Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study.

BACKGROUND: Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB). AIM: To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice. METHODS: This population-based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first-line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors. RESULTS: During a median follow-up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4-year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%-2.2%). Significant risk factors were cirrhosis (adjusted sub-distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82-4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45-4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03-1.42) and male sex (aSHR, 1.58; 95% CI, 1.04-2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4-year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%-1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%-2.0%). CONCLUSIONS: Severe flares with hepatic decompensation were observed in 1%-2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care.

Atrial fibrillation in adult congenital heart disease and the general population.

BACKGROUND: Atrial fibrillation (AF) in adult patients with congenital heart disease (ACHD) may appear early, depending on individual characteristics. OBJECTIVES: The goals of this study were to investigate the epidemiological spectrum of AF in the entire cohort of ACHD and compare it with that in the general population. METHODS: A retrospective study was performed in the nationwide cohort 2000-2014 with AF onset during 2003-2014. RESULTS: In the cohort of ACHD, 2350 patients had AF; the incidence increased with age, plateauing around age 70. In patients aged 25-29, 45-49, 65-69, 75-79, and ≥80 years, the annual incidence was 1.3, 7.9, 20.6, 23.7, and 21.4/1000 per year, respectively. In the general population without CHD, 347,979 patients had AF; the annual incidence was <1/1000 per year in those aged <55 years but increased steadily with age (3.6, 8.6, and 14.2/1000 per year in aged 65-69, 75-79, and ≥80 years, respectively). Compared with individuals without ACHD, ACHD patients aged <50 years and those aged both 50-54 and 55-59 years exhibited a 20-fold and 10-fold higher incidence of AF, respectively. Patients with complex congenital heart disease and Ebstein's anomaly had the highest risk of AF (cumulative risk >10% by age 50 and >20% by age 60), followed by those with tetralogy of Fallot, tricuspid atresia, endocardial cushion defect, and secundum atrial septal defect (cumulative risk >5% by age 50 and >10% by age 60). CONCLUSION: Compared with individuals without ACHD, AF in patients with ACHD likely appeared 30 years earlier, with a 10- to 20-fold higher incidence plateauing around age 70. Yet, incidence in individuals without ACHD continued to increase. AF burden in patients with ACHD is not expected to increase in a never-ending way.

Policy-Driven Post-Acute Care Program Lowers Mortality Rate and Medical Expenditures After Hospitalization for Acute Heart Failure: A Nationwide Propensity Score-Matched Study.

OBJECTIVE: The beneficial effects of multidisciplinary disease management programs have been demonstrated. The present study investigated the effects of a policy-driven, health insurance-reimbursed, heart failure (HF) post-acute care (PAC) program on mortality, health care service utilization, and readmission expenses for patients following hospitalization for HF. DESIGN: This was a retrospective propensity score-matched cohort study using the Taiwan National Health Insurance Research Database. SETTING AND PARTICIPANTS: In total, 4346 patients (2173 receiving HF-PAC and 2173 controls) with left ventricular ejection fraction of ≤40% who were discharged following hospitalization for HF were included for analysis. METHODS: All patients were followed up after discharge for all-cause mortality, emergency visits within 30 days, and length of stay and medical expenses for readmission within 180 days after discharge. RESULTS: After propensity score matching, baseline characteristics of the HF-PAC and control groups were similar. During a mean follow-up period of 1.59 ± 0.92 years, according to the Cox multivariable analysis, HF-PAC reduced mortality by 48% compared with the control group, independent of traditional risk factors (hazard ratio = 0.520, 95% CI = 0.452-0.597, P < .001). Kaplan-Meier curves revealed that HF-PAC was associated with a higher cumulative survival rate (log-rank = 96.43, P < .001). HF-PAC also decreased the frequency of emergency visits after discharge by 23% in the 30 days post discharge and decreased length of stay and medical expenses related to readmission by 61% and 63%, respectively, in the 180 days post discharge (all P < .001). CONCLUSIONS AND IMPLICATIONS: HF-PAC reduces short-term all-cause emergency visits, length of stay, and medical expenses for all-cause readmission and all-cause mortality in patients discharged following hospitalization for HF. Our findings suggest that PAC should include care continuity, optimal adaptation of transitional care components, and HF cardiologist engagement with multidisciplinary coordination.

