Hui-Chi Chen

Prevalence of Congenital Heart Disease at Live Birth in Taiwan

OBJECTIVES To investigate the prevalence at live birth of congenital heart disease (CHD) in Taiwan. STUDY DESIGN Patients with CHD born from 2000 to 2006 were identified from National Health Insurance databases. RESULTS CHD prevalence was 13.08 per 1000 live births: 12.05 (simple, 10.53; severe, 1.51) in male infants and 14.21 (simple, 12.90; severe, 1.32) in female infants. Ventricular septal defect (VSD; 4.0) was the most common defect, followed by secundum atrial septal defect (ASDII; 3.2), patent ductus arteriosus (PDA; 2.0), pulmonary stenosis (PS; 1.2), tetralogy of Fallot (TOF; 0.63), coarctation of aorta (CoA; 0.25), transposition of great arteries (TGA; 0.21), endocardial cushion defect (ECD; 0.20), double outlet of right ventricle (DORV; 0.15), total anomalous pulmonary venous return (TAPVR; 0.11), aortic stenosis (0.09), hypoplastic left heart syndrome (HLHS; 0.062), Ebstein anomaly (0.047), and tricuspid atresia (0.046). Female predominance was observed in VSD, ASDII, PDA, and ECD; and male predominance was observed in TGA and TOF. Ratios of western prevalence to our Asian prevalence were high for HLHS (3.68-4.5), CoA (1.13-1.96), TGA (1.09-1.83), and tricuspid atresia (1.09-2.57), but low for PS (0.15-0.99), TOF (0.41-0.92), and possibly ASDII. CONCLUSIONS In this Asian population, the prevalence of CHD was at the high end of the reported range, with more PS and TOF, but fewer left-sided obstructions, TGA, and tricuspid atresia.

Prevalence and the Long-Term Coronary Risks of Patients With Kawasaki Disease in a General Population <40 Years A National Database Study

Background— Patients with Kawasaki disease (kDa) may develop coronary arterial lesions and subsequent coronary events. The first reported case in Taiwan was in 1976, and the annual incidence from 2003 to 2006 was 69/100 000 children < 5 years. A population study from Taiwan, a country with a high incidence of kDa, national health insurance, and easily accessible medical care, would adequately reflect the long-term risk. Methods and Results— We retrieved the data of kDa patients from a national health insurance 2000 to 2010 database of Taiwan, a country with a child health index similar to those in the United States. The occurrence of coronary complications and interventions was identified by the respective International Classification of Diseases, Ninth Revision, codes. The prevalence of kDa in the population < 40 years was 34.9/100 000 (male/female ratio, 1.47). Coronary complications occurred in 1254 patients (5.37%; male/female ratio, 2.19), with an average annual risk of 2.4% (2.7% for males and 2.0% for females). An acute myocardial infarction occurred in 19 patients (0.08%; 18 males and 1 female), of whom one third were aged between 10 and 15 years (median, 15.7 years; range, 0.7–36.7 years). A coronary intervention was performed by catheterization in 18 patients (all males) at a median age of 24.5 years and by surgery in 10 patients (male/female ratio, 4.0) at a median age of 21.7 years, with mortality at discharge being 0% and 25%, respectively. Conclusions— This study estimated the overall prevalence of kDa (≈1/2940) in a population < 40 years. They, particularly the males, carry long-term coronary risks from a young age. Risk stratification for a timely coronary intervention and risk modification are mandatory.

Long-Term Survival and Unnatural Deaths of Patients With Repaired Tetralogy of Fallot in an Asian Cohort

