Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10–80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51 ± 21 vs 23 ± 17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45 ± 20 vs 20 ± 17, P < .0001), `idiopathic' PPHN (39 ± 14 vs 14 ± 9, P < .0001), and sepsis (55 ± 25 vs 26 ± 20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI = 41 ± 16 vs 28 ± 18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI = 58 ± 25 vs 46 ± 32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age ≥34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants. Received: 24 April 1997 / Accepted in revised form 3 January 1998     

Inhaled nitric oxide therapy during the transport of neonates with persistent pulmonary hypertension or severe hypoxic respiratory failure

Our aim was to determine whether starting inhaled nitric oxide (iNO) on critically ill neonates with severe hypoxemic respiratory failure and/or persistent pulmonary hypertension (PPH), at a referring hospital at the start of transport, decreases the need for extracorporeal membrane oxygenation (ECMO), lessens the number of hospital days and improves survival in comparison with those patients who were started on iNO only at the receiving facility. The study was a retrospective review of 94 charts of neonates that had iNO initiated by the transport team at a referring hospital or only at the tertiary neonatal intensive care unit (NICU) of the receiving hospital. Data collected included demographics, mode of transport, total number of hospital days, days on inhaled nitric oxide and ECMO use. Of the 94 patients, 88 were included. Of these, 60 were started on iNO at the referring facility (Field-iNO) and 28 were started at the receiving NICU (CHLA-iNO). All patients survived transport to the receiving NICU. Death rates and ECMO use were similar in both groups. Overall, patients who died were younger and had lower birth weights and Apgar scores. For all surviving patients who did not require ECMO, the length of total hospital stay (median days 22 versus 38, P = 0.018), and the length of the hospital stay at the receiving hospital (median days 18 versus 29, P = 0.006), were significantly shorter for the Field-iNO patients than for the CHLA-iNO patients, respectively. Earlier initiation of iNO may decrease length of hospital stay in surviving neonates with PPH not requiring ECMO.     

高频振荡通气、肺表面活性物质联合一氧化氮吸入治疗新生儿低氧性呼吸衰竭的临床研究

目的 探讨用高频振荡通气（HFOV）、肺表面活性物质（PS）联合一氧化氮吸入（iNO）治疗新生儿低氧性呼吸衰竭（HRF）的疗效。方法 116例HRF患儿随机分为三联组和二联组,各58例。三联组采用HFOV、PS联合iNO治疗;二联组采用HFOV 联合iNO治疗。观察两组患儿治疗前及治疗后24 h、48 h的血气分析、PaO2/FiO2（P/F）、OI值和肺动脉压力（PA）的变化,比较不同P/F值、OI值和是否合并PPHN患儿的治疗结局。结果 三联组的上机时间和iNO治疗时间均短于二联组（P<0.01）,且治疗后24 h、48 h的血气指标PaO2 、PaCO2均优于二联组（P<0.01）。三联组合并PPHN的患儿治疗后24 h、48 h的PA值均较二联组下降明显（P<0.01）。在P/F值≤50的病例中,三联组的治愈率优于二联组（P<0.05）;两组死亡者的P/F值均低于存活者（P<0.01）。在OI值≥40的病例中,三联组的治愈率优于二联组（P<0.05）;两组死亡者的OI值均高于存活者（P<0.01）。三联组合并PPHN患儿治愈率优于二联组（P<0.05）。三联组住院时间较二联组缩短（P<0.01）。三联组总治愈率高于二联组（P<0.05）。两组患儿并发症发生率比较差异无统计学意义（P >0.05）。治疗中两组均未监测到严重不良反应。结论 HFOV、PS和iNO三联治疗较HFOV和iNO二联治疗新生儿HRF更为有效,可显著改善氧合,提高患儿的存活率,尤其是为患严重肺部疾病合并PPHN,且P/F值≤50或OI值≥40的病情极危重患儿提供了一个新的治疗手段。     

Early functional echocardiogram and inhaled nitric oxide: usefulness in managing neonates born following extreme preterm premature rupture of membranes (PPROM)