Epidemiology of Cardiomyopathy in Taiwanese Population Aged Younger Than 65 Years.

Background: Few studies have investigated the epidemiology of cardiomyopathy (CMP) in the general population in Taiwan. The aim of this study was to investigate this issue. Methods: We identified patients aged < 65 years and diagnosed with CMP between 2001 and 2014 from the National Health Insurance Database of Taiwan 2000-2014. Those with known or presumed causes of CMP were further identified. Results: We identified 38,868 CMP patients (male/female = 2.13). Half had known or presumed causes of CMP, including coronary artery disease (23.6%), congenital heart disease (1.6%), metabolic disease (8.4%), conduction disturbance/dyssynchrony (2.2%), myocarditis (0.5%), muscular dystrophy (1.42%), Kawasaki disease (0.2%), nutrition problems or alcoholism (2.9%), and unspecified causes (12.4%). The incidence rates of CMP without known causes were 1.13 and 8.70 per 100,000 person-years in pediatric (0-19 years) and adult (20-64 years) populations, respectively. After an initial peak during infancy (9.16 per 100,000 person-years), the incidence declined to a nadir in those aged from 5 to 14 years, and then steadily increased during adulthood (26.51 per 100,000 person-years in those aged 60-64 years). Although mortality was higher in the pediatric (11.4%) than in the adult (1.5%) patients, the proportion of sudden death to all deaths was similar in the pediatric (9.9%) and adult (10.5%) patients. Conclusions: This study provides an epidemiological continuum of CMP in a Taiwanese population aged < 65 years. The results revealed an initial peak during infancy, followed by a decline in adolescence and a subsequent steady rise. The prognosis was poorer in the pediatric patients, and poorest in the infants. However, the risk of sudden death was the same in the adult and pediatric patients.

The Postnatal Risk, Resuscitation Success Rate and Outcomes of Pediatric Sudden Death in Taiwan.

BACKGROUND: The epidemiology of pediatric potentially sudden death (SD) events and the rescue rate remain unclear. METHODS: We established a birth cohort (2000-2014) from a national database 2000-2015. RESULTS: Of 3,097,277 live births, we identified 3126 children (56.1% male) with potentially SD events, including 887 who were rescued. The cumulative risk of potentially SD events for each neonate was 0.30, 0.62, 0.91, 1.05, and 1.13 per 1000 by 2 months, 0, 5, 11 and 14 years of age, respectively. Overall, 28.3% of the children were rescued from SD events, with a higher rate in neonates (69.6%) but lower rate in postneonatal infants. A cardiac diagnosis was noted in 596 (19.1%) patients, including congenital heart disease (CHD) (388), cardiac arrest (151), cardiomyopathy (23), myocarditis (12), Kawasaki disease (7) and arrhythmia (36). Coexisting severe CHD and events in postneonatal infancy were associated with a lower chance of resuscitation, whereas events within 1 week of age had a higher chance of resuscitation. Anoxic brain damage was noted in 174 (19.7%) patients and late death occurred in 348 (39.3%) patients after being rescued from SD. Late death was more common in males, those with anoxic brain damage, those with coexisting severe CHD, and postneonatal infants. CONCLUSIONS: In this birth cohort study, the postnatal cumulative risk of potentially SD events was 1 in 885 newborns by 14 years of age. Postneonatal infants and those with coexisting severe CHD had the highest risk and worst outcomes.

Existing Data Sources in Clinical Epidemiology: The Taiwan National Health Insurance Laboratory Databases.

