Contrast echocardiographic assessment of the neonatal ductus arteriosus.

Contrast echocardiography is a safe and accurate method of diagnosing patent ductus arteriosus (PDA) in newborn infants. In this study the presence of PDA in very low birthweight infants receiving mechanical ventilation was investigated by contrast echocardiography. This was used as a basis for determining the accuracy of clinical signs and M mode echocardiography in the diagnosis of PDA. At the first contrast echocardiographic examination at a mean age of 49 hours PDA was found in 75% of infants. Clinical signs were inconsistent; 42% of the infants with PDA at the first examination had a murmur, no relation being found between PDA and heart rate or cardiothoracic ratio. Left atrial and left ventricular dimensions were significantly raised and left systolic time intervals significantly lower in the group with PDA. There was, however, considerable overlap, with the sensitivity of each measurement varying between 52% and 71%. Left systolic time interval combined with left ventricular:aortic root ratio gives the best differentiation between infants with or without PDA.     

Value of systolic time intervals in the diagnosis of large patent ductus arteriosus in fluid-restricted and mechanically ventilated preterm infants

M-mode echocardiographic features suggesting a patent ductus arteriosus are based on two groups of indirect criteria: dilation of the left cardiac cavities and changes of systolic time intervals. The reliability of the first group of criteria has been questioned in fluid-limited, mechanically ventilated preterm infants. The sensitivity of the systolic time intervals in the same circumstances is investigated. Twenty-three patients with a large patent ductus arteriosus were selected. Review of their echocardiograms shows that the sensitivity of the various criteria (expressed as percentage of positivity) was as follows: inversion of the ratio of left ventricular preejection period to right ventricular preejection period, 91.3%; left ventricular preejection period to left ventricular ejection time over right ventricular preejection period to right ventricular ejection time less than 1,83%; left atrium dilation, 74%; shortening of left ventricular preejection period, 70%; dilation of left ventricular internal dimensions in diastole, 65%; increase in left atrium/aorta, 52%; and decrease of left ventricular preejection period to left ventricular ejection time, 48%. Three criteria involving time intervals (left ventricular preejection period to right ventricular preejection period, left ventricular preejection period, and left ventricular preejection period to left ventricular ejection time) had 100% specificity. The lowest specificity was found with criteria involving the left atrium (left atrial to aortic root ratio 75% and left atrium 63%). It is concluded that study of systolic time intervals is a reliable means of detecting preterm infants with hemodynamically significant left-to-right shunt through a patent ductus arteriosus even if the infants are mechanically ventilated and fluid restricted.     

Evaluation of the preterm infant for patent ductus arteriosus

As a first step in a multicenter, collaborative project to study the role of indomethacin in the management of patent ductus arteriosus in premature infants, a diagnostic scheme was developed, on an a priori basis, by a consensus of the participating neonatologists and pediatric cardiologists. The scheme, which utilizes clinical and noninvasive findings, was designed to detect infants with a "hemodynamically significant" patent ductus arteriosus (PDA). Among 1,689 infants with birth weight less than 1,750 g who were monitored during the first year of the study, 342 (20.2%) met the criteria for PDA. Rates were higher for smaller infants (42% with birth weight less than 1,000 g) than for larger infants (7% with birth weight 1,500 to 1,750 g). Although study protocol did not require a direct procedure to confirm the diagnosis of PDA, a marked decrease in the presence of most criteria was noted following surgical ligation of the ductus. Although the echocardiographic criterion (ratio of left atrium to aorta [LA/Ao] greater than or equal to 1.15) proved to have a low specificity for PDA, the data suggest that the overall scheme led to a very low rate of false-positive diagnosis. Following the application of the scheme for 1 year at 13 clinical centers, it has been shown to be a highly acceptable means of detecting infants with PDA.     