Aim: Poor neonatal outcome of preterm premature rupture of membranes (PPROM) <24 weeks' gestational age (GA) is probably a result of abnormalities in both airway and vascular developments, ventilation perfusion mismatch, and possibly persistent pulmonary hypertension of the newborn (PPHN). Perinatal mortality of 50–90% has been reported in the past, with recent literature reporting significant improvement in neonatal survival. We report our 8‐year experience in this group of infants using early diagnostic functional echocardiography (fECHO), high‐frequency ventilation (HFV) and inhaled nitric oxide (iNO). Methods: The obstetric and neonatal databases were searched to identify babies with PPROM (<20 weeks' gestation) or rupture earlier than 25 weeks for more than 14 days. Results: Twenty‐six infants were identified, of whom 20 were admitted to the neonatal intensive care unit (NICU; mean GA 27.8 weeks, mean birth weight (BW) 1207 g). Early echocardiographic data were available in 12/15 infants requiring mechanical ventilation of whom 10 had evidence of PPHN. All infants who received iNO therapy survived to discharge and only two infants died. Survival to discharge was 69% for the whole cohort of infants and 90% for infants admitted to the NICU. In contrast, for the cohort from pre‐iNO and ‐HFV era, the overall survival to discharge was 62% and 66% for the infants admitted to the NICU. Conclusion: Premature infants with PPROM and presumed severe hypoxemic respiratory failure because of hypoplastic lungs often have significant PPHN and may show improvement in oxygenation after treatment with HFV and iNO. Early fECHO results in earlier identification and treatment of infants with PPHN in this high‐risk group.     

Prevalence of congenital heart defects and persistent pulmonary hypertension of the neonate with Down syndrome

The aim of this study was to assess the prevalence of congenital heart defects (CHDs) and persistent pulmonary hypertension of the neonate (PPHN) in children with Down syndrome (DS) and to assess its impact on neonatal factors. It was a prospective study of a birth cohort of children with DS born between 2003 and 2006 registered by the Dutch Paediatric Surveillance Unit (DPSU). A CHD occurred in 43% of 482 children with trisomy 21. Atrioventricular septal defect was found in 54%, ventricular septal defect in 33.3% and patent ductus arteriosus in 5.8%. The incidence of PPHN in DS was 5.2%, which is significantly higher than the general population (p < 0.001). The reported mortality in newborns with DS was overall 3.3% and was still significant higher in children with a CHD versus no CHD (5.8% versus 1.5%) (p = 0.008). The presence of CHD in children with DS had no influence on their birth weight, mean gestational age and Apgar score. In neonates with DS, we found not only a 43% prevalence of CHD, but also a high incidence of PPHN at 5.2%. Early recognition of the cardiac condition of neonates with DS seems justified.     

Predictors of ECMO Support in Infants with Tachycardia-Induced Cardiomyopathy

The development of tachycardia-induced cardiomyopathy (TIC) is related to the rate and duration of supraventricular tachycardia (SVT). Infants may be more susceptible to TIC because early symptoms might be unrecognized. Extracorporeal membrane oxygenation (ECMO) may improve outcome in patients with SVT and TIC; however, clinical predictors of infants who require ECMO support have not been determined. The purpose of this study was to identify predictors of the need for ECMO in infants with SVT and TIC. Sixteen infants <6 months of age who experienced resolution of TIC following control of arrhythmia were identified. Three patients (19%) required ECMO support. Comparisons were made between patients who required ECMO and those who did not. The groups were similar with respect to age at presentation, type of SVT, rate of SVT, and degree of ventricular dysfunction. However, patients requiring ECMO had increased median M-mode-derived left ventricular end diastolic dimension (LVED) z-score when compared to the medically managed patents (+2.8 vs. 0.0, P = 0.009). No patient in the medically managed group had an LVED z-score >2.3. Infants presenting with SVT and TIC with LVED z-score >2 are at increased risk for requiring ECMO support and early use of ECMO should be considered.     

High frequency oscillatory ventilation and extracorporeal membrane oxygenation in severe persistent pulmonary hypertension of the newborn