Background— Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease in Taiwan. This study investigates the long-term survival and risks of TOF in an Asian cohort. Methods and Results— This study enrolled 819 consecutive patients with TOF (61.1% male), who received total correction between 1970 and 2002, as participants. Patient medical records were reviewed, and the survival status of those out of contact was confirmed by death records retrieved from the National Health database. The mean (±SD) patient age at cardiac repair was 6.5±7.6 years, and a prior shunt operation was performed in 119 (14.5%) of the patients. At cardiac repair, a transannular patch for right ventricle outlet reconstruction was required in 444 (54.2%) of the patients. After 13 808 patient-years of follow-up, the 30-year survival rate was 90.5%. The annual mortality rate increased from 0.123% in the initial 15 years after repair to 0.395% thereafter (P<0.05). The presence of major aortopulmonary collateral arteries, older operative age, and previous shunt operation are independent risks of late cardiac deaths. Secondary to cardiac mortality, unnatural deaths (accident and suicide) accounted for 27.6% of late deaths, significantly higher compared with that of the general population (odds ratio, 2.18; P=0.028). Conclusions— In this Asian TOF cohort, except for a late decrease after 15 years, long-term survival after cardiac repair was satisfactory. Although cardiac death was the most common cause of late death, accidents or suicide may also be associated with late mortality, suggesting a potential role for psychosocial support.

Epidemiological Profile of Marfan Syndrome in a General Population: A National Database Study

OBJECTIVE To explore the current epidemiological profile of Marfan syndrome in a general population. PATIENTS AND METHODS Patients who had received a diagnosis of Marfan syndrome were identified from the Taiwan National Health Insurance database records from January 1, 2000, through December 31, 2012 (average population size, 22,765,535). Cardiovascular events and interventions were identified by using the respective International Classification of Diseases codes. RESULTS We identified 2329 patients (58% men) with Marfan syndrome. The overall prevalence was 10.2 (95% CI, 9.8-10.7) per 100,000 individuals, with peaks at the age of 15 to 19, 10 to 14, and 20 to 24 years. The minimal birth incidence of 23.3 (95% CI, 21.7-23.3) per 100,000 individuals was estimated in those aged 20 to 29 years. The average annual mortality was 0.23% (69 deaths), mostly owing to cardiac causes (including dissection and sudden death in 40 patients, 58%). Aortic dissection occurred in 226 patients (10%; 61% men) at a mean age of 36.6±10.7 years. The probability of freedom from dissection was 99%, 80%, and 66% at the age of 20, 40, and 50 years, respectively. Of the 69 deaths and 226 dissections during the follow-up period, more than half of the cases occurred before the age of 40 years. Cardiovascular intervention was performed in 360 patients, with early mortality being higher in the emergent operation group (8%) than in the elective group (0%). CONCLUSION From this national cohort study, the minimal birth incidence was 23.3 per 100,000 individuals, that is, possibly 1 patient with Marfan syndrome per 4286 people. Despite medical advances, aortic dissection still occurs in about one-tenth of the patients and carries a high mortality risk. Early diagnosis and timely medical interventions are warranted.

Population-based study of pediatric sudden death in Taiwan

OBJECTIVES We sought to estimate the incidence of pediatric sudden death (SD) in Taiwan. STUDY DESIGN Cases of SD were identified from National Health Insurance databases, 2000 to 2006. RESULTS In the Taiwan pediatric population (age, 0 to 18 years; 5.44 million), the neonatal, infant, postneonatal infant, and under-5 years mortality rates were 3, 6, 2.81, and 8.02 per 1000 live births, and the 1 to 18 years mortality rate was 33 per 100 000 person-years. There were 1528 SDs (59% boys). In the population 1 to 18 years, annual incidence of SD was 2.7 (95% confidence interval, 2.6 to 2.9), ranging from 0.7 (11 to 12 years) to 6.1 (1 to 2 years) per 100 000. Male predominance was noted (3.2 vs 2.2 per 100 000), particularly in groups ages 16, 17, and 18 years. The proportionate mortality ratio by SD ranged from 1.8% to 12.0% (8.9 +/- 2.2%), being lowest in the group ages 11 to 12 years. In infants, the incidence of SD was 0.36 per 1000 live births, and the proportionate mortality ratio by SD was 1.0% and 11.7% in the neonates and postneonatal infants. CONCLUSIONS The incidence of pediatric SD in Taiwan, an Asian country with a child health care index comparable with that in the United States, was within the range from Western reports and indicated male predominance and a nadir around 11 to 12 years.

