for Cardiomyocyte Proliferation

Introduction: Mammalian cardiomyocyte (CM) proliferation peaks in the embryonic and neonatal periods. TEAD1, a key transcription factor regulated by the Hippo pathway, is critical for early embryonic CM proliferation. But mid gestation lethality of Tead1 germline deletion precluded the study of its role in CMs at later developmental stages. We recently generated Tead1 floxed (Tead1 F/F ) mice which allows the study of TEAD1 function in CMs at later stages. The objective of this study was to determine requirement of TEAD1 for neonatal CM proliferation. Hypothesis: TEAD1 remains critical for CM proliferation in late embryonic and early neonatal periods through transcriptional regulation of cell cycle promoting genes. Methods and Results: We observed that TEAD1 cardiac expression peaks in the perinatal period. Using Myh6-Cre deletor mice, we knocked out Tead1 in CMs at E10.5 (referred as cKO). cKO pups were born in expected Mendelian frequency, but survived only till day of life (DOL) 9. Systolic dysfunction was evident by ECHO in DOL1 cKO pups and progressed to frank heart failure (HF) by DOL9. Histological exam showed decreased myocardial mass with increased intercellular fibrosis. Ventricles of DOL1 cKO pups demonstrated increased expression of Acta1, Nppa, and Nppb, consistent with HF but showed decreased expression of Myh7, suggesting an impairment in the typical fetal gene program activated in HF. Myocardial immunostaining showed reduction in Ki67 (G1/S/G2/M phase marker) (Fig 1) and PH3-S10 (M phase marker) positive CMs by 82% and 46% respectively in DOL1 cKO hearts, indicating significantly reduced CM proliferation. The expression of essential cell cycle proteins showed a significant decrease in the levels of G1/S regulating proteins, CDK4, CDK6, ppRB S807/811 and S/G2 and G2/M regulating proteins, pWEE1 S642 and Cyclin B1 in cKO hearts (Fig 2). Similar results in ex vivo and in vitro Tead1 knockout models in CMs using neonatal Tead1 F/F CMs and HL1 cells validated the cell autonomous regulation of CM cell cycle by TEAD1. Conclusions: TEAD1 is required for embryonic and neonatal CM proliferation and its loss at mid gestation leads to neonatal HF associated with impaired fetal gene program activation and decreased expression of cell cycle promoting genes.

Coarctation of aorta – clinical manifestations and therapeutic options

Coarctation of the aorta (CoA) is congenital heart defect (CHD) in which narrowing of thoracic aorta is typically located at the insertion of the ductus arteriosus just distal to left subclavian artery. This obstruction results in left ventricular pressure overload. CoA accounts for 4 to 6 percent of all CHD. Clinical manifestations of CoA are heart failure in neonates and infants and usually arterial hyperthension and heart murmur in older infants and children. Management of CoA depends on clinical presentation, type of CoA, assosiated heart defects and age. Treatment options are surgery, baloon angioplasty and stent insertion.

Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero.

Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg−/− mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg−/− foetal hearts. CPCs harvested from Speg−/− mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg−/− mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg−/− mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases.

Post-delivery evaluation of morphological change in vein of galen aneurysmal malformation – possible parameter of long-term prognosis

Abstract Vein of Galen aneurysmal malformation (VGAM) is a rare congenital vascular malformation of the central nervous system. Although recent advances in the endovascular treatment and management of neonatal heart failure have resulted in reduced mortality and morbidity, the long-term neurodevelopmental prognosis is not well described. We encounterred a case of prenatally diagnosed VGAM, which was successfully treated, resulting in a favorable neurodevelopmental outcome. In this case, although an emergency intravascular operation was performed due to the post-delivery exacerbation of heart failure, the aneurysmal volume evaluated by magnetic resonance imaging just before the operation was not increased as compared with the prenatal value assessed by ultrasonography. This suggests that the stability of the VGAM volume even under exacerbation of heart failure is a potential parameter to predict the long-term neurodevelopmental prognosis.

Neonatal Death and Heart Failure in Mouse with Transgenic HSP60 Expression.

Mitochondrial heat shock proteins, such as HSP60, are chaperones responsible for the folding, transport, and quality control of mitochondrial matrix proteins and are essential for maintaining life. Both prosurvival and proapoptotic roles have been proposed for HSP60, and HSP60 is reportedly involved in the initiation of autoimmune, metabolic, and cardiovascular diseases. The role of HSP60 in pathogenesis of these diseases remains unclear, partly because of the lack of mouse models expressing HSP60. In this study we generated HSP60 conditional transgenic mice suitable for investigating in vivo outcomes by expressing HSP60 at the targeted organ in disease models. Ubiquitous HSP60 induction in the embryonic stage caused neonatal death in mice at postnatal day 1. A high incidence of atrial septal defects was observed in HSP60-expressing mice, with increased apoptosis and myocyte degeneration that possibly contributed to massive hemorrhage and sponge-like cardiac muscles. Our results showed that neonatal heart failure through HSP60 induction likely involves developmental defects and excessive apoptosis. The conditional HSP60 mouse model is useful for studying crucial biological questions concerning HSP60.

