Tak-cheung Yung

Increased high sensitivity C reactive protein concentrations and increased arterial stiffness in children with a history of Kawasaki disease

Objectives: To test the hypothesis that low grade inflammation persists after the acute phase and affects arterial stiffness in children with a history of Kawasaki disease. Design and patients: A cohort of 106 children was studied, which comprised 43 patients with Kawasaki disease with coronary aneurysms (group I), 28 patients with Kawasaki disease with normal coronary arteries (group II), and 35 healthy age matched children (group III). Their systemic blood pressure, fasting cholesterol concentrations, serum high sensitivity C reactive protein (hs-CRP) concentrations, and carotid artery stiffness index were compared. Significant determinants of serum hs-CRP concentration and carotid artery stiffness were identified and the relation between hs-CRP concentration and arterial stiffness was investigated. Setting: Tertiary paediatric cardiac centre. Results: Serum hs-CRP concentration of group I patients (median 0.39 mg/l, interquartile range 0.28–0.65 mg/l) was significantly greater than that of group II (median 0.24 mg/l, interquartile range 0.17–0.29 mg/l, p < 0.001) and of group III patients (median 0.25 mg/l, interquartile range 0.18–0.40 mg/l, p < 0.01). Likewise, carotid artery stiffness index of group I patients (mean (SD) 5.07 (1.11)) was significantly greater than that of group II (4.27 (0.83), p  =  0.002), and of group III patients (4.24 (0.86), p  =  0.001). For the entire cohort, the carotid artery stiffness index correlated positively with log serum hs-CRP concentration (r  =  0.24, p  =  0.013). In multiple linear regression analysis, age (standardised β  =  0.22, p  =  0.02), systolic blood pressure (standardised β  =  0.28, p  =  0.01), log serum hs-CRP concentration (standardised β  =  0.21, p  =  0.017), and patient grouping (standardised β  =  −0.36, p < 0.001) were all independently associated with the carotid artery stiffness index. Conclusions: These findings support the possibility of ongoing low grade inflammation late after the acute phase of Kawasaki disease in patients with coronary aneurysms. Furthermore, this low grade inflammation may have a role in increasing systemic arterial stiffness.

Analysis of indications for surgical closure of subarterial ventricular septal defect without associated aortic cusp prolapse and aortic regurgitation

Subarterial ventricular septal defect (VSD) is relatively common in Orientals. We reviewed the outcome of 214 patients (137 males) who were followed for 8.6 +/- 5.2 years (range 0.1 to 24.3) and addressed the issue regarding the necessity and optimum timing of closing subarterial defects before development of aortic valve deformities. Demographic data, transthoracic and transesophageal echocardiographic findings, cardiac catheterization results, and operative findings were reviewed. Kaplan-Meier actuarial analysis was performed to assess the development of aortic valve complications over time. Seventy-five patients with heart failure and pulmonary hypertension underwent surgical closure of VSD at the age of 2.4 +/- 2.9 years. No patient had aortic cusp prolapse before operation and none developed aortic cusp prolapse or aortic regurgitation (AR) on follow-up. In contrast, of the 139 asymptomatic patients managed conservatively, 102 (73%) developed aortic cusp prolapse, 78% of whom (80 of 102) developed AR. The prevalence of aortic cusp prolapse and AR at 1, 5, 10, and 15 years old was 8%, 30%, 64%, and 83%, and 3%, 24%, 45%, and 64%, respectively. Significant prolapse or AR prompted surgical closure of VSD with (n = 22) or without (n = 26) valvoplasty in 48 of 102 patients (47%). The size of the VSD was significantly larger in patients with heart failure (9.6 +/- 3.3 mm) or aortic cusp prolapse (11.7 +/- 4.1 mm) compared with those without heart failure (4.5 +/- 1.4 mm, p <0.001). All patients with aortic cusp prolapse and all but 1 with heart failure had a defect size of > or =5 mm. In conclusion, subarterial VSD of > or =5 mm should be closed as early as possible to prevent development of aortic cusp prolapse and AR. Asymptomatic patients with small defects <5 mm could be managed conservatively.

Outcome of infants with right atrial isomerism: is prognosis better with normal pulmonary venous drainage?