This paper provides an introduction to laboratory databases established by Taiwan National Health Insurance Administration (NHIA) since 2015 and released for research since June 2017. The National Health Insurance (NHI) is a government-run single-payer program introduced in 1995 that now covers more than 99% of 23 million Taiwanese citizens. To prevent duplication of medication prescriptions and laboratory test and examination prescriptions, contracted health care providers are required to upload the results of laboratory tests and reports of examinations to the NHIA. The cumulative number of laboratory test results was 5.64 billion from January 2015 to the end of August 2020 for 602 types of test. There are 35 variables for each laboratory test result stored in the databases that can be used for research. However, different hospitals might use different format in reporting the results. The researchers therefore have to develop algorithms to include and exclude incompatible records and to determine whether the results are positive or negative (normal or abnormal). The NHIA suggests that researchers release their source codes of algorithms so that other researchers can modify the codes to improve inter-study comparability. Through the unique personal identification number, the laboratory data can be linked to NHI inpatient and outpatient claims data for further value-added analyses. Non-Taiwanese researchers can collaborate with Taiwan researchers to access the NHI laboratory databases.

Incidence and Postnatal Profile of Fontan Patients by Adolescence from a Nationwide Birth Cohort.

BACKGROUND: Although the Fontan procedure is associated with a variety of long-term complications, it is the mainstay treatment for congenital heart disease with a functioning single ventricle. Data concerning the epidemiological profile are scarce. METHODS: We investigated the current epidemiological profile using a 2000-2008 nationwide birth cohort from a 2000-2014 database (1,967,991 live births), with complete postnatal data for at least 6 years. We identified 363 patients (2792 patient-years of follow-up) who had received the Fontan procedure, giving an incidence of 0.184/1000 live births. RESULTS: The overall Fontan surgical survival rate was 81.8%. In post-Fontan patients, the 10-year survival was 0.822 (±0.026). Causes of death included cardiac (43.8%), infection (20.8%), out-of-hospital death (16.7%), sudden death (8.3%), cerebral vascular accident (8.3%) and malignancy (2.1%). The risk of unexpected death (sudden death and out-of-hospital death) was 4.0%, or 0.55% per post-Fontan patient-year. Arrhythmias were common (12.1%). Supraventricular tachycardia was the most common type of arrhythmia, and occurred prior to the Fontan procedure in 22 patients, with a cumulative risk of 2.2%, 6.3%, and 11.6% by the age of 1, 5 and 10 years, respectively. Arrhythmia intervention was performed in 40.9% of those with arrhythmia, including electrophysiological studies/ablation in 12 and device therapy in 6 patients. CONCLUSIONS: In conclusion, the incidence of Fontan patients was 0.184/1000 live births. Their medical complexity included a high risk of supraventricular tachycardia and unexpected death by adolescence.

Cumulative postnatal risk of pediatric sudden death and all-cause mortality in nationwide birth cohorts of Taiwan and the United States.

BACKGROUND: To investigate the cumulative postnatal risk of pediatric sudden death (SD) for each neonate and the temporal/regional differences which are still unclear. METHODS: We established a birth cohort (2000-2014) from our national database and obtained reference data about the United States (US) from the national website. RESULTS: Among 3,097,277 live births, we identified 1661 children with SD (56.8% male). The postnatal cumulative risk of SD was 0.35, 0.49, 0.56 and 0.59/1000 by age 0, 5, 11 and 14 years. Coexisting cardiac diagnosis was noted in 347 (20.9%) and non-cardiac diagnosis in 300 (18.1%) patients. Cumulative all-cause mortality was 5.3, 6.78, 7.63 and 8.06/1000 by age 0, 5, 11 and 14 years. Risks of SD and all-cause death decreased over birthyear. SD risk decreased particularly after the 2008 birthyear. Risks of SD and all-cause death were the highest in Eastern Taiwan, but SD/all-cause death ratio was high in Taipei metropolitan and Northern Taiwan. Cumulative risk of SD (0.54/1000 by age 14) and all-cause mortality (9.06/1000 by age 14) in the US decreased over time. African-Americans were at the highest risks of SD and all-cause mortality. However, American-Indians/Alaska-natives exhibited the highest SD/all-cause death ratio. CONCLUSION: This study provides the cumulative risk of SD (1 in 1694 newborns) by age 14 years. The time trend underlines the effect of medical advance and education on SD prevention. Distinct regional/ethnic differences in risks of SD and all-cause death in Taiwan and the US indicate the necessity of different strategies to diminish the disparity.