Abstract 092: Transgenic Expression of Heat Shock Protein 60 Results in Neonatal Death and Adult Heart Failure

Heat shock proteins (HSPs) are known for their enhanced expression and pro-survival role in cells under noxious stress. Only recently was it discovered that aberrant expression of HSPs was linked to the onset of cardiovascular diseases. HSP60, originally identified as one of the mitochondrial chaperonins, was shown involved in autoimmune, metabolic, and cardiovascular diseases, but the roles of HSP60 remain unclear in part due to the lack of HSP60 transgenic mouse models. This study aims to investigate the outcome of expressing HSP60 in cardiac tissues to elucidate the role of HSP60 in initiating apoptotic cardiomyopathy. By using a conditional HSP60 transgenic mouse line (G-Lox-HSP60) and a Cre mouse line, human HSP60 expression in most mouse tissues, driven by the ubiquitous CAG promoter, was achieved. The ubiquitous expression of HSP60 was found to cause neonatal death during postnatal day one. In HSP60 expressing newborn mice, hemorrhagic cardiac myopathy was found, and some of these mice exhibited atrium septal defects. A greatly increased rate of apoptosis was found in cardiac tissues with HSP60 overexpression, suggesting a pro-apoptotic role for HSP60. A tamoxifen-inducible Cre mouse (Myh6-Cre/ESR) was used to induce HSP60 expression in the adult mouse heart, and the results showed that dilated heart failure developed within 8 weeks after the induction of HSP60 expression. By employing an isolated perfusion model, the basal contractility was found to be significantly enhanced by HSP60, and a cardiac protection against simulated ischemia and reperfusion injury was found in mice with the HSP60 induction for 4 weeks. Both increased contractility and cardiac protection were lost in mice 6 to 8 weeks after HSP60 induction. Our results showed that HSP60 expression led to heart failure in neonatal mice and likely involved developmental defects and induced apoptosis. While expressing HSP60 in adult cardiac tissues only temporally improved cardiac function and exerted cardiac stress protection, hypertrophy and heart failure eventually occured in these mice. The G-Lox-HSP60 model that achieves expression of HSP60 in an inducible and tissue-specific manner will be useful in studies to investigate the roles and molecular details of HSP60 in various diseases.

Management of an Unusual Left Coronary Artery to Right Ventricular Fistula in a Neonate

Congenital coronary arterial fistula is a rare cause of congestive heart failure in neonates. We describe a neonate who developed early symptoms because of an unusually large left coronary artery to right ventricular fistula. Computed tomography and coronary angiography delineated anatomy and facilitated successful surgical closure.

Value of N-terminal pro-brain natriuretic peptide on evaluating heart failure in neonates with respiratory distress syndrome

Objective To explore the value of plasma N-terminal pro-brain natriuretic peptide(NT-proBNP) in diagnosing or excluding concurrent heart failure (HF) in neonates with respiratory distress syndrome (RDS). Methods One hundred and fifteen preterm infants with RDS, admitted to Neonatal Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from Jan.2011 to Oct.2012, were classified into 2 groups: HF group (56 cases) and non-HF group (59 cases). Differences in cardiac biomarkers and parameters of ultrasonic cardiogram for cardiac function between the 2 groups were analyzed within 24 hours after birth through univariate factors.To evaluate independent factors for HF, logistic regression analysis was performed including significant univariate factors.Receiver operator characteristic curve (ROC) was used to determine the best cutoff for diagnosis of HF with sensitivity and specificity of more than 90%. Results The level of plasma troponin and CK-MB showed no significant difference between the 2 groups(all P>0.05). Compared with the non-HF group, the incidence of patent ductus arteriosus, patent foramen ovale and pulmonary hypertension, as well as plasma NT-proBNP level and pulmonary artery pressure were significantly higher in the HF group(all P<0.05). In contrast, left ventricular ejection fraction and E/A ratio were significantly lower in the HF group(all P<0.05). Logistic regression analysis, which was performed using the 7 significant univariate factors, showed that only plasma NT-proBNP was the independent factor for evaluating HF(OR=1.359, P=0.000). The area under ROC for NT-proBNP levels for diagnosis of HF in RDS neonates was 0.997 (95% CI 0.962-1.000, P=0.000). A cutoff value of at least 16 379 ng/L had a sensitivity of 91.1% and specificity of 98.3%.All the 8 neonates who died had a plasma NT-proBNP level of 35 000 ng/L in 24 hours after birth, significantly higher than that in survival neonates(P=0.000). Conclusions Plasma NT-proBNP level proved to have the value for independently determining or excluding HF in RDS neonates, and dynamic observation for NT-proBNP level may be used for early prediction of mortality risk in neonates with HF. Key words: Respiratory distress syndrome; N-terminal pro-brain natriuretic peptide; Heart failure; Diagnosis