Prospective Single-Arm Protocol of Carvedilol in Children with Ventricular Dysfunction

The objective of this study was to evaluate the safety and efficacy of carvedilol in pediatric patients with stable moderate heart failure. We performed a single-arm prospective drug trial at three academic medical centers and the results were compared to historical controls. Patients were 3 months to 17 years old with an ejection fraction <40% in the systemic ventricle for at least 3 months on maximal medical therapy including ACE inhibitors. Treated patients were started on 0.1 mg/kg/day and uptitrated to 0.8 mg/kg/day or the maximal tolerated dose. Echocardiographic parameters of function were prospectively measured at entry and at 6 months. Two composite endpoints were recorded: severe decline in status and significant clinical change. Adverse events were reviewed by a safety committee. Data were also collected from untreated controls with dilated cardiomyopathy meeting entry criteria, assessed over a similar time frame. Twenty patients [12 dilated cardiomyopathy (DCM) and 8 congenital] with a median age of 8.4 years (range, 8 months to 17.8 years) were treated with carvedilol. Three patients discontinued the drug during the study. At entry, there was no statistical difference in age, weight, or ejection fraction between the treated group and controls. The ejection fraction of the treated DCM group improved significantly from entry to 6 months (median, 31 to 40%, p = 0.04), with no significant change in ejection fraction in the control group [median, 29 to 27%, p = not significant (NS)]. The median increase in ejection fraction was larger for the treated DCM group than for the untreated DCM controls (7 vs 0%, p = 0.05). By Kaplan–Meier analysis, time to death or transplant tended to be longer in treated patients (p = 0.07). The difference in the proportion of patients with severe decline in status or significant clinical change in the treated group was not significant compared to the controls (5 vs 12%, p = NS). We conclude that in this prospective protocol of pediatric patients, the use of adjunct carvedilol in the DCM group improved ejection fraction compared to untreated controls and trended toward delaying time to transplant or death.     

Electrocardiographic Strain Pattern in Children With Left Ventricular Hypertrophy: A Marker of Ventricular Dysfunction

The objective of this study was to assess the relation between strain pattern on electrocardiogram (ECG-strain) and echocardiographic indices of left ventricular (LV) structure and function in children with LV hypertrophy (LVH). ECG-strain is a marker of LVH and is associated with adverse cardiovascular prognosis in adults. The significance of ECG-strain and its relation to LV structure and function has not been studied in children. We retrospectively analyzed electrocardiograms (ECGs) and echocardiograms of 101 children enrolled in this study. Subjects were divided into three groups: group I (n = 21) comprised children with LVH confirmed by echocardiography (LVH_echo) with ECG-strain pattern; group II (n = 54) comprised children with LVH_echo without ECG-strain pattern; and group III (n = 26) comprised children without LVH (control group). ECG-strain was defined as a down-sloping convex ST-segment depression (≥0.1 mV) with an inverted asymmetrical T-wave opposite to the QRS axis in leads V5 and/or V6. LV structure and function was measured using conventional and tissue Doppler echocardiography. ECG-strain was associated with greater interventricular septal thickness, posterior wall thickness, and LV mass index (LVMI) compared with those without ECG-strain (P < 0.0001 for each variable). Concentric LVH was more common in those with ECG-strain (16 of 21 vs. 9 of 54 patients; P = < 0.0001). ECG-strain was associated with systolic, diastolic, and combined systolic–diastolic dysfunction in children with LVH_echo. Among children with LVH, ECG-strain is associated with higher LVMI, concentric pattern of LVH, and LV systolic and diastolic dysfunction. Whether this has similar adverse prognostic implications as it does in adults remains to be determined.     