近红外光谱技术对有血流动力学意义的动脉导管未闭早产儿肠道组织氧饱和度监测价值的前瞻性研究

目的 使用近红外光谱技术研究有血流动力学意义的动脉导管未闭（hemodynamically significant patent ductus arteriosus,hsPDA）早产儿肠道组织氧饱和度（regional oxygen saturation,rSO₂）的变化及规律,初步探索hsPDA早产儿肠道组织血氧水平变化的临床意义。 方法 前瞻性选取2017年10月至2020年10月深圳市龙岗中心医院新生儿科收治的胎龄<32周和/或出生体重<1 500 g的动脉导管未闭（patent ductus arteriosus,PDA）早产儿。按照hsPDA的诊断标准分为hsPDA组和无血流动力学意义的动脉导管未闭（non-hemodynamically significant patent ductus arteriosus,nhsPDA）组,将hsPDA组早产儿根据口服布洛芬后动脉导管关闭情况分为hsPDA关闭亚组和hsPDA未闭亚组。分别在诊断PDA时及治疗后测定血流动力学指标,持续监测患儿肠道组织rSO₂水平,分析其变化规律。 结果 共有241例PDA早产儿纳入研究,其中hsPDA组55例（22.8%）,nhsPDA组186例（77.2%）;hsPDA关闭亚组36例（65%）,hsPDA未闭亚组19例（35%）。hsPDA组左心房内径/主动脉根部内径值大于nhsPDA组,左室射血分数和短轴缩短率均低于nhsPDA组（P<0.05）。hsPDA组患儿肠道组织rSO₂在诊断后6 h内各时间点（1、2、4、6 h）均低于nhsPDA组（P<0.05）;hsPDA组早产儿肠道组织rSO₂随时间呈下降趋势（P<0.05）,至6 h时达最低值（0.448±0.014）。hsPDA关闭亚组左心房内径/主动脉根部内径值低于hsPDA未闭亚组,左室射血分数和短轴缩短率高于hsPDA未闭亚组（P<0.05）。hsPDA关闭亚组患儿肠道组织rSO₂在治疗后48~96 h内各时间点（48、72、96 h）均高于hsPDA未闭亚组（P<0.05）;hsPDA关闭亚组早产儿肠道组织rSO₂从治疗24 h后随时间呈上升趋势（P<0.05）,至96 h达最高值（0.578±0.031）。 结论 hsPDA对早产儿肠道组织氧合有影响,可通过近红外光谱技术持续监测hsPDA早产儿肠道组织rSO₂变化趋势指导临床管理。     

生后早期床旁心脏超声预测极低出生体重儿动脉导管持续开放的研究(英文翻译)

目的 探讨出生早期床旁心脏超声预测极低出生体重儿（very low birth weight infant,VLBWI）动脉导管持续开放的价值。 方法 回顾性选取2020年3月至2021年6月收治的51例VLBWI为研究对象,入院时日龄≤3 d并且住院时间≥14 d。根据出生14 d及28 d动脉导管未闭（patent ductus arteriosus,PDA）直径大小分为3组：大PDA组（PDA直径≥2 mm）、小PDA组（PDA直径<2 mm）和PDA关闭组（PDA直径=0 mm）,比较3组间生后72 h的心脏超声参数。采用受试者工作特征（receiver operating characteristic,ROC）曲线评估生后72 h心脏超声参数预测生后14 d和28 d动脉导管持续开放（PDA直径≥2 mm）的价值。 结果 生后14 d时,大PDA组有17例,小PDA组11例,PDA关闭组23例;生后28 d时,大PDA组有14例,小PDA组9例,PDA关闭组26例。3组患儿间胎龄、出生体重、肺泡表面活性物质应用及低血压发生率的比较差异有统计学意义（P<0.05）。生后72 h的PDA直径、左肺动脉舒张末期流速、左心室输出量、左心室输出量/上腔静脉血流与生后14 d及28 d时动脉导管持续开放有关（P<0.05）;左心房/主动脉根部直径与生后28 d时动脉导管持续开放有关（P<0.05）。ROC曲线结果显示,生后72 h PDA直径预测生后14 d及28 d动脉导管持续开放的曲线下面积最大,分别为0.841和0.927;其次是左肺动脉舒张末期流速,其曲线下面积分别为0.793和0.833。 结论 生后72 h的床旁心脏超声指标,尤其是PDA直径及左肺动脉舒张末期流速,可预测VLBWI生后14 d和28 d动脉导管持续开放,为后续PDA早期目标性治疗策略的实施提供依据。     

Echocardiographic systolic time intervals in premature infants with patent ductus arteriosus

Summary Thirty-six premature infants with respiratory distress syndrome and clinically significant patent ductus arteriosus (PDA) were studied by M-mode echocardiography before and after closure of the ductus. Before closure the ratio of left ventricular preejection period to left ventricular ejection time (LPEP/LVET) was .26±.03 (mean±SD). After closure of the ductus, LPEP/LVET was .38±.04 (mean±SD), significantly different from the value before closure but not significantly different from the value found in 21 control infants; also, a ratio < .30 was always associated with a clinically significant shunt. The combination of systolic time interval measurement with standard M-mode measurement of the left side of the heart enhanced echocardiographic detection of PDA in our series. Serial evaluation of systolic time interval measurements may provide a further index of left-to-right shunt through a PDA and be a valuable adjunct to the clinical management of these patients.Supported in part by grants from the Kentucky Heart Association.     

