Correlación entre los cambios en el péptido natriurético cerebral y las

características ecocardiográficas en la hipertensión pulmonar persistente del

recién nacido.

Lin Fu & Xiaoshan Zhang Journal of Maternal-Fetal & Neonatal Medicine 2020; Vol 33 (13): 2176 2180.

RESUMEN.

Objetivo:

Investigar la correlación entre los cambios en el péptido natriurético cerebral (BNP) y las

características ecocardiográficas en la hipertensión pulmonar persistente del recién nacido (PPHN).

Pacientes y métodos:

Un total de 76 Los pacientes con HPPRN tratados en nuestro hospital desde marzo de 2017 hasta

febrero de 2018 se dividieron en grupo leve ( n = 33), grupo moderado (n = 22) y grupo severo ( n =

21) según la presión sistólica de la arteria pulmonar, y se compararon con 30 recién nacidos

normales (grupo control) durante el mismo período. Todos los recién nacidos se sometieron a

ecocardiografía, se detectó el nivel de BNP y se analizó la correlación entre las características

ecocardiográficas y los cambios de BNP. <b> Resultados: El nivel de BNP en el grupo control fue

significativamente más bajo que en los grupos PPHN, y fue aumentó constantemente de grupo leve

a grupo severo p <.05). No hubo diferencias significativas en el diámetro auricular izquierdo (LA) y

el diámetro ventricular izquierdo (LV) entre los grupos ( p > .05), mientras que hubo diferencias

significativas en el diámetro auricular derecho (RA), derecha diámetro ventricular (RV) y velocidad

máxima de regurgitación tricuspídea (VTR) ( p <.05). BNP no tenía correlaciones con LA y LV ( p >

.05), pero tenía correlaciones positivas con RA, RV y VTR ( r = 0.527, 0.503 y 0.524, p <.05).

Conclusión:

El nivel de BNP de los pacientes con HPPRN aumenta con la gravedad de la enfermedad. BNP tiene

correlaciones cercanas con las características ecocardiográficas de los pacientes neonatales. La

predicción de los cambios de BNP a través de la ecocardiografía es de cierto valor para guiar el

tratamiento clínico.

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Correlation between changes in brain natriureticpeptide and echocardiographic features inpersistent pulmonary hypertension of newborn

Lin Fu & Xiaoshan Zhang

To cite this article: Lin Fu & Xiaoshan Zhang (2019): Correlation between changesin brain natriuretic peptide and echocardiographic features in persistent pulmonaryhypertension of newborn, The Journal of Maternal-Fetal & Neonatal Medicine, DOI:10.1080/14767058.2018.1543392

To link to this article: https://doi.org/10.1080/14767058.2018.1543392

Published online: 17 Apr 2019.

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ORIGINAL ARTICLE

Correlation between changes in brain natriuretic peptide andechocardiographic features in persistent pulmonary hypertensionof newborn

Lin Fu and Xiaoshan Zhang

Department of Ultrasonic Diagnosis, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China

ABSTRACTObjective: To investigate the correlation between changes in brain natriuretic peptide (BNP)and echocardiographic features in persistent pulmonary hypertension of newborn (PPHN).Patients and methods: A total of 76 patients with PPHN treated in our hospital from March 2017to February 2018 were divided into mild group (n¼ 33), moderate group (n¼ 22) and severe group(n¼ 21) according to the pulmonary arterial systolic pressure, and they were compared with 30 nor-mal newborns (control group) during the same period. All newborns underwent echocardiography,the BNP level was detected, and the correlation between echocardiographic features and BNPchanges was analyzed.Results: The BNP level in control group was significantly lower than those in PPHN groups, andit was constantly increased from mild group to severe group (p<.05). There were no significantdifferences in left atrial diameter (LA) and left ventricular diameter (LV) among groups (p>.05),while there were significant differences in the right atrial diameter (RA), right ventricular diam-eter (RV) and peak velocity of tricuspid regurgitation (VTR) (p<.05). BNP had no correlationswith LA and LV (p>.05), but had positive correlations with RA, RV and VTR (r¼ 0.527, 0.503 and0.524, p<.05).Conclusion: The BNP level of patients with PPHN increases with the increasing severity of dis-ease. BNP has close correlations with echocardiographic features of neonatal patients. Predictingthe BNP changes via echocardiography is of certain value in guiding the clinical treatment.

