Clinical and genetic profile of congenital long QT syndrome in Hong Kong: a 20-year experience in paediatrics.

INTRODUCTION: Congenital long QT syndrome (LQTS) is a genetically transmitted cardiac channelopathy that can lead to sudden cardiac death. This study aimed to report the clinical and genetic characteristics of all young patients diagnosed with LQTS in the only tertiary paediatric cardiology centre in Hong Kong. METHODS: This is a retrospective review of all paediatric and young adult patients diagnosed at our centre with LQTS from January 1997 to December 2016. The diagnosis of LQTS was established with a corrected QT interval (QTc) ≥480 ms, Schwartz score of >3 points, or the presence of a pathogenic mutation. RESULTS: Fifty-nine patients (33 males) from 52 families were included, with a mean age of 8.17 years (range, 0.00-16.95 years) at presentation. Five patients had concomitant congenital heart diseases. The mean follow-up duration was 5.33 ± 4.65 years. The mean QTc in the cohort was 504 ± 47 ms. They presented with syncope and convulsion (49%), cardiac arrest (10%), bradycardia and neonatal atrioventricular block (12%). Fifteen (25%) patients were asymptomatic at diagnosis. Thirty-eight (64.4%) patients were confirmed to have a pathogenic mutation for LQTS genes. Forty-five (76.3%) patients received beta blocker therapy. Thirteen (22.0%) patients required implantable cardioverter defibrillator. There was no mortality in the study period. The 1-, 5-, and 10-year breakthrough cardiac event-free rates were 93.0%, 80.7%, and 72.6%, respectively. CONCLUSION: Identification of the disorder, administration of beta blockers, and lifestyle modification can prevent subsequent cardiac events in LQTS. Genotyping in patients with LQTS is essential in guiding medical therapy and improving prognosis.

Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

Clinical and genetic profile of catecholaminergic polymorphic ventricular tachycardia in Hong Kong Chinese children.

OBJECTIVE: To report our experience in the management of catecholaminergic polymorphic ventricular tachycardia in Hong Kong Chinese children. METHODS: This case series study was conducted in a tertiary paediatric cardiology centre in Hong Kong. All paediatric patients diagnosed at our centre with catecholaminergic polymorphic ventricular tachycardia from January 2008 to October 2014 were included. RESULTS: Ten patients (five females and five males) were identified. The mean age at presentation and at diagnosis were 11.0 (standard deviation, 2.9) years and 12.5 (2.8) years, respectively. The mean delay time from first presentation to diagnosis was 1.5 (standard deviation, 1.3) years. They presented with recurrent syncope and six patients had a history of aborted cardiac arrest. Four patients were initially misdiagnosed to have epilepsy. Catecholaminergic polymorphic ventricular tachycardia was diagnosed by electrocardiogram at cardiac arrest (n=2), or provocation test, either by catecholamine infusion test (n=6) or exercise test (n=2). Mutations of the RyR2 gene were confirmed in six patients. Nine patients were commenced on beta-blockers after diagnosis. Despite medications, three patients developed aborted or resuscitated cardiac arrest (n=2) and syncope (n=1). Left cardiac sympathetic denervation was performed in five patients and an implantable cardioverter defibrillator was implanted in another. There was no mortality during follow-up. CONCLUSIONS: Catecholaminergic polymorphic ventricular tachycardia should be considered in children who present with recurrent syncope during exercise or emotional stress. Despite beta-blocker treatment, recurrent ventricular arrhythmias occur and may result in cardiac arrest.

Transcatheter ablation of atrioventricular junctional re-entrant tachycardia in children and adolescents in Hong Kong: comparison of cryothermal with radiofrequency energy.

OBJECTIVE: To compare the outcome of cryothermal and radiofrequency energy transcatheter ablation of atrioventricular junctional re-entrant tachycardia in children and adolescents. DESIGN: Case series with internal comparison. SETTING: Two hospitals in Hong Kong. PATIENTS: Consecutive transcatheter ablation procedures for atrioventricular junctional re-entrant tachycardia in children and adolescents in our unit from August 2000 to September 2008 were retrospectively reviewed. Radiofrequency ablation was performed from August 2000 to June 2005, and cryoablation from July 2005 to September 2008. MAIN OUTCOME MEASURES: Demographic data, outcome and procedural details. RESULTS: Thirty-eight procedures were reviewed. The radiofrequency ablation group (n=20) and cryoablation group (n=18) had similar demographic characteristics, except that there were more patients with congenital heart disease in the latter group (P=0.03). Acute procedural success rate was 100% in both groups. One patient from the radiofrequency ablation group had recurrence of atrioventricular junctional re-entrant tachycardia. The frequency of post-ablation persistent heart block was higher in the radiofrequency ablation than cryoablation group (10% vs 0%, P=0.17), but this difference was not statistically significant. A shorter fluoroscopy time was noted in the cryoablation group (31 ± 13 vs 38 ± 18 minutes; P=0.03). CONCLUSIONS: Transcatheter cryoablation for atrioventricular junctional re-entrant tachycardia in children and adolescents is as effective as radiofrequency ablation over the medium term. It has an excellent safety profile in terms of avoiding heart block.