We report on 50 term and near-term neonates (birth weight > 1800 g, gestational age > 33 weeks) with severe persistent pulmonary hypertension of the newborn (PPHN), referred to us from January 1987 to July 1991 after failure of maximum conventional treatment. All infants had paO₂<45 mm Hg when ventilated with peak inspiratory pressure >38 cm H₂O and FiO₂=1.0, hence meeting entry criteria for extracorporeal membrane oxygenation (ECMO). High frequency oscillatory ventilation (HFOV) was tried in all patients. If sufficient oxygenation could not be achieved (paO₂<40 mm Hg for at least 2 h), ECMO therapy was begun, which was the case in 25 children. Neonates responding to HFOV (n=25) were of a slightly younger gestational age (37.0 weeks vs 38.8 weeks,P<0.05), had higher Apgar scores and were less hypoxaemic before HFOV (paO₂ 36.6 mm Hg vs 28.8 mm Hg,P<0.01); during HFOV there was a significant rise in paO₂ (> 150 mm Hg;P<0.001) and a fall in pCO₂ to 21.6 mm Hg (P<0.001). Due to air leaks, which was the main complication of HFOV (52%), ECMO therapy had to be begun in two additional infants after an initial positive effect. HFOV tended to be successful in cases of primary PPHN, meconium aspiration and sepsis, but not in infants with lung hypoplasia as a result of diaphragmatic hernia or other reasons. Success or failure of HFOV could not be reliably predicted by any parameter. Mean duration of HFOV was 37.8 h vs 84.9 h of ECMO. PPHN could be overcome in 88% of the HFOV-treated and in 76% of the ECMO-treated infants; overall survival rate was 74% (predicted probability of survival using maximum conventional treatment <10%). There were no significant differences between HFOV/ECMO groups with regard to duration of ventilation following HFOV/ECMO, total time in hospital, rate of bronchopulmonary dysplasia and neurological complications (intracranial haemorrhage, brain infarction). Among the survivors, the rate of mentally handicapped children was equal in both groups (overall 18.9%). Our analysis shows that about 50% of neonates with PPHN who fail to respond to conventional ventilatory support and maximum treatment can be treated successfully with HFOV, thus avoiding ECMO. By applying both forms of therapy, the survival rate of infants with severe PPHN can be increased from an estimated rate of <10% up to 80%.     

Extracorporeal membrane oxygenation use in the first 24 hours following pediatric heart transplantation: Incidence,risk factors,and outcomes

Primary graft dysfunction following HTx is associated with significant morbidity and mortality. This study aimed to assess the incidence of, risk factors for, and outcomes of children requiring ECMO within 24 hours of HTx. This study utilized a linked PHIS/SRTR database of pediatric HTx recipients (2002‐2016). Post‐HTx ECMO was identified using inpatient billing data. Logistic regression assessed risk factors for post‐HTx ECMO. Kaplan‐Meier analyses assessed in‐hospital mortality and post‐discharge survival. A total of 2820 patients were included with 224 (7.9%) requiring ECMO. Independent risk factors for post‐HTx ECMO include age <1 year (aOR: 2.2, 95% CI: 1.3‐3.7, P = 0.006) or 1‐5 years (aOR: 2.1, 95% CI: 1.3‐3.4, P = 0.002), and ECMO support at HTx (aOR: 27.4, 95% CI: 15.2‐49.6, P < 0.001). Survival to discharge decreased with increasing duration of post‐HTx ECMO support; 89% for 1‐3 days, 79.1% for 4‐6 days, 63.2% for 7‐9 days, and 18.8% for ≥10 days. There was no difference in long‐term survival for patients requiring post‐HTx ECMO who survived to hospital discharge (P = 0.434). There are identifiable risk factors associated with the need for ECMO in the post‐HTx period. Length of time on ECMO post‐HTx is strongly associated with the risk of in‐hospital mortality. Patients who require ECMO early post‐HTx and survive to discharge have comparable outcomes to patients who did not require ECMO.     

Outcome in neonates with congenital heart disease referred for respiratory extracorporeal membrane oxygenation

AIM: To evaluate the proportion of neonates referred for extracorporeal membrane oxygenation (ECMO) support in the modern era of advanced conventional treatments for respiratory failure who actually had congenital heart disease (CHD), and to assess the impact of this diagnostic route on patient condition and outcome. METHODS: A retrospective case-note review of neonatal ECMO and cardiac admissions to a single, tertiary ECMO and cardiac intensive care unit (ICU) between March 1999 and February 2002. RESULTS: 287 symptomatic neonates presented to the ICU with previously undiagnosed cardiac or respiratory disease. Eighty-two with presumed respiratory failure were referred for ECMO, and 205 with suspected CHD were referred for cardiac evaluation. Eight (10%) ECMO referrals, all with presumed persistent pulmonary hypertension of the newborn (PPHN), were found to have CHD (transposition: 3; total anomalous pulmonary venous connection: 3; left heart obstructive lesions: 2). Mortality in this group was 50%, compared with 11% for correctly identified CHD patients (odds ratio 8.2, 95% CI 1.92, 35.4, p<0.01). For all neonates with CHD, the risk of death was increased by the presence of cardiovascular collapse and end-organ dysfunction at presentation to the ICU (p<0.01 for both). CONCLUSION: Neonates with CHD may present as severe "PPHN" via the ECMO service. Poor outcome in these patients relates to the high incidence of cardiovascular collapse and end-organ dysfunction. Early echocardiography is recommended for neonates with presumed PPHN. Neonatal ECMO support should be based in centres with cardiac surgical services.     