Objective: To compare the outcome of infants and children who have right atrial isomerism and normal pulmonary venous drainage with those who have anomalous drainage, and to determine factors associated with poor outcome. Design and patients: Retrospective review of management and outcome of 116 infants and children determined to have right atrial isomerism between January 1980 and December 2000. Setting: Tertiary paediatric cardiac centre. Results: The 116 patients presented at a median of one day (range 1 day to 3.7 years) with cyanosis in the majority (96%). No interventions were planned in 31 (27%) patients, all of whom died. The early surgical mortality for pulmonary venous repair was 25% (2 of 8), Fontan procedure 26% (5 of 19), cavopulmonary shunting 7.7% (1 of 13), and systemic pulmonary arterial shunt insertion 1.9% (1 of 53). Late mortality was related to infection (n = 10), sudden death of unknown aetiology (n = 7, 5 with history of arrhythmia), and documented arrhythmia (n = 1). Patients with obstructed anomalous pulmonary venous drainage had the worst survival (p < 0.001). The mean (SEM) survival estimates for those with normal pulmonary venous drainage at 1, 5, 10, and 15 years was 81 (5.3)%, 67 (6.6)%, 60 (7.8)%, and 43 (12)%, respectively, similar to those for patients with non-obstructed anomalous drainage (p = 0.06). Independent risk factors for mortality included pulmonary venous obstruction (relative risk 3.8, p = 0.001) and a single ventricle (relative risk 2.9, p = 0.016). An analysis of only patients with normal pulmonary venous drainage identified no risk factors for mortality. Conclusions: The long term outcome of infants and children with right atrial isomerism in association with a normal pulmonary venous drainage remains unfavourable. Sepsis and sudden death that may potentially be related to cardiac arrhythmia are major causes of late mortality.

Modulating effects of mannose binding lectin genotype on arterial stiffness in children after Kawasaki disease.

Systemic arterial stiffness is increased in patients after Kawasaki disease (KD). Recently, associations between mannose-binding lectin (MBL) gene mutation and coronary complications in infants with KD and atherosclerosis in adults have been reported. We tested the hypothesis that MBL genotype modulates arterial stiffness in children after KD. Seventy-one KD patients (42 with and 29 without coronary aneurysms), aged 9.5 ± 3.7 y, and 41 age-matched controls were studied. We determined and compared their blood pressure, brachioradial arterial stiffness as determined by pulse wave velocity (PWV), fasting total cholesterol, serum MBL level, and MBL genotype. Additionally, the modulating effects of different MBL expression genotypes [high level (HL) versus intermediate or low level (IL/LL)] on arterial stiffness in different groups were assessed. The MBL genotype distributions did not differ between patients and controls (p = 0.41) or between patients with and without coronary aneurysms (p = 0.42). Patients with IL/LL expression genotypes had significantly faster PWV than those with HL expression genotypes (7.93 ± 1.38 m/s versus 6.67 ± 2.28 m/s, p = 0.027). This genotype-modulating effect is more pronounced in patients without (HL 8.86 ± 0.77 m/s versus IL/LL 6.48 ± 2.32 m/s, p = 0.02) than those with (HL 7.50 ± 1.41 m/s versus IL/LL 6.80 ± 2.28 m/s, p = 0.32) coronary aneurysms. Multiple linear regression analysis identified age (β = 0.26, p = 0.012), being a Kawasaki patient (β = 0.22, p = 0.015), and MBL IL/LL genotype subgroup (β = 0.20, p = 0.03) as significant determinants of arterial stiffness in the entire cohort. In conclusion, MBL genotype modulates arterial stiffness, an important cardiovascular risk factor, in children after KD.

Evolution of the management approach for pulmonary atresia with intact ventricular septum

Objective: To review the evolution of the management approach for pulmonary atresia with intact ventricular septum (PAIVS) in the past two decades and to assess its impact on patient outcomes. Design and patients: Retrospective review of the management and outcomes of 94 patients (55 male patients) with PAIVS diagnosed between July 1980 and August 2003. Settings: Tertiary paediatric cardiac centre. Results: Seven patients died before interventions. Of the remaining 87 patients who underwent intervention at a median age of 9 days (from 1 day to 2 years), 12 had right ventricular outflow tract reconstruction (RVOTR), 42 had closed pulmonary valvotomy (CPV), and 15 had laser assisted valvotomy with balloon valvoplasty. A systemic–pulmonary shunt was inserted in 18 patients, six of whom had subsequent RVOTR (n  =  4) or laser assisted valvotomy (n  =  2). Since 1990, catheter intervention accounted for 38% (17 of 45) of the right ventricular outflow procedures. The mean (SEM) freedom from reintervention was 93 (7)%, 71 (12)%, and 57 (13)% after RVOTR, 75 (7)%, 40 (8)%, and 14 (6)% after CPV, and 54 (13)%, 24 (12)%, and 16 (10)% after laser assisted valvotomy at one month, six months, and one year, respectively (RVOTR versus CPV, p < 0.001; RVOTR versus laser assisted valvotomy, p  =  0.001). Low cardiac output syndrome was significantly less common after catheter intervention than after RVOTR (0% v 44%, p  =  0.003) or CPV (0% v 29%, p  =  0.01). The overall mean (SEM) survival was 77 (5)% and 70 (5)% at one and five years, respectively, and the overall mortality was 33% (29 of 87). There were no significant differences in survival between the three groups. Conclusions: Multiple interventions are often required in the treatment algorithm of PAIVS. The shift towards increased use of the transcatheter approach has reduced the occurrence of postprocedural low cardiac output syndrome.