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.

An evolving role of transesophageal echocardiography for the monitoring of interventional catheterization in children.

BACKGROUND AND HYPOTHESIS: Transesophageal echocardiography (TEE) is increasingly utilized for the monitoring of interventional cardiac catheterization in children. The initial nondiscriminant use is giving way to a more selective approach. The current role and usefulness of this imaging modality are described. METHODS: Between 1991 and 1995, 44 patients (mean age 7.4 +/- 5 years, weight 22.8 +/- 14.2 kg) underwent interventional cardiac catheterizations performed under TEE monitoring. The interventional procedures included (1) those involving creation, enlargement, or closure of an interatrial communication; (2) balloon dilatation of stenotic lesions; and (3) occlusion of arterial ducts. Transesophageal echocardiographic monitoring was judged to be either of great value, contributory, or of little use if the interventional procedure and choice of instrument relied heavily upon, was guided, or not affected by the information obtained from the ultrasonic investigation, respectively. RESULTS: Transesophageal echocardiography was judged to be of great value in the monitoring of 18 (40%) procedures involving either the creation, enlargement, or closure of interatrial communications. This included 4 transseptal punctures, 4 blade septectomies for relieving restrictive atrial septal defects (n = 3) and an enlargement of the communication between the superior and inferior chambers of the divided left atrium in cortriatriatum, and 11 closures of a secundum atrial septal defect. Only the ultrasonic monitoring could clearly visualize the interatrial partition to provide real-time guidance on the positioning of the instrument to carry out the invasive procedures. Transesophageal echocardiography provided clear images of the hinge points of the aortic and mitral valves, the dimension of the narrowed pulmonary venous pathway in patients after venous switch operation. This facilitated the choice of the correct size of the balloon for dilatation in 11 patients (24%) and provided immediate postdilatation hemodynamic assessment. As for balloon dilation of subvalvar ventricular outflow tract obstruction (n = 3), aortic coarctation (n = 6), and occlusion of persistent arterial duct (n = 7), TEE offered no obvious advantage over fluoroscopy with angiography. The monitoring was judged to be of little value for the 16 (36%) procedures. CONCLUSION: Transesophageal echocardiographic monitoring is of great value in interventional procedures involving the atrial septum and enhances interventional procedures involving obstructive lesions of the left heart in children.

Improving aerobic power in primary school boys: a comparison of continuous and interval training.

The purpose of this study was to assess whether the magnitude of change in aerobic power was different in boys (mean age 10.25 +/- 0.50 y) who followed a high-intensity interval training protocol, compared to those who followed a moderate-intensity continuous training protocol. Boys were assigned to either a control group (n = 15), a continuous training group (n = 10), or an interval training group (n = 10). They completed peak oxygen uptake tests at baseline and following an 8-week training period. The control group continued with normal activity habits, whilst the continuous training group followed a 20-minute steady-state cycle protocol at 80-85 % of the maximal heart rate, and the interval training group completed 30-s sprints on a cycle ergometer, interspersed with active rest periods. The two training protocols were designed to incur similar cardiovascular work over the 20 minutes of each training session. Significant increases (p < 0.05) in peak oxygen uptake were noted for both the interval and continuous training groups. The interval training group showed marked pre- to post-increases in both peak oxygen pulse, oxygen pulse at the ventilatory threshold, and ventilatory threshold that were not apparent in the continuous group boys. It would appear that a high-intensity interval protocol confers a different training effect in comparison to continuous steady-state training in boys. Possible mechanisms that underpin these adaptations may include increased blood volume and a concomitant adjustment in stroke volume.

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.

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 beta = 0.22, p = 0.02), systolic blood pressure (standardised beta = 0.28, p = 0.01), log serum hs-CRP concentration (standardised beta = 0.21, p = 0.017), and patient grouping (standardised beta = -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.

Evolving management for critical pulmonary stenosis in neonates and young infants.