Left Ventricular Diastolic Dysfunction in Children and Young Adults with Marfan Syndrome

Adults with Marfan syndrome (MFS) demonstrate abnormal aortic elastic properties manifest by decreased aortic distensibility and increased aortic stiffness. Left ventricular (LV) diastolic dysfunction has been reported in adults with MFS. The objective of this study was to assess the frequency of LV diastolic dysfunction in a group of children and young adults with MFS and to determine whether diastolic dysfunction is associated with hemodynamic alterations of the aorta. Review of echocardiographic findings in 40 patients with MFS was performed to assess LV size, systolic function, isovolumic relaxation time (IVRT), mitral inflow velocities, deceleration time (DT) of mitral E wave, and aortic root dimension. No patient had significant valvar disease or was on any cardiac medication at the time of study. A group of 40 age and sex-matched healthy subjects undergoing echocardiography served as controls. Significant differences in LV diastolic function were found between MFS patients and controls. MFS patients had prolonged DT and IVRT and decreased mitral E/A ratio, suggesting impaired LV relaxation. No relationship between aortic root dimension and diastolic performance was identified. Left ventricular diastolic dysfunction may be an early marker of myocardial involvement in young MFS patients occurring independently of aortic root dilatation.     

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.     

Reverse Ventricular Remodeling and Improved Ventricular Compliance After Heart Transplantation in Infants and Young Children

After heart transplantation (HT) in infants and young children, environmental and intrinsic factors may lead to changes in the geometry and compliance of the donor heart. Serial demographic, clinical, hemodynamic, and echocardiographic data were obtained from HT recipients younger than 4 years of age. Echocardiographic chamber measurement z-scores were compared using recipient body surface area from the time of HT to 1 week, 3 months, and last follow-up visit. Left ventricular end-diastolic volume (LVEDV) z-scores were correlated with pulmonary capillary wedge pressure (PCWP) at each time point. Heart transplantation was performed for 13 children between March 2009 and December 2012, 9 of whom (69 %) were boys. The median age at HT was 8 months (range, 4–43 months), and the mean follow-up period was 13 ± 7 months. Left ventricular end-diastolic dimension z-scores decreased significantly (p = 0.03) between HT and 1 week, then increased from 1 week to 3 and 12 months. (?1.32 ± 1.7, ?0.71 ± 1.8, 0.41 ± 2.1, 0.79 ± 2.3, respectively). A positive relationship (R ² = 0.48) between the LVEDV z-score and PCPW was present at the last follow-up visit. For infants and young children, the allograft demonstrates appropriate growth by 1 year after HT. Left ventricular compliance improves over time.     

儿童脑积水脑室腹腔分流术后感染的临床分析

目的探讨儿童脑积水脑室腹腔分流术后感染的防治。方法回顾性分析儿童脑积水行脑室腹腔分流术后感染的14例患儿临床资料,其中11例为首次分流术后并发感染,2例为分流管修改术后出现感染,1例为腹部手术后出现感染。结果14例中死亡6例,其中5例死于与分流感染有关的并发症。另8例经治疗痊愈,经随访2～10年均健康生存。结论预防分流感染相当重要,术前应行预防性抗感染治疗,术后感染确诊应及时足量静脉输入有效的抗生素,分流术后感染等病例再次分流宜慎重。     