Arrhythmic burdens in patients with tetralogy of Fallot: A national database study

BACKGROUND Tetralogy of Fallot (TOF) is a common cyanotic congenital heart disease with increasingly recognized late morbidity. OBJECTIVE The purpose of this study was to explore the long-term outcome by using a national database of Taiwan, a country with national health insurance and easily accessible medical care. METHODS Data on TOF patients were retrieved from database records from 2000 to 2010. Complications and therapies were identified by their respective codes. RESULTS We identified 4781 TOF patients (prevalence 0.63/1000 in pediatric patients and 0.06/1000 in adult patients). Arrhythmias were identified in 219 patients (8.3% for adult patients and 2.8% for pediatric patients): 160 tachycardia and 59 bradycardia (4 with tachy-bradycardia syndrome). The occurrence of arrhythmias was associated with higher mortality (excluding cardiac surgical death, 15.6% vs 8.6%, P = .001). Patients with atrial fibrillation were the oldest (median age 44.3 years), followed by those with tachy-bradycardia syndromes (32.4 years) and atrial flutter (31.5 years). The incidence of nonperioperative tachycardia increased with age (1.4%, 1.7%, 3.3%, 5.2%, 10.2%, and 16.9% in age group 0-9, 10-19, 20-29, 30-39, 40-49, and ≥50 years, respectively). Tachycardia therapy (ablation and implantable cardioverter-defibrillator) was administered in 20.4% (annually 2.4%) of patients with nonperioperative tachycardia. In the subgroup born 2000-2010 with complete postnatal data, mortality was 15.1% (296/1960), and 1-, 5-, and 10-year survival was 0.911, 0.826, and 0.788, respectively. Risk of atrioventricular block requiring a pacemaker was 0.6%. CONCLUSION Arrhythmias are common in TOF patients and increase mortality risk. Medical needs because of tachycardia often appear late in adulthood.

Prevalence, Mortality, and the Disease Burden of Pediatric Congenital Heart Disease in Taiwan

BACKGROUND In Taiwan, the incidence of congenital heart diseases (CHDs) and severe CHDs was 13.08 and 1.51 per 1000 live births, respectively. This study further elucidates the prevalence and mortality of pediatric CHD patients in Taiwan. METHODS From the National Health Insurance database 2000-2010, we retrieved the data of CHD patients (aged 0-18 years). Mortality data were obtained from the national death statistics. RESULTS In total, 45,119 pediatric CHD patients were identified, given the prevalence at 918.0 per 100,000 (107.1 for severe CHD and 853.8 for simple CHD). Ventricular septal defect, ostium secundum-type atrial septal defect, patent ductus arteriosus, pulmonary stenosis, and tetralogy of Fallot were the five most frequently diagnosed CHDs. In those aged 0-6 years, the prevalence was 1233.7 per 100,000 (123.5 for severe CHD and 1149.6 for simple CHD). The age-specific prevalence of both simple and severe CHDs declined rapidly after the age of 10 years. From the death registry, we noted that more than 90% of CHD-related deaths occurred before the age of 5 years. The probability of cardiac death in CHD patients during infancy was 4.5%, with the cumulative probability reaching 5.44%, 5.68%, and 6.04% by the ages of 5, 10, and 20 years, respectively. CONCLUSION Because most CHD deaths occurred within the first 5 years of life (mainly during infancy), the relatively low prevalence of CHDs in the population aged 0-18 years (918/100,000; 74% for those between 0 years and 6 years of age) and the rapid decline in the age-specific prevalence of CHD after the age of 10 years was attributed to noncompliance of the children to medical follow-up after they began schooling.

Severe Bacterial Infection in Patients with Heterotaxy Syndrome

OBJECTIVE To determine the incidence of sepsis in patients with heterotaxy syndrome. STUDY DESIGN From our institutional database, we identified patients with heterotaxy syndrome and other complex congenital heart disease (CHD) born between 2001 and 2011. Severe bacterial infection was defined as sepsis with positive culture result or infection with abscess formation. RESULTS We enrolled 95 patients with heterotaxy syndrome (88 with right atrial isomerism and 7 with left atrial isomerism) and 142 patients with complex CHD. With 1026 person-years follow-up, the 5-year survival was 52% and 65.7% in heterotaxy and complex CHD groups, respectively (P = .239). Community-acquired severe bacterial infection occurred only in heterotaxy syndrome (13 episodes in 10 patients, 3 of whom had spleen noted at imaging study) with 2- and 5 years cumulative severe bacterial infection rate of 9.6% and 14.5%, respectively. The overall mortality rate of those with community-acquired severe bacterial infection was 31%. Pneumococcus and Citrobacter freundii were the most common pathogens. Nosocomial severe bacterial infection occurred in 33.3% of all patients and 12.5% of all procedures. The rates (0.59 and 0.52/100 hospitalization days in heterotaxy and complex CHD group) and the pathogens of nosocomial severe bacterial infection were similar between heterotaxy and complex CHD groups. CONCLUSIONS Patients with heterotaxy syndrome are at high risk for community-acquired severe bacterial infection and also have high mortality rate whether the spleen is present or not. The risk of nosocomial severe bacterial infection seems similar to that of patients with other complex CHD.