Over the years, management of critical pulmonary stenosis in young infants has evolved from surgical reconstruction of the right ventricular outflow tract and closed pulmonary valvotomy to transcatheter balloon valvoplasty. Our study aimed at evaluating how the changing policy for management had affected the immediate and long term outcomes of babies with this cardiac lesion. Interventions were made in 34 infants at a median age of 8.5 days (2-90 days). Reconstruction of the right ventricular outflow tract reconstruction was performed in 10 patients, closed pulmonary valvotomy in 13, and balloon valvoplasty in 11. Initial procedure-related mortality was 50%, 15% and 0% respectively. Multivariate analysis revealed transannular patching of the right ventricular outflow tract, and male sex, to be significant factors for death. For the 27 survivors, the ratio of right ventricular to systemic systolic pressure decreased from 1.6 +/- 0.3 to 0.3 +/- 0.2 after reconstruction of the outflow tract, 1.8 +/- 0.5 to 0.8 +/- 0.4 after closed valvotomy, and 1.8 +/- 0.6 to 0.9 +/- 0.3 after balloon valvoplasty. The decrease was significantly greater after patch reconstruction (p=0.025) that required no further reinterventions. The overall rate of reintervention for the survivors was 37% (10/27). The freedom from reintervention after closed valvotomy was 82%, 64% and 51% at 1, 5 and 10 years respectively. The figure remained at 78% at both 1 and 5 years (p=0.66) after balloon valvoplasty. The higher reintervention rate for closed valvotomy corresponded to the significantly greater residual gradient across the pulmonary valve noted on follow-up (p=0.01). Reinterventions included balloon dilation (n=6), reconstruction of the outflow tract (n=4), and 1 each of ligation of an arterial duct and systemic-pulmonary arterial shunting. The risk factor for reintervention was a hypoplastic right ventricle. In conclusion, transcatheter balloon valvoplasty appears to be the optimum initial approach in view of its low mortality, efficacy at relieving the obstruction, and low rate of reintervention.

Radiofrequency catheter ablation of left-sided accessory pathways using a transeptal technique and specialized long intravascular sheaths. Efficacy, recurrence rate and complications.

49 patients with 51 left-sided accessory pathways underwent radiofrequency catheter ablation for symptomatic supraventricular tachycardia via the transeptal route using specialised long vascular sheaths with compound curves. The procedure was successful in 45 patients (92%). The mean fluroscopic time was 22.5 +/- 15.2 mins and the mean procedure time was 1.7 +/- 0.5 hours. Pericardial tamponade occurred in 2 patients (4%) and 2 patients (4%) required switching to the retrograde transaortic route for successful ablation of the pathways. During the period of follow-up of 16.8 +/- 6.9 months, clinical recurrence occurred in 2 patients (4%). In conclusion, the transeptal route of radiofrequency catheter ablation is a useful alternative strategy to the transaortic approach with good long term results. The use of specialised sheaths may help in stabilisation of the catheter during the procedure which can generate more adequate lesions and consequently a lower recurrence rate.

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.

Tracheobronchography and angiocardiography of paediatric cardiac patients with airway disorders.

OBJECTIVE: We report our experience in combining tracheobronchography and angiocardiography in the assessment of a selected cohort of paediatric cardiac patients with problematic airway disorders. METHODOLOGY: The clinical records of 11 patients who underwent 17 studies at a median age of 5.5 months (range 3 months to 10.8 years) were reviewed. Tracheobronchography and angiocardiography were performed under general anaesthesia using a non-ionic contrast agent. The findings were compared with those of flexible bronchoscopy and magnetic resonance imaging (MRI). RESULTS: Seven patients had cardiac lesions associated with vascular anomalies potentially compressing the airway, while four had no identifiable aberrant or enlarged vessels. All examinations but one were performed without complications. Tracheobronchography demonstrated extrinsic vascular compression with secondary airway malacia in three (27%), intrinsic tracheobronchial stenosis in five (45%), and airway malacia in three patients (27%). Precise measurement of the airway calibre and real-time fluoroscopic monitoring facilitated transcatheter tracheobronchial interventions (six balloon dilations, three stent implantations) in four patients. In conjunction with angiocardiography, cine-tracheobronchography provided detailed information on the spatial relationship between vascular and airway structures in all patients; allowed dynamic assessment of airway malacia; and facilitated preoperative planning in six patients. In contrast, bronchoscopy failed to differentiate malacia from extrinsic compression in four patients (36%), while MRI, performed in six patients, was unsatisfactory in one due to a motion artefact and failed to diagnose airway malacia and extrinsic compression in three patients. CONCLUSIONS: Tracheobronchography is relatively safe in paediatric cardiac patients. Combined tracheobronchography and angiocardiography, a less operator-dependent imaging modality compared to bronchoscopy and MRI, delineated the airway and vascular anatomy in detail; facilitated preoperative planning; and permitted transcatheter tracheo-bronchial interventions. The dynamic capability of tracheobronchography supplements that of flexible bronchoscopy and MRI in the diagnosis of airway malacia.