Shock and unresponsiveness to repeated courses of intravenous immunoglobulin in Kawasaki disease: a nationwide database study.

BACKGROUND: We aimed to investigate the clinical implications of unresponsiveness to single or repeated courses intravenous immunoglobulin (IVIG) and Kawasaki disease (KD) shock syndrome in patients with KD in an era of a single brand of IVIG. METHODS: Data were collected from National Health Insurance database 2010-2013. Characteristics of the KD patients were analyzed, including age, gender, shock, and associated coronary aneurysms. RESULTS: There were 3043 KD patients (male: 1872) identified. Among them, 46 (1.51%) had KDSS, 261 patients (8.5%) had IVIG unresponsiveness, and 225 patients (7.4%) developed coronary aneurysms. Moreover, 51 patients did not respond to the second course IVIG therapy, i.e., re-IVIG unresponsiveness. KDSS was associated with the occurrence of IVIG unresponsiveness (P < 10-4) and re-IVIG unresponsiveness (P = 0.02). In addition to male gender and KD shock syndrome, IVIG unresponsiveness (OR: 2.18, 95% CI: 1.48-3.22, P = 0.001) and re-IVIG unresponsiveness (OR: 2.87, 95% CI: 1.40-5.89, P = 0.004) were both independent risk factors for coronary aneurysms. CONCLUSIONS: In a nationwide KD cohort, both IVIG unresponsiveness and re-IVIG unresponsiveness increase the risk of coronary aneurysms. Such observation addresses the importance of refining the treatment for IVIG unresponsiveness, at least in those with KD shock syndrome.

Adult Congenital Heart Disease in a Nationwide Population 2000-2014: Epidemiological Trends, Arrhythmia, and Standardized Mortality Ratio.

BACKGROUND: The adult congenital heart disease (ACHD) population will grow with medical advances, but data are limited. We investigated the epidemiological profile of ACHD in Taiwan, a country with a congenital heart disease program since 1955, population of 23 million, and easily accessible high-standard medical care. METHODS AND RESULTS: ACHD patients, born after 1954, were identified from the nationwide database 2000-2014. The ACHD prevalence in the population aged 18 to 59 was 140.53, 157.08, 182.45, and 217.00 per 100 000 in 2000, 2005, 2010, and 2014, respectively (increasing time trend, P<0.0001). Percentage of severe ACHD also increased over time (P<0.0001) and was 11.70% in 2014. The 5 leading ACHD diagnoses were ventricular septal defect, secundum atrial septal defect, patent ductus arteriosus, pulmonary stenosis, and tetralogy of Fallot. Freedom from tachyarrhythmia at age 50 years was 0.574 and 0.710 for severe and simple ACHD, respectively. Cardiac causes accounted for the majority of deaths, followed by malignancy in simple ACHD and external causes/sudden death/out-of-hospital death in severe ACHD patients. The proportion of unexpected death was 10%. Compared with the general population, the standardized mortality ratio was higher not only in severe ACHD (3.164; 95% confidence interval, 2.664-3.664), but also in women with simple ACHD (1.704; 95% confidence interval, 1.499-1.909), with a higher proportion of cardiac, labor, and sudden death as causes of death. CONCLUSIONS: We demonstrated an increasing trend in ACHD prevalence and medical complexity. They are at risk of tachyarrhythmia, higher mortality, and unexpected deaths, suggesting a gap in their medical care.

Contemporary Postnatal Incidence of Acquiring Acute Myocarditis by Age 15 Years and the Outcomes From a Nationwide Birth Cohort.