The silent ductus arteriosus

Preterm infants at risk of developing a patent ductus arteriosus were followed sequentially by physical examination, echocardiographic determinations of the LA/AO ratio, and chest roentgenograms. The results show that a significant number of infants who have no clinical signs or symptoms of a PDA have large left-to-right shunts. The presence of this shunt was suggested by acute increase in left atrial size by ECHO determination and confirmed by retrograde single-film aortography. Clinical signs and symptoms often developed several days after documentation of the left-to-right shunt.     

A preliminary study of the application of the transductal velocity ratio for assessing persistent ductus arteriosus

OBJECTIVE: To compare the transductal velocity ratio (TVR) of the persistent ductus arteriosus (PDA) with other echocardiographic criteria for haemodynamic significance of a PDA. METHODS: This was a prospective study (from January 1997 to August 1998) in the nurseries of the Royal Women's Hospital, Melbourne. Infants with a clinically suspected PDA were eligible and included if the echocardiogram showed a PDA with a structurally normal heart and the TVR had been measured. The PDA was assessed for evidence of left heart dilatation, the presence of reverse or absent diastolic flow in the descending aorta, the pattern of Doppler flow velocity waveform in the ductus arteriosus, and subjective assessment of ductal diameter on the real time image. The peak systolic velocity (PSV) was obtained from the pulmonary and aortic ends of the PDA, and the TVR calculated by dividing the PSV at the pulmonary end by the PSV at the aortic end. RESULTS: Forty two infants had 59 echocardiographs with their TVR calculated. Mean (SD) birth weight was 1008 (362) g. Mean (SD) gestational age at birth was 27.4 (2.2) weeks with a mean (SD) corrected gestational age of 28.7 (2.7) weeks. The mean TVR was decreased in those infants with a high left atrial diameter/aortic diameter (LA/Ao) ratio (1.9 v 2.8, p = 0.0032) or reverse/absent diastolic flow in the descending aorta (2.1 v 3.0, p = 0.02). This difference was greater if those two criteria were combined (1.7 v 3.4, p = 0.0027). The mean TVR was decreased in infants with a wide open duct seen on two dimensional imaging (1.5 v 3.0, p < 0.0001) or pulsatile flow seen on pulsed Doppler in the PDA (1.9 v 3.4, p = 0.0001). The LA/Ao and left ventricle internal diameter/aortic diameter (LVIDd/Ao) ratios were higher in the group with a TVR < 1.8 than in the other two groups; these differences were statistically significant. CONCLUSIONS: The TVR as a measure of the degree of constriction of a PDA is associated with other echocardiographic criteria for a haemodynamically significant PDA. A low TVR (signifying a poorly constricted duct) is associated with echocardiographic features of a significant left to right shunt, and vice versa. Further research is required to determine the usefulness of the TVR in predicting closure or likely continuing patency of a PDA and the need for treatment.     

Severity of the ductal shunt: a comparison of different markers

BACKGROUND: When the ductus arteriosus (DA) is patent, the ductal shunt is proportional to the ratio of left ventricular output (LVO) to systemic blood flow. Systemic blood flow can be estimated by measuring flow in the superior vena cava (SVC). OBJECTIVE: To re-evaluate the accuracy of standard echocardiographic markers of patent ductus arteriosus (PDA) using LVO/SVC flow ratio. METHODS: Prospective study. Preterm infants of 24-30 weeks gestational age and postnatal age less than 48 hours. The following echocardiographic criteria were measured: left atrial to aortic root ratio (LA/Ao); DA diameter by B mode and colour Doppler; mean and end diastolic flow velocity of the left pulmonary artery (LPA); LVO; SVC flow. RESULTS: Twenty three preterm infants were enrolled (median gestational age 28 weeks (range 24-30), median birth weight 840 g (500-1440)). The DA was closed in eight (mean (SD) LVO/SVC 2.4 (0.3)) and open in 15 (mean (SD) LVO/SVC 4.5 (0.6)). An LA/Ao ratio > or =1.4, a DA diameter > or =1.4 mm/kg, and a mean and end diastolic flow velocity of LPA respectively > or =0.42 and > or =0.20 m/s identified an LVO/SVC > or =4 with a sensitivity and a specificity above 90%. CONCLUSION: This study indicates that LA/Ao ratio, DA diameter, and mean and end diastolic flow velocity of the LPA are accurate markers of PDA. These standard echocardiographic variables are easy to measure and need less skill and resources than direct measurements of ductal shunt.     