Intraoperative TEE Assessment of Ventricular Septal Defect With Aortic Regurgitation

BACKGROUND It is desirable to repair but not replace the aortic valve in patients with ventricular septal defect and acquired aortic regurgitation. Precise definition of the valvar pathology with monitoring of its repair perioperatively would enhance the surgical management of this condition. METHODS Fourteen consecutive patients (age, 10.6 +/- 6 years; weight 29.7 +/- 5.7 kg) who underwent repair of ventricular septal defect with aortic regurgitation were studied by intraoperative transesophageal echocardiography. The severity of prolapse of each of the individual aortic cusps and its adjacent sinus was assessed and the valvar regurgitation quantified by Doppler-derived regurgitant indices. The echocardiographic and surgical findings were correlated and the preoperative and postoperative echocardiographic data were compared to assess the effectiveness of operation. RESULTS Eight subarterial and six perimembranous defects were located accurately and their sizes (11.8 +/- 3.0 mm) correlated well (r = 0.80) with the surgical measurements. Transesophageal echocardiography detected prolapse of the aortic valve and its sinus in all 14 patients. The severity of the prolapse was severe in 10, moderate in 4, and mild in 5 leaflets. One the basis of these findings, together with the Doppler-derived mean regurgitant indices, exploration of the valve and valvuloplasty were executed appropriately in 12 of 14 patients. In all 14 patients, transesophageal echocardiography after bypass revealed no further cuspal prolapse and significant reduction of the mean regurgitant index (0.55 +/- 0.23 to 0.17 +/- 0.15, p < 0.0001). Residual ventricular septal defect was detected in 5 patients and the only patient with significant shunting who required reexploration was identified correctly. CONCLUSIONS Intraoperative transesophageal echocardiography can assess effectively the surgical repair of ventricular septal defect with aortic regurgitation and provide information that directs and alters surgical plans to the benefit of patients.

Heart rate variability in childhood obstructive sleep apnea.

The identification of patients with obstructive sleep apnea (OSA) is important because of morbidities associated with OSA. A previous adult study demonstrated the use of heart rate variability (HRV) as a tool to identify patients with moderate to severe OSA. Either a reduction in time parameters or an increase in LF/HF ratio was seen at overnight or 24‐hr studies suggestive of increased sympathetic modulation. To study the feasibility of daytime HRV as a screening tool, a short‐term recording of HRV is studied. Since it was shown in adult study that increased normalized LF, decreased normalized HF and increased LF/HF ratio could be detectable during supine rest at daytime awake period, the authors hypothesize that the differences are also detectable in children. Children who underwent sleep polysomnography for suspected OSA were recruited. Subjects were classified OSA if apnea‐hypopnea index (AHI) > 1.5/hr and non‐OSA if AHI ≤ 1.5/hr. Continuous 1‐hr electrocardiographic monitoring was recorded in awake children during the day. Parameters from time domain and frequency domain were analyzed. Seventy‐four male and 17 female snoring subjects were included in this study. Fifty‐one (56%) and 40 (44%) of them were classified as “non‐OSA” and “OSA,” respectively. pNN50, a parameter for parasympathetic modulation, was significantly reduced in the OSA group when compared with the non‐OSA group. Using multiple regression, all time domain variables were shown to be decreased in OSA group. Our results suggest that 1‐hr study of HRV may be a feasible tool in identifying children with OSA. Pediatr Pulmonol. 2011; 46:205–210.