Severe respiratory syncytial virus bronchiolitis in children: from short mechanical ventilation to extracorporeal membrane oxygenation

The objective of this study was to describe the characteristics of children who required mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) support for respiratory syncytial virus (RSV) bronchiolitis, and to identify risk factors associated with disease severity assessed by duration of MV, mortality and need for ECMO. Ventilated children under 1 year of age admitted for bronchiolitis were retrospectively studied over the 8-year period 1996–2003. The study population included 151 children. Of these, 38.4% were born prematurely and 8.6% had bronchopulmonary dysplasia (BPD). The mean age at initiation of MV was 61 days (±63 days). Infants were ventilated for a mean of 7.8 days (±7.5 days). Multivariate analysis revealed that prolonged duration of MV (>6 days, median value) was significantly associated with low gestational age ( P =0.02 for the group <32 weeks), requirement of neonatal oxygen supplementation ( P =0.03), BPD ( P =0.02) and positive tracheal aspiration culture ( P =0.004), in particular for Haemophilus influenzae ( P =0.03). Fourteen infants required ECMO with a mean period of MV before ECMO of 3.9 days (±4.5 days). Amongst these infants, the frequency of BPD was significantly higher as compared with the others ( P =0.001). Four infants died (survival rate 71.4%). The mean duration of ECMO for survivors was 12.1 days (±3.3 days). Conclusion:The data suggest that gestational age, requirement of neonatal oxygen supplementation, bronchopulmonary dysplasia and tracheal colonisation with Haemophilus influenzae are correlated with prolonged mechanical ventilation in children with bronchiolitis. Only bronchopulmonary dysplasia was associated with a need for extracorporeal membrane oxygenation that may provide lifesaving support in infants refractory to conventional management.     

A meta-analysis of outcomes after open and laparoscopic Nissen��s fundoplication for gastro-oesophageal reflux disease in children

The objective of this study is to meta-analyse the published literature comparing outcomes after open (ONF) versus laparoscopic Nissen fundoplication (LNF) for gastro-oesophageal reflux disease in children. Electronic databases were searched from January 1993 to October 2009. A systematic review was performed to obtain a summative outcome. Six comparative studies were analysed. There were 466 patients in the laparoscopic group and 255 in the open group. There was no significant difference in operative time between LNF compared with ONF (p = 0.35). Children stayed in hospital for less time after undergoing LNF compared with ONF [random effects model: SMD = 0.93, 95% CI (0.41, 1.44), z = 3.53, p < 0.01]. Children feed earlier after LNF [random effects model: SMD = 4.13, 95% CI (1.00, 7.27), z = 2.58, p < 0.001] and had less morbidity [fixed effects model: RR = 3.22, 95% CI (1.98, 5.25), z = 4.71, p < 0.01; random effects model: RR = 2.90, 95% CI (1.49, 5.66), z = 3.12, p < 0.01]. No difference in recurrence at 12 months was highlighted (p = 0.29). In conclusion, the laparoscopic Nissen’s fundoplication in children may be considered a safe and effective alternative to open surgery; however, careful case selection is required.     