OBJECTIVES: Acute myocarditis can be lethal, but the incidence remains unclear because of its wide manifestation spectrum. We investigated the postnatal incidence of acute myocarditis and risk factors for morbidity and mortality. DESIGN: Retrospective derived birth cohort study. SETTING: Taiwan National Health Insurance Database for the period 2000-2014. PATIENTS: Children born between 2000 and 2009 with complete postnatal medical care data for at least 5 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From among 2,150,590 live births, we identified 965 patients (54.8% male) admitted with the diagnosis of acute myocarditis, accounting for an overall incidence of 0.45/1,000. The cumulative incidence rates were 0.19/1,000, 0.38/1,000, 0.42/1,000, and 0.48/1,000 by ages 1, 5, 10, and 15 years, respectively. Male predominance was noted in infants and school age children (age group 6-14 yr). Arrhythmias, including tachyarrhythmia (4.8%) and bradyarrhythmia (1.1%), occurred in 56 patients. Extracorporeal membrane oxygenation support was provided to 62 patients (6.4%) and additional left ventricular assist devices in six of them. The mortality at discharge was 6.3%. The presence of ventricular tachyarrhythmia, bradyarrhythmia, and an onset at school age (6-14 yr) were associated with increased odds for the need for extracorporeal membrane oxygenation, which was the only predictor for mortality at discharge (hazard ratio, 7.85; 95% CI, 3.74-9.29). In patients who survived the acute myocarditis, late mortality was relatively low (36/904 = 4.0%). The overall survival of children with acute myocarditis were 90.9%, 90.3%, and 89.8% by the intervals of 1, 5, and 10 years after the myocarditis, respectively. CONCLUSIONS: This birth cohort study determined the cumulative incidence of acute myocarditis for neonates by 15 years old to be one in 2,105. In an era of extracorporeal membrane oxygenation, the need of extracorporeal membrane oxygenation may reflect the severity of acute myocarditis and predict its outcome.

Postnatal Risk of Acquiring Kawasaki Disease: A Nationwide Birth Cohort Database Study.

OBJECTIVE: To investigate the postnatal risk of Kawasaki disease and coronary complications from a nationwide birth cohort in Taiwan, a country with the third-highest incidence of Kawasaki disease worldwide. STUDY DESIGN: We enrolled children born between 2000 and 2009 with complete postnatal medical care records for 2000-2014 in the Taiwan national database. RESULTS: Out of a total of 2 150 590 live births, we identified 6690 (62.6% boys) patients with Kawasaki disease. The onset was mostly (93.9%) within the first 5 years of life (median, 16 months; 38% during infancy), but was rare within the first 3 months of life. The overall cumulative incidence of Kawasaki disease by age 5 years was 2.78‰ (3.33‰ for boys and 2.17‰ for girls; P < .001) and exhibited an increasing trend with birth year (from 2.28‰ for 2000 to 3.67‰ for 2009). The incidence ratio was 1.535 in boys and 1.055 in each increasing year. Kawasaki disease recurred more often in younger patients (cumulative incidence, 2.3% in infants vs 1.7% in children aged 1-4 years). Coronary complications occurred in 16.2% of the patients, including 4 cases of acute myocardial infarction (3 occuring during the acute stage and 1 occurring 5 years later). The probability of a major cardiac event (infarction, undergoing percutaneous coronary intervention or coronary artery bypass grafting, or death) by adolescence was 1.9%. CONCLUSIONS: The postnatal risk of Kawasaki disease was 3‰-4‰ and increased with every birth year. Patients with Kawasaki disease are at substantial risk for a major cardiac events during childhood.

Association of a Bundled-Payment Program With Cost and Outcomes in Full-Cycle Breast Cancer Care.