Late closure of the ductus arteriosus using indomethacin in the preterm infant

Several studies have shown a lack of effect of indomethacin therapy for the closure of a patent ductus arteriosus (PDA) in premature infants over 14 days of postnatal age. In this report we describe two cases in which a hemodynamically significant PDA was closed with indomethacin in preterm infants over 20 days of age. The response to indomethacin may be more related to postconceptual age than to actual postnatal age. We suggest that intravenous indomethacin therapy should be attempted before surgical ligation is performed in those premature infants under 34 weeks postconceptual age who have a hemodynamically significant patent ductus arteriosus.     

Echocardiographic prediction of patent ductus arteriosus in need of therapeutic intervention

Aim: To evaluate the efficacy of various echocardiographic markers in predicting a patent ductus arteriosus (PDA) in need of treatment. Methods: Forty‐five preterm infants with a mean (SD) gestational age of 27.7 (1.9) weeks underwent echocardiography at a postnatal age of 24 ± 6 and 72 ± 6 h. Four echocardiographic markers were studied: ductus diameter, ductal flow Doppler curves, the left atrial to aortic root (LA/Ao) ratio and Doppler pixels representing ductal shunting. Results: Twenty‐eight infants had a PDA with a detectable left‐to‐right shunt. Of these, 12 (43%) were treated for a shunt through the PDA. Ductal diameter was the most accurate echocardiographic marker when it came to predicting a significant shunt, with a sensitivity of 89%, a specificity of 70%, a positive likelihood ratio of 2.97 and a negative likelihood ratio of 0.16 at the age of 72 h. The efficacy of the method at 72 h of age was 84%. The corresponding efficacy of the pulsatile Doppler curve was 72%, percentage of green colour pixels 63% and the LA/Ao ratio 53%. Conclusion: Ductus diameter appears to be the most important variable in determining the need for therapeutic intervention for PDA in preterm infants.     

Clinical and echocardiographic diagnosis of patent ductus arteriosus in premature neonates

The ductus arteriosus frequently fails to close in premature neonates. Considerable difference in opinion exists around what signifies a hemodynamically significant patent ductus arteriosus (PDA) and how reliable clinical signs are in determining the degree of the left-to-right shunting. Although reliance on clinical signs alone could delay the diagnosis of a PDA, there is insufficient evidence to suggest that early treatment improves outcome. Echocardiography is often used as the gold standard for diagnosing a PDA. A combination of echocardiographic measurements may assist in the early diagnosis of a PDA with a hemodynamically significant degree of left-to-right shunting, especially in extremely premature babies, where closure can be significantly delayed. Decision to treat PDA should be based on a combination of clinical signs and echocardiographic parameters. Monitoring B-type natriuretic peptide may be useful in the diagnosing neonates with symptomatic PDA.     

The critically ill premature infant with patent ductus arteriosus and pulmonary disease-an echocardiographic assessment.

The effect of left-right shunting upon left ventricular and atrial dimensions was assessed by means of 129 serial echocardiographic studies in 37 premature infants with patent ductus arterisus. The cardiac dimensions of asymptomatic premature infants and those with pulmonary disease were similar and served as control subjects. Left cardiac dimensions were enlarged in infants with significant PDA. Dimensions were greatest in surgically treated infants (post-operatively they returned rapidly to normal) in contrast with the persistent enlargement observed in some medically treated infants. Serial echocardiography was a valuable adjunct to clinical assessment of the course of PDA in premature infants with pulmonary disease.     