Factors Related to Successful Transcatheter Closure of Atrial Septal Defects Using the Amplatzer Septal Occluder

The Amplatzer septal occluder (ASO) is used for transcatheter closure of atrial septal defects (ASDs). This study aimed to determine the factors influencing successful closure with the ASO. A retrospective analysis of 69 patients who underwent transcatheter ASD occlusion between 2003 and 2007 was performed. The ASO was successfully implanted during 67 (97%) of 69 procedures. A major adverse event occurred for 6 patients (9%), and 13 patients (19%) experienced a minor adverse event. The outcome for 53 cases (77%) was a composite clinical success. Patient age (p = 0.191) and consultant experience (p = 0.270) were not important factors in successful ASD occlusion. However, patient weight (p = 0.031), diameter of the defect (p = 0.030), device size (p = 0.044), aortic rim size (p = 0.002), and device/defect ratio (p < 0.001) all were significant factors. Complications were significantly more likely for patients whose device/defect ratio was <1.125 (loose) or ≥1.333 (tight) (p < 0.001). The device/defect ratio may provide a clinically useful tool with the potential to predict patients likely to experience an adverse event as a result of transcatheter ASD occlusion. A larger sample would enable refinement of the device/defect ratio and provide a more robust prediction of success.     

The Impact of Prenatal Diagnosis of Complex Congenital Heart Disease on Neonatal Outcomes

Prenatal diagnosis of congenital heart disease (CHD) is increasingly common. However, the current impact of prenatal diagnosis on neonatal outcomes is unclear. Between January 2004 and January 2008, a retrospective chart review of infants who underwent surgical repair of CHD before discharge at our institution was conducted. Obstetric and perioperative variables were recorded. Of 439 neonates, 294 (67%) were diagnosed prenatally (PREdx). Infants with PREdx had a lower mean birth weight (3.0 ± 0.6 vs. 3.1 ± 0.6 kg, p = 0.002) and gestational age (37.9 ± 2.1 vs. 38.6 ± 2.4 wk, p < 0.001) than those with postnatal diagnosis (POSTdx). Severe lesions were more likely to be PREdx: Neonates with single-ventricle (SV) physiology (n = 130 patients [31.2%]) had increased odds of PREdx (n = 113/130, odds ratio [OR] 4.7; 95% confidence interval [CI] 2.7–8.2, p < 0.001). PREdx was associated with decreased preoperative intubation (OR 0.62; 95% CI 0.42–0.95, p = 0.033), administration of antibiotics (OR 0.23; 95% CI 0.15–0.36, p < 0.001), cardiac catheterization (OR 0.54; 95% CI 0.34–0.85, p = 0.01), and emergency surgery (OR 0.18; 95% CI 0.06–0.5, p < 0.001) compared with POSTdx infants. There was no difference in APGAR scores, preoperative pH, day of life of surgery, operative complications, hospital length of stay, or overall mortality in the PREdx versus POSTdx groups, even when controlling for lesion severity. PREdx was not independently associated with neonatal mortality, despite having included more severe cardiac lesions. PREdx was significantly associated with decreased neonatal morbidity in terms of decreased use of preoperative ventilator, administration of antibiotics, cardiac catheterization, and emergency surgery.     

Nitric oxide in neonatal transposition of the great arteries

Three newborn infants with transposition of the great arteries (TGA) and intact ventricular septum (IVS) developed postnatal persistent pulmonary hypertension of the newborn (PPHN) and were successfully treated with inhaled nitric oxide (iNO). Intervention with balloon atrial septostomy (BAS) was performed in two of the infants before the iNO treatment, but they continued to be severely hypoxic with metabolic acidosis. However, the iNO immediately improved oxygenation and the clinical condition. The third neonate had a moderately large atrial communication and echocardiographic signs of PPHN. He received iNO before BAS with dramatic clinical improvement, which therefore postponed BAS.

Conclusion: Early diagnosis of PPHN and treatment with iNO may improve final outcome in neonates with TGA and IVS. In the presence of moderately large atrial communication and PPHN, treatment with iNO might be considered before BAS.     

The use of F-arginine and phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide

A full-term, female neonate developed acute hypoxemic respiratory failure complicated by persistent pulmonary hypertension of the newborn (PPHN), and responded to high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO). Discontinuation of iNO was attempted three times and was followed by severe desaturation due to right-to-left shunt through the patent ductus arteriosus and patent foramen ovale. As a result of iNO dependency state and rebound pulmonary hypertension, the neonate was maintained on iNO therapy for dipyridamole alone was unsuccessful. However, successful discontinuation of iNO therapy was achieved by combination of L-Arginine and dipyridamole. Exogeous NO may lead to down regulation of endogenous NO production, and further lead to rapid hydrolization of cyclic guanosine 3′, 5′ monophosphate (cGMP), the smooth muscle relaxant, by the enzyme phosphodiesterase. Moreover L-Arginine, the precursor for the formation of endogenous NO, has been found to be deficient in neonates with PPHN,^1,2 so we speculated that by inhibiting phosphodiesterase and administrating L-Arginine smooth muscle relaxation occurred, and consequent weaning from iNO was achieved.     