ARTICLE HISTORYReceived 27 July 2018Revised 9 October 2018Accepted 29 October 2018

KEYWORDSBrain natriuretic peptide;echocardiography; newborn;persistent pulmonaryhypertension

Introduction

Persistent pulmonary hypertension of newborn (PPHN)is a kind of common critical complication in the lung ofneonates, whose mortality rate is as high as about 50%[1]. PPHN is caused by a variety of factors, such asrespiratory distress syndrome, pulmonary vasospasm,pneumonia, aspiration of amniotic fluid and meconium,asphyxia and maternal urinary tract infection in preg-nancy, which is mainly manifested as the pulmonaryarteriolar remodeling, hyperplasia and vasospasm. Theearly clinical symptoms of PPHN are not obvious, andsuch symptoms as severe purpura, faint and respiratoryfailure will occur in the middle-advanced stage [2–4]. InPPHN patients, there are disorders in the pulmonary cir-culation resistance and pressure, and the pulmonaryarterial pressure persistently increases and exceeds thesystemic arterial pressure, thus leading to the right-to-left shunt, and causing the decline in the right ventricu-lar systolic and diastolic functions, dilatation and

hypertrophy. Moreover, the cardiac systolic and diastolicfunctions of the newborn are immature, and the rightheart load increases, thereby leading to the functionaldecline in the right heart, right heart failure and death[5]. The traditional detection means for pulmonaryhypertension is to detect the pulmonary arterial pres-sure using the cardiac catheter, which, however, willresult in vascular injury and myocardial perforation, andit is unbearable especially for newborns. With the con-stant development of echocardiography, it, as a kind ofnoninvasive examination method, has been increasinglyapplied in the clinical diagnosis of PPHN [6]. Brain natri-uretic peptide (BNP) is a kind of polypeptide mainlysecreted by the heart, which can not only regulate bloodpressure and stabilize blood volume, but also directlyreflect the ventricular function, so it is also paid atten-tion to in the field of pediatric research [7]. In this study,BNP detection and echocardiography were performedfor PPHN patients, and the correlation between them

CONTACT Xiaoshan Zhang xiaoshanzhang7ey@163.com Department of Ultrasonic Diagnosis, Affiliated Hospital of Inner Mongolia MedicalUniversity, No. 1 Channel North Street, Huimin District, Hohhot, Inner Mongolia, China� 2019 Informa UK Limited, trading as Taylor & Francis Group

THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINEhttps://doi.org/10.1080/14767058.2018.1543392

was analyzed, so as to provide a basis for the diagnosisand treatment of PPHN.

Materials and methods

General data

A total of 76 patients with PPHN treated in our hospitalfrom March 2017 to February 2018 were selected asobjects of study, and divided into mild group (n¼ 33),moderate group (n¼ 22) and severe group (n¼ 21)according to the pulmonary arterial systolic pressure.PPHN was defined as cyanosis in neonates, which con-tinued after 30min of ventilation with 100% O2 viahood. Patients with hypoxemia with need for supple-mental oxygen for more than 2 d, or any period of inva-sive and noninvasive mechanical ventilation, tomaintain arterial oxygen saturation between 89 and95% were also recruited. At the same time, 30 normalnewborns (control group) were selected for a controlledstudy. The gestational age of the PPHN newborn andcontrols were full term. The systolic pulmonary arterypressure (SPAP) in all patients was >30mmHg, it wasmanifested as sinus rhythm, and patients with hyperten-sion, coronary heart disease, right heart pacemaker,arrhythmia, primary heart disease, right cardiac infarc-tion, organic lesion in tricuspid valve, right ventricularoutflow tract obstruction or pulmonary valve stenosiswere excluded. There were no statistically significant dif-ferences in general data among groups (p>.05), andthey were comparable (Table 1). All subjects signed theinformed consent, and this clinical trial was approvedby the Ethics Committee of Affiliated Hospital of InnerMongolia Medical University.