Atrial natriuretic peptide in patent ductus arteriosus

Plasma concentrations of atrial natriuretic peptide (ANP) were measured in nine infants (age 4 days-9 months) before and after closure of patent ductus arteriosus. Initially all patients had marked distention of the left atrium as indicated by a left atrium to aortic root ratio greater than or equal to 1.3 on echocardiography. After closure of the ductus, operative in six and pharmacological in three patients, left atrial size normalized (left atrium to aortic root ratio less than 1.3) in all patients, except in one treated surgically. Before closure the plasma concentration of ANP was 86-2224 pg/ml and after closure 44-1400 pg/ml. There was a significant correlation between the size of left atrium and plasma concentration of ANP (r = 0.56; p = 0.01). Our results suggest that in infants with patent ductus arteriosus the left atrium is the main source of ANP. The secretory rate of ANP decreases immediately after restoring left atrial size by closure of the ductus.     

Results From Extrapleural Clipping of a Patent Ductus Arteriosus in Seriously Ill Preterm Infants

Minithoracotomy for extrapleural closure of the patent ductus arteriosus (PDA) in seriously ill patients offers a fast and less invasive alternative to conventional transpleural ductal closure. This study reports the immediate postoperative clinical outcomes for 24 extrapleurally clipped premature infants presenting with congestive heart failure in high-risk comorbidity status between March 2007 and November 2010. The demographics, preoperative clinical characteristics, and postoperative outcomes of the patients, including echocardiographic assessments, were evaluated. No surgery-related mortalities occurred. Four mortalities occurred after surgery due to sepsis and bleeding diathesis. All 20 surviving patients exhibited normal left ventricular dimensions and systolic function in the immediate follow-up period. The study shows that extrapleural clip closure in seriously ill premature infants has an acceptable overall short-term mortality and complication rate with a high rate of ductal closure.     

血N端脑钠肽前体在早产儿症状性动脉导管未闭诊治中的应用价值

目的探讨血浆N端脑钠肽前体(NT-pro BNP)在早产儿症状性动脉导管未闭(s PDA)诊治中的临床应用价值。方法选取2013年10月—2014年9月入住新生儿重症监护病房、胎龄28~32周、出生体质量??1 500 g的早产儿107例,分别于生后第4、7天检测NT-pro BNP,采血后30 min内行超声心动图检查。根据生后第4天超声心动图检查结果分PDA组(39例)与对照组(68例);PDA组根据有无超声血流动力学显著改变及临床表现分为症状性PDA(s PDA组,20例)和无症状性PDA(as PDA组,19例);s PDA组再根据是否服用布洛芬分为治疗组(13例)与非治疗组(7例)。结果生后第4天,s PDA组患儿血浆NT-pro BNP水平高于as PDA组,as PDA组高于对照组,差异均有统计学意义(P??0.05);生后第7天,s PDA组患儿血浆NT-pro BNP水平高于as PDA组和对照组,差异有统计学意义(P??0.05),as PDA组与对照组的差异则无统计学意义(P??0.05)。治疗组生后第7天血浆NT-pro BNP水平较第4天显著下降,差异有统计学意义(P??0.05);非治疗组生后第7天与第4天血浆NT-pro BNP水平的差异无统计学意义(P??0.05)。PDA患儿生后第4天血浆NT-pro BNP水平与动脉导管(DA)直径、左心房/主动脉根部内径比值(LA/AO)及DA直径与左肺动脉内径比值(TDD/LPA)呈正相关(r=0.498~0.670,P均??0.05)。生后第4天血浆NT-pro BNP水平预测s PDA的ROC曲线下面积(AUC)为0.969(95%CI:0.938~1.000),NT-pro BNP水平在13 964 pg/m L时,诊断s PDA的灵敏度为95%,特异度为95.4%。结论 s PDA早产儿血浆NT-pro BNP水平明显增高,治疗后下降。第4天血浆NT-pro BNP是预测s PDA的敏感指标,动态监测血浆NT-pro BNP水平变化对指导早产儿PDA治疗策略的选择有重要临床价值。     