心脏电生理变化早期检测蒽环类药物对血液/肿瘤病患儿的心脏毒性

目的 评价通过检测白血病、实体瘤患儿心脏电生理活动变化,早期发现蒽环类药物(ANT)对血液/肿瘤病患儿心脏毒性的可行性.方法 选择2003年8月-2009年3月在本院接受ANT治疗、疗程全部结束并达完全缓解的白血病、实体肿瘤患儿65例.男38例,女27例;年龄1～16(6±4)岁;发病年龄5个月～14岁[(4.0±4.5)岁].ANT疗程结束后随访时间为1～49(20.88±13.23)个月;ANT累积剂量为25～350(125.82±74.85) mg·m-2.分别检测患儿QTc间期及常规超声(2-DE),并与25例健康体检儿童(健康对照组)比较.患儿心率变异(HRV)与本院正常参考值比较.结果 患儿均无心功能不全临床表现.与健康对照组比较,常规2-DE指标无明显变化.QTc间期:65例患儿化疗前QTc均在正常范围,化疗后44例患儿QTc较化疗前延长,3例延长超过正常范围(＞440 ms).化疗后QTc较化疗前及健康对照组均明显延长.QTc延长与ANT剂量及随访时间无相关性.45例患儿与本院HRV正常参考值比较,24 h内全部正常窦性心动周期(N-N)的标准差、24 h全程相邻N-N间期之差的均方根值、24 h内相邻N-N间期差值＞50 ms个数占所有N-N间期个数的百分数等时域指标及极低频率、低频、高频等频域指标均明显下降(Pa＜0.05).ANT化疗后随访时间最长者及联合接受长春新碱剂量最大者HRV受累更明显.结论 ANT累积剂量25～350(125.82±74.85) mg·m-2,随访1～49(20.88±13.23)个月的患儿发生恶性心脏事件风险不大,但患儿心室复极化及HRV已受影响,属危险人群,需长期监测;相比常规2-DE指标,QTc、HRV可更敏感地反映亚临床心脏毒性;ANT化疗及联合大剂量VCR可加重化疗后心脏自主神经功能受损.     

Academic Proficiency in Children After Early Congenital Heart Disease Surgery

Children with early surgery for congenital heart disease (CHD) are known to have impaired neurodevelopment; their performance on school-age achievement tests and their need for special education remains largely unexplored. The study aimed to determine predictors of academic achievement at school age and placement in special education services among early CHD surgery survivors. Children with CHD surgery at <1 year of age from January 1, 1998 to December 31, 2003, at the Arkansas Children’s Hospital were identified. Out-of-state births and infants with known genetic and/or neurologic conditions were excluded. Infants were matched to an Arkansas Department of Education database containing standardized assessments at early school age and special-education codes. Predictors for achieving proficiency in literacy and mathematics and the receipt of special education were determined. Two hundred fifty-six children who attended Arkansas public schools and who had surgery as infants were included; 77.7 % had either school-age achievement-test scores or special-education codes of mental retardation or multiple disabilities. Scores on achievement tests for these children were 7–13 % lower than those of Arkansas students (p < 0.01). They had an eightfold increase in receipt of special education due to multiple disabilities [odds ratio (OR) 10.66, 95 % confidence interval (CI) 4.23–22.35] or mental retardation (OR 4.96, 95 % CI 2.6–8.64). Surgery after the neonatal period was associated with decreased literacy proficiency, and cardiopulmonary bypass during the first surgery was associated with decreased mathematics proficiency. Children who had early CHD surgery were less proficient on standardized school assessments, and many received special education. This is concerning because achievement-test scores at school age are “real-world” predictors of long-term outcomes.     

小儿室间隔缺损术后残余漏

８例小儿室间隔缺损修补术后残余漏再次手术病例分析：残余漏表现为５例术后残留心前区Ⅲ级以上收缩期杂音，７例血红蛋白尿，２例右心衰，８例超声心动图（ＵＣＧ）证实心室水平残余左向右分流。均于术后２～１１２天行残余漏修补。术中见残余漏原因为不同部位缝针处组织撕裂６例，修补不全２例。８例均经带垫片褥式缝合加固，７例痊愈，１例再次发生残余漏。本文对残余漏特点、诊断、手术适应证及时机进行了讨论。     