Methods

Echocardiography

All objects underwent echocardiography at 13 d afterbirth. Newborns in control group were examined inthe ultrasonic diagnosis room, and patients in PPHNgroup were examined at the bedside of the neonatalward. All objects should keep quiet, and newbornswith poor compliance can be fed with breast milk to

be quiet. VIVID 7 color Doppler ultrasound diagnosticinstrument (GE, USA) (frequency: 4–8MHz, samplingvolume: 2mm) was used with the special ultrasonicprobe for children. Under a supine position, trans-thoracic echocardiography was performed, electrocar-diogram was connected synchronously, and theparasternal, apical, subxiphoid and supraclavicularstandard sections were routinely explored and video-recorded. The pulmonary arterial systolic pressure(PASP) of the newborn was measured using the tricus-pid regurgitation pressure gap (TRPG) method:PASP¼ TRPG þ 10mmHg. The left atrial diameter (LA),left ventricular diameter (LV) and right ventriculardiameter (RV) were detected using the M-mode ultra-sonography for the parasternal left ventricular long-axis section, and the diameter of nonoccluded cath-eter and/or oval foramen and right atrial diameter(RA) were detected using the two-dimensional ultra-sonography. The maximum tricuspid regurgitation jeton the apical four-chamber section was measured viacolor Doppler ultrasonography, and the sampling lineand probe angle of continuous wave Doppler wereadjusted based on the jet direction of Doppler ultra-sonography to measure the peak velocity of tricuspidregurgitation (VTR).

Detection of BNP level

After 5mL fasting whole blood was collected from theelbow vein of objects at 6:00 in the morning on thesame day when the echocardiography was performed,it was anticoagulated using heparin and stored in arefrigerator, followed by detection using a biochemicalanalyzer (Hitachi, Japan). The BNP level in the new-born in each group was detected using the immuno-chemical method strictly according to instructions ofthe related kits provided by Roche Diagnostics(Shanghai, People’s Republic of China).

Evaluation criteria

Criteria for PPHN severity [8]: 1) mild: PASP is35–50mmHg, 2) moderate: PASP is 51–70mmHg, and3) severe: PASP is above 70mmHg.

Table 1. Comparisons of general data among groups.

Item

PPHN groups

Control group (n¼ 30) F pMild group (n¼ 33) Moderate group (n¼ 22) Severe group (n¼ 21)

Gender (male/female) 16/17 10/12 10/11 16/14 4.536 <.01Age (d) 7–28 6–28 5–28 5–28 3.278 <.01Average age (d) 14.92 ± 2.29 14.16 ± 2.63 14.97 ± 2.19 14.76 ± 2.08 11.437 <.01Weight 2.95–4.83 2.90–4.85 3.00–5.03 7–28 15.682 <.01Average weight 3.15 ± 0.39 3.13 ± 0.34 3.12 ± 0.33 3.16 ± 0.37 25.493 <.01

2 L. FU AND X. ZHANG

The BNP level in each group was quickly detected usingthe bedside immunochemical method, echocardiographywas performed, and LA, LV, RA, RV and VTR were recorded.

Statistical analysis

Statistical Product and Service Solutions (SPSS) 19.0(SPSS Inc., Chicago, IL, USA) software was used for dataprocessing. Measurement data were presented as mean-± standard deviation, and t test was adopted.Enumeration data were presented as rate, and chi-square test was adopted. Pearson’s correlation coeffi-cient analysis was performed for correlation. p<.05 sug-gested that the difference was statistically significant.