Vasodilator Testing with Nitric Oxide and/or Oxygen in Pediatric Pulmonary Hypertension

The objective of this study was to determine whether a combination of inhaled nitric oxide (iNO) and O₂ is more effective than 100% O₂ or iNO alone for acute vasodilator testing in children. An open, prospective, randomized, controlled trial was conducted at 16 centers. Subjects were children 4 weeks to 18 years of age with pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) undergoing right heart catheterization for acute vasodilator testing. All patients were tested with each of three agents (80 ppm iNO, 100% O₂, combination of 80 ppm iNO/100% O₂) in three 10-min treatment periods, and hemodynamic measurements obtained. Primary outcome measures were percentages of acute responders with O₂ alone vs. iNO/O₂ and iNO alone vs. iNO/O₂. More patients on the combination were acute responders compared with O₂ or iNO alone (26% vs. 14%, P = 0.019, and 27% vs. 24%, P = 0.602, respectively). Changes in PVR index and mean pulmonary arterial pressure vs. baseline were greater with iNO/O₂ vs. either O₂ or iNO alone (P < 0.001). Survival at 1-year follow-up included (1) 90.9% of acute responders to the combination, compared with 77.8% of nonresponders to the combination, and (2) 85.7% of acute responders to O₂ alone, compared with 80.6% of nonresponders to O₂. Key conclusions are as follows. In children with PH and increased PVR, more acute responders were identified with the iNO/O₂ combination vs. O₂ alone. While there was no significant difference in acute responder rate with iNO alone vs. iNO/O₂, the combination improved pulmonary hemodynamics acutely better than iNO alone. One-year survival data show similar rates between the iNO/O₂ and the O₂ alone groups; however, the combination may be more effective than O₂ alone in discriminating survivors versus nonsurvivors at long-term follow-up.     

Age-Related Acceleration of Endothelial Dysfunction and Subclinical Atherosclerosis in Subjects with Coronary Artery Lesions After Kawasaki Disease

The objective of this study was to test the hypothesis that accelerated endothelial dysfunction and the development of premature atherosclerosis are associated with age in subjects with coronary artery lesions after Kawasaki disease (KD). A case-control study was performed at a university hospital that included 35 post-KD subjects across a wide age range (range, 8–42 years) without traditional cardiovascular risk factors and 35 age- and sex-matched healthy control subjects (Cont). Flow-mediated dilatation (FMD) of the brachial artery-induced by reactive hyperemia, intima media thickness (IMT), and elastic modulus (Ep) of the common carotid artery were compared between KD and Cont subjects assessed against age. KD subjects had slightly higher levels of body mass index, lipid profile, and HbA1c than Cont subjects, but the differences were not significant. The mean IMT (p < 0.001), age-adjusted percentage normal IMT (%N IMT; p < 0.0001), and Ep (p < 0.001) were significantly higher in KD than Cont subjects, and the peak FMD% (p < 0.01) was significantly lower in KD than Cont subjects. There were significant correlations between FMD% and age (r = −0.51 p < 0.0001), IMT and age (r = 0.68, p < 0.001), and Ep and age (r = 0.58, p < 0.01) in KD but not Cont subjects. When the difference in FMD% between KD and matched Cont subjects (ΔFMD%) was plotted against age, no significant relationship was found, although significant correlations between ΔIMT and age (r = 0.52, p < 0.01) as well as between ΔEp and age (r = 0.46, p < 0.05) were observed. When we defined values that were +2.0 SD over the mean control values (i.e., %N IMT ≥ 120% and/or Ep ≥ 50 kPa) as markers of subclinical atherosclerosis, 15 subjects met the criteria. Subjects over the age of 22 years were more likely to have (OR = 16.54, p = 0.0001) subclinical atherosclerosis in this cohort. Our results suggest that endothelial dysfunction and the development of premature atherosclerosis were accelerated in adult post-KD compared to Cont subjects.     