化疗对肝功能异常的噬血细胞性淋巴组织细胞增生症的有效性及安全性观察

目的初步评价化疗对并肝功能异常的噬血细胞性淋巴组织细胞增生症(HLH)患儿的有效性及安全性。方法选取对2004年3月-2008年4月收治的非肿瘤相关HLH患儿,参照由地塞米松、依托泊苷、环孢素组成的HLH-04化疗方案指南,在化疗后第8周对疗效进行评估,并在治疗前、治疗后2周、治疗后8周末监测血清ALT、血清清蛋白(Alb)、血浆纤维蛋白原(Fib)等指标变化。结果共60例HLH患儿在接受免疫化疗前并肝功能异常,其中ALT增高47例,Alb降低58例,Fib降低38例。病毒感染相关42例(70%),真菌感染相关1例(1.7%),不明原因17例(28.3%)。60例患儿中55例在诱导治疗4周中临床有效,15例患儿放弃治疗,45例患儿按统一方案完成了8周诱导治疗(其中42例无活动性病变,3例存在活动性病变),该45例患儿治疗后2周、8周,ALT、Alb、Fib监测指标均明显改善,与治疗前比较,组间差异均有统计学意义(Pa<0.01)。结论HLH-04化疗方案治疗HLH临床疗效显著,同时对化疗前肝功能异常患儿同样具有较好的安全性。病初肝功能异常并非免疫化疗的禁忌证,在监测肝功能的基础上应尽可能按时足量应用。     

Outcomes in Patients with Persistent Ventricular Dysfunction After Stage I Palliation for Hypoplastic Left Heart Syndrome

We sought to describe the clinical course for patients with hypoplastic left heart syndrome and persistent ventricular dysfunction and identify risk factors for death or transplantation before stage II palliation. 138 children undergoing stage I palliation from 2004 to 2011 were reviewed. Twenty-two (16 %) patients (seven Hybrid, 15 Norwood) with two consecutive echocardiograms reporting at least moderate dysfunction were included and compared to case-matched controls. Eleven of the 22 patients with dysfunction (50 %) underwent stage II, seven (32 %) were transplanted, and four (18 %) died prior to stage II. Of the patients who survived to hospital discharge (n = 17) following stage 1, 14 (82 %) required readmission for heart failure (HF) compared to only two (10 %) for controls (p < 0.001). Among patients with ventricular dysfunction, there was an increased use of ACE inhibitors or beta-blockers (82 vs. 25 %; p = 0.001), inotropes (71 vs. 15 %; p = 0.001), ventilation (58 vs. 10 %; p = 0.001), and ECMO (29 vs. 0 %; p = 0.014) for HF management post-discharge when compared to controls. There was a lower heart transplant-free survival at 7 months in patients with dysfunction compared to controls (50.6 vs. 90.9 %; p = 0.040). ECMO support (p = 0.001) and duration of inotropic support (p = 0.04) were significantly associated with death or transplantation before stage II palliation. Patients with ventricular dysfunction received more HF management and related admissions. Longer inotropic support should prompt discussion regarding alternative treatment strategies given its association with death or transplant.     

Right Ventricular Dysfunction and B-Type Natriuretic Peptide in Asymptomatic Patients After Repair for Tetralogy of Fallot

Early detection of right ventricular (RV) dysfunction is essential in the assessment of patients with repaired tetralogy of Fallot (TOF). This study aimed to assess latent RV dysfunction in asymptomatic patients with TOF and to determine the predictive value of B-type natriuretic peptide (BNP). Pressure–volume loops were recorded for 16 young patients (New York Heart Association class 1 or Ross class 0; median age, 14.2 years) using the conductance catheter technique. All the patients had RV dilation secondary to pulmonary regurgitation after surgical repair of TOF. Indexes of RV function were derived at baseline level and during dobutamine infusion. Contractility was calculated by the slope of the end-systolic pressure–volume relation (ESPVR). An increase in ESPVR during dobutamine infusion was considered to indicate contractile reserve as a marker for latent RV dysfunction. The median ESPVR significantly increased from 0.32 mmHg/ml (0.13–0.72 mmHg/ml) at baseline to 0.57 mmHg/ml (0.24–1.55 mmHg/ml) during dobutamine infusion (p = 0.005). However, for five patients, no relevant increase in contractility was found, indicating impaired RV contractile reserve. There was only a weak inverse correlation between impaired contractile reserve and BNP (r = −0.28). Even asymptomatic patients with only a mildly enlarged right ventricle can have impaired RV function. Early RV dysfunction cannot be predicted accurately with BNP.     