Results

Comparisons of BNP and echocardiographicresults among groups

The BNP level in control group was significantly lowerthan those in three PPHN subgroups, and it was

constantly increased from mild group to severe group(p<.05). There were no significant differences in LAand LV among groups (p>.05), while there were signifi-cant differences in RA, RV and VTR (p<.05) (Table 2).

Correlation between BNP andechocardiographic results

BNP had no correlations with LA and LV (p>.05), buthad positive correlations with RA, RV and VTR in allthree PPHN subgroups (p<.05) (Table 3, Figures 1–5).

Discussion

PPHN often occurs in full-term or post-term infants, butits incidence rate is low in premature infants. The clinicalmanifestations of PPHN include dyspnea, severe purpuraand hypoxemia [9]. At present, there has been no con-sensus yet on the pathogenesis of PPHN, and it is gener-ally believed that PPHN starts from the pulmonaryarteriolar injury, causing dysfunction and abnormalitiesin vascular cytokines and active substances, and leadingto changes and disorders of normal balance of vaso-motor factors. It is manifested as pulmonary vasocon-striction in the initial stage, and develops intopathological changes in pulmonary vascular wall andpulmonary vascular remodeling, eventually leading topulmonary hypertension [10,11]. There are no typicalclinical manifestations of PPHN in the early stage, andmiddle-advanced heart failure has usually occurred oncediagnosed, so the treatment is difficult and the mortalityrate of child patients is higher [12]. However, previousstudies have identified several risk factors for the predic-tion of PPHN, such as low birth weights, patent ductusarteriosus ligation, respiratory support [13,14]. Therefore,the early diagnosis of PPHN is extremely important, andtimely treatment can obviously improve the prognosisof child patients. A noninvasive, simple and accuratemonitoring method is required in clinic due to the par-ticularity of the newborn, so as to provide a basis forclinical diagnosis and treatment.

Echocardiography is an important evaluation meansof cardiac function, which can accurately measure theventricular wall thickness, cardiac chamber size,

Table 2. Comparisons of BNP and echocardiographic results among groups.

Item

PPHN groups

Control group F pMild group Moderate group Severe group

BNP (ng/mL) 625.35 ± 22.48 786.14 ± 23.05 955.18 ± 22.08 404.42 ± 25.13 4.536 < .01LA (mm) 10.89 ± 10.23 11.03 ± 11.27 11.12 ± 1.84 10.92 ± 1.96 3.278 <.01LV (mm) 15.92 ± 1.79 15.86 ± 1.63 15.97 ± 1.69 15.96 ± 1.68 11.437 <.01RA (mm) 14.38 ± 1.16 18.45 ± 1.13 21. 53 ± 1.14 11.28 ± 1.07 15.682 <.01RV (mm) 11.45 ± 0.89 14.53 ± 1.06 16.62 ± 1.13 7.38 ± 0.87 25.493 <.01VTR (m/s) 2.69 ± 0.19 3.62 ± 0.23 4.53 ± 0.28 – 25.493 <.01

Table 3. Correlation between BNP and echocardiographicresults in all three PPHN subgroups.

r P

LA 0.568 .081LV 0.432 .102RA 0.527 .021RV 0.503 .005VTR 0.524 .006

Figure 1. Correlation analysis between BNP and LA.

THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 3

volume and main pulmonary arterial pressure [15].Echocardiography is a noninvasive examinationmethod without radioactivity, and it has been appliedincreasingly more simply with the constant develop-ment of echocardiography techniques. Besides, it canbe performed at the bedside, which is highly applic-able and safe especially for the newborn [16].Echocardiography reflects the pulmonary arterial pres-sure through measuring the blood flow direction andvelocity, and it can be performed repeatedly, so that itcan diagnose and dynamically monitor PPHN. In thenewborn, there is little fat, the chest wall is thin, andthe acoustic window is good, so the ultrasonic imageis satisfactory, well assisting the understanding of theprogression and outcome of disease without adverseeffects [17]. Results of this study revealed that there