Epidemiological profile of Wolff–Parkinson–White syndrome in a general population younger than 50 years of age in an era of radiofrequency catheter ablation

BACKGROUND The prevalence of Wolff-Parkinson-White (WPW) syndrome varies between 0.68 and 1.7/1000. The epidemiological profile may be modified after the introduction of transcatheter interventions. OBJECTIVES The aim of this study is to investigate the epidemiological trends of the WPW syndrome in a general population during a period with available and reimbursed transcatheter ablation. METHODS AND RESULTS Data of WPW patients <50 years old were retrieved from our national database (2000-2010). We identified 6086 (61% male) patients, accounting for an overall prevalence of 0.36/1000 with a peak of 0.61/1000 in ages 20-24 years. The risk of death and sudden death was 0.071% and 0.02% per patient-year, respectively. The 42 deaths occurred at a median age of 29 years. Associated congenial heart disease was noted in 158 (2.6%) patients, including 42 with Ebsteins anomaly that increased the mortality risk (P=0.001, OR=8.5). In those without congenital heart disease, myocardial dysfunction occurred in 115 (1.9%) patients and increased the risk of death (P<0.001, OR=10.6) and sudden death. Radiofrequency catheter ablation was performed in 2527 patients at a median age of 25.7 years (4.54% per patient-year, discharge mortality 0.16%); 11 (0.4%) before the age of 5, and 2231 (88%) after the age of 15. Whereas repeated ablation procedures accounted for 6.0% of the procedures, those in Ebsteins patients were 25%. CONCLUSION Radiofrequency catheter ablation is already a common treatment for WPW patients, particularly during young adulthood, which accounts for a lower prevalence. Myocardial dysfunction and associated congenital heart disease remain as risks of mortality.

Abnormal Matrix Remodeling in Adolescents and Young Adults with Kawasaki Disease Late after Onset

BACKGROUND Patients with a history of Kawasaki disease (KD), have been found to have pericoronary and myocardial fibrosis. Serum biomarkers of fibrosis may be sensitive indices for detection of these late cardiac complications in KD patients. METHODS We studied a cohort of 60 adolescents and young adults comprising 10 KD patients with persistent coronary artery lesions (CAL) occurring at a mean (SD) time of 14.5 (4.4) years after disease onset, 25 KD patients with no CAL after disease onset, and 25 healthy age-matched volunteers. We compared laboratory data from the patients and volunteers, including lipid profile, liver function, amino-terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), and MMP-9:TIMP-1 ratios. Severity of CAL was determined on the basis of computed tomography determinations of the frequency of aneurysms and the extent of coronary stenosis/occlusion, thrombosis, and calcification. RESULTS Increased PIIINP and decreased MMP-9 and TIMP-1 concentrations and decreased MMP-9:TIMP-1 ratios were found not only in KD patients with persistent CAL but also in KD patients without CAL, although to a lesser extent in the latter group. In KD patients, the concentrations of PIIINP were positively associated with the severity of coronary stenosis/occlusion (r = 0.72, P = 0.011) and with the extent of coronary thrombus (r = 0.64, P = 0.014). The concentrations of high-sensitivity C-reactive protein, however, did not differ across groups. CONCLUSIONS Our results demonstrate alterations in extracellular matrix biomarkers in KD patients, suggesting enhanced collagen synthesis and ameliorated degradation in adolescents and young adults late after the onset of KD. We also observed an association between the concentrations of PIIINP and the extent of coronary stenosis/occlusion or thrombosis in KD patients, a finding that needs confirmation in further studies.