Surgical Validation and Implications for Transcatheter Closure of Quantitative Echocardiographic Evaluation of Atrial Septal Defect

Accurate evaluation of secundum atrial septal defect (ASD) is important for the success of transcatheter closure. The purpose of this study was (1) to describe a quantitative evaluation by transthoracic (TTE) and transesophageal (TEE) echocardiography of the various morphologic features of ASD that might be important for patient selection for transcatheter closure, and (2) to assess the reliability of these 2 methods by surgical findings. Preoperative TTE and TEE were used to evaluate the ASD of 27 children undergoing surgical closure. Measurements included the diameters of ASD and the atrial septal lengths in the transverse and longitudinal axis, and the width of the superior, inferior, anteroinferior, and posterior septal margins. The shape and location of the ASD and the adequacy of the septal margins for anchoring occluding devices were determined. Echocardiographic data were compared with corresponding surgical measurements. No significant difference occurred in the means of all the parameters measured with the 3 methods, except for the transverse ASD diameter (p <0.05). Good agreement occurred between TTE and TEE and surgical data, except for the transverse ASD diameter, transverse atrial septal length, and the posterior septal margin on TTE. Intraclass correlations between TTE and TEE and surgical measurements of all parameters were good, except for the transverse ASD diameter. The accuracy in determining shape and location of the ASD by TTE and TEE were 100%, whereas that for determining the adequacy of septal margins was 98% and 97%, respectively. In conclusion, TTE and TEE are reliable methods for quantitative evaluation of ASD.

Left ventricular noncompaction in children.

OBJECTIVE Left ventricular noncompaction (LVNC) is an uncommon type of cardiomyopathy in children. We sought to determine the clinical presentations and outcomes of children diagnosed to have LVNC. DESIGN The case records of children diagnosed to have LVNC between 1999 and 2007 were reviewed. The diagnosis was based on echocardiographic finding of a thick noncompacted myocardium layer characterized by a trabecular meshwork with deep endomyocardial spaces. RESULTS Ten patients (seven males) were diagnosed to have LVNC at a median age of 2 years (range, 7 days to 12 years). Seven patients had isolated LVNC while three had associated structural congenital heart diseases. The right ventricle was also involved in two patients. Clinical presentations included congestive heart failure in eight patients, asymptomatic heart murmur in one, and syncope with exercise intolerance in one. At presentation, cardiomegaly was found in nine patients, electrocardiographic abnormalities in nine, and impaired LV contraction in six. Eight patients received anti-heart failure medications. Three patients died at a median of 1.5 years after diagnosis, two died suddenly of unknown causes, and one of heart failure. The seven surviving patients were followed up for a median of 2 years (range, 2 months to 3 years). Three patients developed cardiac arrhythmias. The LV function improved in three patients and worsened in one on follow-up. None of the patients developed thromboembolic complications. CONCLUSIONS Left ventricular noncompaction in children is a heterogeneous condition. Long-term follow-up for development of progressive LV dysfunction and cardiac arrhythmias is indicated.

Impact of Right Ventricular Pacing on Three-Dimensional Global Left Ventricular Dyssynchrony in Children and Young Adults With Congenital and Acquired Heart Block Associated With Congenital Heart Disease

The aim of this study was to determine the effect of long-term right ventricular pacing on left ventricular (LV) mechanical dyssynchrony in children and young adults with congenital and acquired heart block. Eighteen patients aged 19 +/- 7 years with congenital heart block (group I), 9 aged 21 +/- 11 years with acquired heart block after congenital heart surgery (group II), and 15 healthy control subjects (group III) were studied. The LV volumes, ejection fractions, and systolic dyssynchrony index (SDI) values, as determined using 3-dimensional echocardiography, were compared among groups. Groups I (6.68 +/- 2.44%) and II (9.43 +/- 4.44%) had significantly greater SDI values than group III (3.88 +/- 0.63%) (p = 0.011 and p <0.001, respectively). The prevalence of LV mechanical dyssynchrony (SDI >5.14%, mean + 2 SDs of controls) in groups I and II was 72% and 67%, respectively. In 27 patients with right ventricular pacing, LV SDI values were correlated negatively with the LV ejection fractions (r = -0.74, p <0.001). The times to minimum regional volume were significantly longer in lateral, posterior, and inferior segments in group I and septal and inferior segments in group II compared to those in group III (p <0.05). Compared to patients without LV dyssynchrony, patients with LV dyssynchrony had lower LV ejection fractions (p <0.001), had shorter RR intervals (p <0.001), and tended to have dual-chamber pacing (p = 0.088) but had similar durations of pacing, QRS durations, and positions of pacing wires (epicardial vs endocardial). In conclusion, permanent right ventricular pacing in childhood has a negative effect on LV systolic function through the induction of mechanical dyssynchrony, the magnitude and pattern of which differ between congenital and acquired heart block.