were no significant differences in LA and LV amonggroups (p>.05), but there were significant differencesin RA, RV and VTR (p<.05). The reason is that thedevelopment of neonatal sympathetic nerve is imma-ture, the number of sarcomere in the unit volume ofventricular myofiber is small, and the cardiac contract-ility is prone to abnormality under the influence ofexternal factors (asphyxia, infection, etc.). Theincreased pulmonary arterial pressure in PPHN patientswill lead to the increase in right ventricular load, ven-tricular dilatation and involvement of right heart func-tion, so that both ejection and filling time declines,coronary arterial blood perfusion is reduced, and myo-cardial cells are damaged, eventually resulting in thedecline in the whole function of right ventricle andconstantly increasing RA and RV [18]. The decreasedmyocardial contractility in PPHN patients will reducethe rising velocity of right ventricular pressure, andthe tricuspid valve will also increase with the enlarge-ment of right atrium and ventricle, eventually delayingthe opening of the tricuspid valve and closing it inadvance, and increasing the pressure and VTR [19].

Conclusion

BNP is a member of the NP system and the B-type NP,which can promote urine and sodium excretion, exerta potent vasodilatory effect and reflect the cardiacdysfunction [20]. Results of this study manifested thatthe BNP level in control group was significantly lowerthan those in three PPHN subgroups, and it was con-stantly increased from mild group to severe group(p<.05). The reason is that in the early stage of ven-tricular decompensation of PPHN patients, althoughthe systolic function is still normal, large quantities ofBNP will be secreted under the stimulation of pulmon-ary hypertension, and there will be explosive secretionwith the increasing severity of disease [21]. In thisstudy, BNP had no correlations with LA and LV(p>.05), but had positive correlations with RA, RV and

Figure 3. Correlation analysis between BNP and RA.

Figure 2. Correlation analysis between BNP and LV. Figure 5. Correlation analysis between BNP and VTR.

Figure 4. Correlation analysis between BNP and RV.

4 L. FU AND X. ZHANG

VTR (p<.05), indicating that the secretion of BNP isclosely related to RA and RV, because the increase inventricular wall tension and ventricular load is a majorregulator for the production and release of BNP. Whenboth RA and RV constantly increase in PPHN patients,ventricular volume load and ventricular wall tensionwill also increase, thereby greatly activating the NPsystem and leading to the constant release ofBNP [22].

In conclusion, echocardiography can effectivelyevaluate the cardiac function of PPHN patients. BNPcan better reflect the condition of PPHN patients,which is closely related to the characteristics of cardiacfunction displayed by echocardiography, so it is ofgreat value in guiding the clinical treatment of PPHN.

Disclosure statement

No potential conflict of interest was reported by the authors.

References

[1] Vakrilova L. Pulmonary hypertension of the newborn– mechanisms of failed circulatory adaptation afterbirth, clinical presentation and diagnosis. AkushGinekol (Sofiia). 2014;53(3):34–40.

[2] Good RB, Gilbane AJ, Trinder SL, et al. Endothelial tomesenchymal transition contributes to endothelialdysfunction in pulmonary arterial hypertension. Am JPathol. 2015;185(7):1850–1858.

[3] Ghio S, Pica S, Klersy C, et al. Prognostic value ofTAPSE after therapy optimisation in patients with pul-monary arterial hypertension is independent of thehaemodynamic effects of therapy. Open Heart. 2016;3(1):e000408.

[4] Sanchez Mejia AAS, Simpson KE, Hildebolt CF, et al.Tissue Doppler septal Tei index indicates severity ofillness in pediatric patients with congestive heart fail-ure. Pediatr Cardiol. 2014;35(3):411–418.

[5] Kang H, Kim KH, Lim J, et al. The therapeutic effectsof human mesenchymal stem cells primed withSphingosine-1 phosphate on pulmonary artery hyper-tension. Stem Cells Dev. 2015;24(14):1658–1671.

[6] Sivanandam S, Wey A, St Louis J. Intraoperative trans-esophageal echocardiographic assessment of left ven-tricular Tei index in congenital heart disease. AnnCard Anaesth. 2015;18(2):198–201.