不同治疗方式对早产儿动脉导管未闭的疗效及安全性评价

目的 探讨早产儿动脉导管未闭(PDA)的临床治疗方式及效果,总结手术治疗PDA 的经验。方法 2013 年1 月至2014 年12 月诊断为PDA 并行手术治疗的早产儿19 例为手术组,同期未行手术治疗的19 例PDA 早产儿为非手术组。分析两组在病史因素、临床因素、病死率及主要并发症等方面的差异,同时从术前准备及手术结果方面分析手术治疗的特点及临床效果。结果 非手术组早产儿胎龄及出生体重均大于手术组(PP1.3 及导管直径的平方/出生体重(d2/BW)比值>9 mm2/kg 的发生率均高于非手术组(PPP>0.05)。结论 对有临床症状且内科保守治疗或药物治疗无好转的早产儿PDA,外科结扎术是相对安全有效的方法。     

Sensitivity,specificity and predictive value of clinical findings,m-mode echocardiography and continuous-wave Doppler sonography in the diagnosis of symptomatic patent ductus arteriosus in preterm infants

By means of probability analysis we have compared the diagnostic value of clinical symptoms, m-mode echocardiographic measurements and peripheral arterial flow, assessed by continuous-wave Doppler, in preterm infants with symptomatic patent ductus arteriosus (PDA). Data were obtained in 29 infants with PDA and in 29 controls. The most sensitive clinical finding was a hyperactive precordium. Bounding pulses and a heart murmur were absent in 15% and 20%, respectively of the patients with PDA. M-mode echocardiographic measurements were rather specific for the detection of a PDA but less sensitive. Diastolic backflow in the brachial and femoral arteries was present in the majority of patients with PDA and absent in about 67% of the controls. The values in probability analysis, however, were too low to base a therapy on these findings. The highest sensitivity and specificity (100% each) was found for a disturbed cerebral blood flow with absent or retrograde diastolic perfusion estimated by Doppler sonography.Abbreviations PDA patent ductus arteriosus - cw-Doppler continuous-wave Doppler - SF shortening fraction - LPEP/LVET, RPEP/RVET left and right ventricular systolic time intervals - R/F retrograde/forward flow Dedicated to Professor Dr. E. Kleihauer on the accasion of his 60th birthday     

Cardiac effects of a single course of antenatal betamethasone in preterm infants

AIM: To show the effects of a single course of antenatal betamethasone on cardiac measurements and systolic functions in premature newborn infants. METHODS: Seventy six newborn infants with a gestational age of 25-33 weeks were included in the study. They were first classified according to their gestational age: 25-29 weeks (n = 28) and 30-33 weeks (n = 48). They were then reclassified as betamethasone positive (mother received one course of betamethasone) or betamethasone negative (mother did not receive any antenatal glucocorticoid treatment). Cross sectional M mode echocardiographic scans were performed during the first three postnatal days and at the end of the first and third weeks. Left interventricular septum (IVS), left ventricular posterior wall (LVPW), left ventricular end diastolic (LVED), and left ventricular end systolic (LVES) dimensions, aortic root (AO), and left atrial diameters (LAs) were measured. The IVS to LVPW ratio was calculated to identify asymmetrical septal hypertrophy. RESULTS: In neither group was any statistically significant difference noted in IVS, LVED, LVES, LVPW, LA, and AO measurements during the three cardiac ultrasonography scans. Systolic function, as assessed by fractional shortening, was not significantly different in infants who received betamethasone antenatally, in either age group. There was no difference in the IVS/LVPW ratios between those who received antenatal steroid and those who did not for the 25-29 week and 30-33 week groups during these three consecutive scans. CONCLUSION: One course of antenatal betamethasone did not affect the cardiac wall thicknesses and systolic function in premature infants.     

Left ventricular preload reserve in preterm infants with patent ductus arteriosus

The left ventricular Frank-Starling response was studied in 15 preterm infants, less than 1500 g birth weight, and in 16 fullterm infants with patent ductus arteriosus. Left ventricular end diastolic volume (LVEDV), stroke volume, and cardiac output were calculated from biplane echocardiographic images with a modified Simpson's rule, and the left ventricular function curve was obtained by standardising with birth weight and body length. In the relationship between LVEDV and stroke volume, the slope of the regression line was significantly milder in preterm than in fullterm infants; however, there was no significant difference in the relationship between LVEDV and cardiac output. The heart rate was significantly higher in preterm than in fullterm infants. Our data indicated that the premature infants had less left ventricular reserve capacity to respond to the increased preload through the left-to-right ductal shunting than the mature ones, and that the high pulse rate made it possible to generate adequate cardiac output in premature infants.