Echocardiographic Evaluation of Children With Systemic Ventricular Dysfunction Treated With Carvedilol

Echocardiography is used to measure the therapeutic effectiveness of heart failure therapy in adults and children. The purposes of this study were (1) to assess baseline echocardiographic predictors of clinical outcome, (2) to investigate changes in echocardiographic parameters, and (3) to compare these echocardiographic changes with changes in plasma levels of b-type natriuretic peptide (BNP) in a population of children with systemic ventricular dysfunction and symptomatic heart failure treated with carvedilol or placebo. All available baseline and 6-month echocardiograms from Pediatric Carvedilol Trial (PCT) participants (carvedilol n = 161; placebo n = 55) were reviewed. Systolic and diastolic sphericity index (SI; n = 110), TEI index (n = 145), and systemic ventricular dP/dt (n = 70) were measured. The PCT composite definition of clinical outcome (i.e., worsened, improved, or unchanged) was used. For all patients, baseline TEI index was a predictor of worsened outcome. Only children treated with carvedilol showed a significant decrease in systolic SI (P ≤ 0.0001), diastolic SI (P ≤ 0.0001), and TEI index (P = 0.02). An inverse correlation between changes in BNP and changes in dP/dt (r = –0.45, P = 0.04) was found only in the carvedilol group. In conclusion, TEI index predicted outcome in children with systemic ventricular dysfunction and heart failure. Carvedilol may have a beneficial effect on reversal of left ventricular remodeling and global ventricular function in pediatric heart failure.     

Benign Outcome of Pulmonary Hypertension in Neonates With a Restrictive Patent Foramen Ovale Versus Result for Neonates With an Unrestrictive Patent Foramen Ovale

Premature closure or restriction of foramen ovale (FO) is a rare but known entity. FO diameter <2 mm and Doppler velocity >120 cm/s, diameter <3 mm with Doppler velocity measured gradient >5 mmHg have all being used by various authors to describe this entity. Some neonates with restrictive FO have been noted to have severe pulmonary hypertension with no clinical signs or symptoms and with spontaneous resolution without any intervention. Seven consecutive neonates were indentified in the database between 01/01/2003 and 06/30/2010 with diagnosis of restrictive PFO (diameter <2 mm) with structurally normal heart and their initial and follow-up echocardiogram as well as hospital medical records were reviewed. As a control, seven neonates with diagnosis of pulmonary hypertension and respiratory distress syndrome or meconium aspiration syndrome were randomly selected. Eighty-six percent of the patients in the control group were symptomatic and required treatment as compared to 14% in the restrictive FO group (p = 0.03). Further, the fall in the peak instantaneous pulmonary artery pressure on follow-up echocardiogram was greater in the restrictive FO group compared with the non-restrictive group (p = 0.03). Patients with pulmonary hypertension and a restrictive FO with no other associated congenital heart disease and/or lung pathology behave differently when compared to neonates with non-restrictive FO and pulmonary hypertension with associated lung disease. They seldom manifest symptoms requiring intervention and tend to show a faster drop in their pulmonary artery pressure toward the normal.     

Aortic Dimensions in Girls and Young Women with Turner Syndrome: A Magnetic Resonance Imaging Study

This study aimed to determine the dimensions of the thoracic aorta and the predictors of aortic dimensions in girls and young women with Turner syndrome (TS). A cross-sectional study was performed at a secondary care center. The study compared 41 TS patients with 50 healthy age-matched control subjects. The mean age of the patients was 17 ± 3.3 years. Magnetic resonance imaging was performed for all the patients. The thoracic aortic diameters of the patients were measured at nine positions. Adjustment for body surface area (BSA) was performed. The outcome for the patients was measured in terms of absolute and BSA-adjusted aortic dilation. In TS, both the absolute and the BSA-adjusted mean aortic diameters were smaller than or comparable with those of the control subjects. However, individual aortic dilation at one to four positions was found in four TS patients according to the uncorrected data and in five TS patients after BSA-adjustment. The aortic diameters correlated with height, weight, body mass index (BMI), and BSA at all positions (R = 0.34–0.60; all p < 0.04). The diameters of the aortic arch and the descending aorta correlated with a history of aortic coarctation (R = 0.35–0.52; p < 0.03). The presence of bicuspid aortic valves correlated at the descending part of the aorta (R = 0.38; p < 0.03). The mean thoracic aortic dimensions were not enlarged in girls or young TS patients. The BSA predicted aortic size at all positions. The prevalence of aortic dilation and aneurysm was lower in this population of girls and younger women with TS than in older TS populations.