Brain Natriuretic Peptide as a Hormonal Marker of Ventricular Diastolic Dysfunction in Children with Kawasaki Disease

Although an increased level of serum brain natriuretic peptide (BNP) has been reported in children in the acute phase of Kawasaki disease (KD), no precise relation was documented between the serum BNP level and left ventricular (LV) systolic function. We hypothesized that the increased BNP levels may be explained by diastolic abnormalities in those with KD. We prospectively studied 25 patients in the acute phase of KD. Patients with abnormal systolic function were excluded. Pediatric cardiologists making the assessment of LV diastolic function were blinded to the BNP levels. Doppler interrogation was applied to measure LV inflow velocities, which were transformed to z scores using control measurements obtained from 83 healthy subjects. In the patients, the BNP levels ranged from 2.0 to 450.0 pg/ml, with a mean of 54.0 ± 102.8 pg/ml. Six patients with abnormal velocities (> 2 SD in z score) showed significantly higher levels of BNP (152 ± 173 pg/ml) than those in the remaining patients (p < 0.01). The BNP levels correlated positively with diastolic atrial velocity in z score (r = 0.51, p < 0.05), and negatively with diastolic early velocity to atrial velocity ratio in z score (r = -0.75, p < 0.01). This study suggests that LV diastolic dysfunction may occur in some children in the acute phase of KD, causing an increased level of BNP.     

Severe Left Ventricular Dysfunction and Arrhythmias as Complications of Gram-Positive Sepsis: Rapid Recovery in Children

Severe left ventricular dilatation and dysfunction in children may be associated with poor outcome in as many as 45% of cases. The prognosis for children with poor left ventricular function or arrhythmias associated with septic shock may be better, however, this has been inadequately studied. We report the favorable outcome of three children who presented with Gram-positive sepsis and significant cardiovascular compromise—two with severely dilated, poorly contractile left ventricle, and one with mild left ventricular dysfunction and incessant, malignant, and rapid atrial and ventricular arrhythmias. Our experience with these patients shows that complete and rapid resolution of these complications may be achieved with aggressive therapy.     

Early Subclinical Left-Ventricular Dysfunction in Obese Nonhypertensive Children: A Tissue Doppler Imaging Study

A direct effect of obesity on myocardial function has not been not well established. Our aim was to investigate the effect of body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA–IR) on left-ventricular (LV) myocardial function in normotensive overweight and obese children by tissue Doppler imaging (TDI). We calculated the mitral annular displacement index (DI) and myocardial performance index (MPI) using TDI indices of systolic and diastolic LV function. In this hospital-based, prospective cross-sectional study, we studied 60 obese (mean age 13.2 ± 2.0 years) and 50 normal children. Subjects were divided into three groups: group 1 (BMI < 25, n = 50, control), group 2 (BMI 25–29.9 kg/m², n = 30, overweight), and group 3 (BMI ≥ 30 kg/m², n = 30, morbidly obese). Standard echocardiography showed increased LV diameters and LV mass/index and preserved ejection fraction in obese children. By TDI, LV systolic and diastolic function showed that peak late myocardial velocity (Em = 15.4 ± 2 cm/s), peak early myocardial velocity (Am = 8.7 ± 1.3 cm/s), Em/Am ratio (1.8 ± 0.3), isovolumetric relaxation time (IVRT = 59.2 ± 8.2 ms), MPI (0.39 ± 0.03), and DI (25.5 ± 3.2 %) of the lateral mitral annulus in the obese subgroups were significantly different from those of control subjects (18.2 ± 1.2 cm/sn, 6.9 ± 0.6 cm/sn, 2.6 ± 0.2, 51.2 ± 9.6 ms, 0.34 ± 0.03, and 33.13 ± 5.0 %, respectively; p < 0.001). These structural and functional abnormalities were significantly related to BMI. There were positive correlations between HOMA–IR, septal MPI, and LV mass. DI and MPI data indicated impaired subclinical LV function in all grades of isolated obesity at a preclinical stage. Insulin resistance and BMI correlated significantly with indices of LV function.