[7] Santarelli S, Russo V, Lalle I, et al. Erratum to: useful-ness of combining admission brain natriuretic peptide(BNP) plus hospital discharge bioelectrical impedancevector analysis (BIVA) in predicting 90 days cardiovas-cular mortality in patients with acute heart failure.Intern Emerg Med. 2017;12(4):559–559.

[8] Gosal K, Dunlop K, Dhaliwal R, et al. Rho kinase medi-ates right ventricular systolic dysfunction in rats with

chronic neonatal pulmonary hypertension. Am JRespir Cell Mol Biol. 2015;52(6):717–727.

[9] Wu J, Li C, Yuan W. Phosphodiesterase-5 inhibitionimproves macrocirculation and microcirculation dur-ing cardiopulmonary resuscitation. Am J Emerg Med.2016;34(2):162–166.

[10] Finsterer J, Kothari S. Neonatal pulmonary hyperten-sion in mitochondrial disorders due to TMEM70 muta-tions. Mol Genet Metab Rep. 2014;1(1):235–236.

[11] Yang Q, Sun M, Ramchandran R, et al. IGF-1 signalingin neonatal hypoxia-induced pulmonary hypertension:role of epigenetic regulation. Vascul Pharmacol. 2015;73:20–31.

[12] Sammut P. Long-term mechanical ventilation asadjunctive therapy for children with severe pulmon-ary hypertension. Chest. 2016;149(4):A515–A515.

[13] Bhat R, Salas AA, Foster C, et al. Prospective analysisof pulmonary hypertension in extremely low birthweight infants. Pediatrics. 2012;129(3):e682–e689.

[14] Collaco JM, Dadlani GH, Nies MK, et al. Risk factorsand clinical outcomes in preterm infants with pul-monary hypertension. PLOS ONE. 2016;11(10):e0163904.

[15] Choi YE, Cho HJ, Song ES, et al. Clinical utility ofechocardiography for the diagnosis and prognosis inchildren with bronchopulmonary dsyplasia. JCardiovasc Ultrasound. 2016;24(4):278–284.

[16] Simpson J, Lopez L, Acar P, et al. Three-dimensionalechocardiography in congenital heart disease: anexpert consensus document from the EuropeanAssociation of Cardiovascular Imaging and theAmerican Society of Echocardiography. Eur Heart JCardiovasc Imaging. 2016;17(10):1071–1097.

[17] Hussain AS, Ali R, Ahmed S, et al. Oral sildenafil usein neonates with persistent pulmonary hypertensionof newborn. J Ayub Med Coll Abbottabad. 2017;29(4):677–680.

[18] Cao G, Liu C, Wan Z, et al. Combined hypoxia indu-cible factor-1a and homogeneous endothelial pro-genitor cell therapy attenuates shunt flow-inducedpulmonary arterial hypertension in rabbits. J ThoracCardiovasc Surg. 2015;150(3):621–632.

[19] Al Omar S, Salama H, Al Hail M, et al. Effect of earlyadjunctive use of oral sildenafil and inhaled nitricoxide on the outcome of pulmonary hypertension innewborn infants. A feasibility study. J Neonat PerinatMed. 2016;9(3):251–259.

[20] Dabbagh A, Bastanifar E, Foroughi M, et al. The effectof intravenous magnesium sulfate on serum levels ofN-terminal pro-brain natriuretic peptide (NT pro-BNP)in elective CABG with cardiopulmonary bypass.J Anesth. 2013;27(5):693–698.

[21] K€uc€uko�glu MS, Sinan €UY. The new insights of 2015ESC Pulmonary hypertension Guidelines. Turk KardiyolDern Ars. 2016;44(1):4–8.

[22] Du Y, Fu J, Yao L, et al. Altered expression of PPAR-cand TRPC in neonatal rats with persistent pulmonaryhypertension. Mol Med Rep. 2017;16(2):1117–1124.

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