IMPORTANCE: Value-driven payment system reform is a potential tool for aligning economic incentives with the improvement of quality and efficiency of health care and containment of cost. Such a payment system has not been researched satisfactorily in full-cycle cancer care. OBJECTIVE: To examine the association of outcomes and medical expenditures with a bundled-payment pay-for-performance program for breast cancer in Taiwan compared with a fee-for-service (FFS) program. DESIGN, SETTING, AND PARTICIPANTS: Data were obtained from the Taiwan Cancer Database, National Health Insurance Claims Data, the National Death Registry, and the bundled-payment enrollment file. Women with newly diagnosed breast cancer and a documented first cancer treatment from January 1, 2004, to December 31, 2008, were selected from the Taiwan Cancer Database and followed up for 5 years, with the last follow-up data available on December 31, 2013. Patients in the bundled-payment program were matched at a ratio of 1:3 with control individuals in an FFS program using a propensity score method. The final sample of 17 940 patients included 4485 (25%) in the bundled-payment group and 13 455 (75%) in the FFS group. MAIN OUTCOMES AND MEASURES: Rates of adherence to quality indicators, survival rates, and medical payments (excluding bonuses paid in the bundled-payment group). The Kaplan-Meier method was used to calculate 5-year overall and event-free survival rates by cancer stage, and the Cox proportional hazards regression model was used to examine the effect of the bundled-payment program on overall and event-free survival. Sensitivity analysis for bonus payments in the bundled-payment group was also performed. RESULTS: The study population included 17 940 women (mean [SD] age, 52.2 [10.3] years). In the bundled-payment group, 1473 of 4215 patients (34.9%) with applicable quality indicators had full (100%) adherence to quality indicators compared with 3438 of 12 506 patients (27.5%) with applicable quality indicators in the FFS group (P < .001). The 5-year event-free survival rates for patients with stages 0 to III breast cancer were 84.48% for the bundled-payment group and 80.88% for the FFS group (P < .01). Although the 5-year medical payments of the bundled-payment group remained stable, the cumulative medical payments for the FFS group steadily increased from $16 000 to $19 230 and exceeded pay-for-performance bundled payments starting in 2008. CONCLUSIONS AND RELEVANCE: In Taiwan, compared with the regular FFS program, bundled payment may lead to better adherence to quality indicators, better outcomes, and more effective cost-control over time.

Ventricular Fibrillation in a General Population　- A National Database Study.

BACKGROUND: Ventricular fibrillation (VF) is a life-threatening disease that can be remedied by prompt defibrillation. However, data regarding such risk in a general population remain limited. This general population study was to explore the epidemiological profile of VF.Methods and Results:We investigated patients with VF younger than 60 years (average population, 19,725,031) using a national database spanning the period 2000-2010. We identified 3,971 (68.4% male) patients with VF (crude incidence rate: 1.83/100,000). Incidence rates were low in patients younger than 10 years and increased steadily after adolescence. Comorbidities were noted in 2,766 (69.7%) patients, with 2,431 (61%) having cardiac diseases. Over half of the adolescent and young adult patients did not have comorbidities. Among the 838 deaths (mortality rate 21.1%), approximately half (381/838, 45.5%) occurred after arrival at emergency services (ES). The proportion of deaths after arrival at ES relative to total deaths increased sharply to a peak in the 15-19-years age group and thereafter remained stationary. CONCLUSIONS: VF patients, with a male dominance, increased after adolescence and were likely to die at presentation to ES. Approximately half of young adults, with high mortality, did not have comorbidities, suggesting underdiagnosis of underlying primary electrical diseases and the need for implementing automated external defibrillator programs. (Circ J 2016; 80: 2310-2316).

Postnatal cumulative incidence of supraventricular tachycardia in a general pediatric population: A national birth cohort database study.

BACKGROUND: Supraventricular tachycardia (SVT) is a common pediatric tachycardia, but the true incidence is unknown. OBJECTIVE: We sought to investigate the true postnatal incidence and its medical needs. METHODS: We derived a birth cohort comprised children born between 2000 and 2008 who had complete postnatal medical data in the Taiwan National Health Insurance Database for the period from 2000 to 2014. RESULTS: From 1,967,911 live births, we identified 2021 patients with SVT (51.6% men), accounting for an overall incidence of 1.03 per 1000 patient-years (Wolff-Parkinson-White syndrome accounted for 16.2%). The cumulative incidence was 0.06, 0.25, 0.45, 0.88, and 1.39 per 1000 patient-years by the age of 1 month, 1 year, 5 years, 10 years, and 15 years, respectively. Major congenital heart disease (5.3%; hazard ratio 6.66; 95% confidence interval 2.98-14.87) and cardiomyopathy (0.9%; hazard ratio 8.78; 95% confidence interval 3.39-22.78) were associated with mortality. In patients without major congenital heart disease, the cumulative incidence of SVT was 0.05, 0.22, 0.41, 0.84, and 1.33 per 1000 patient-years by the age of 1 month, 1 year, 5 years, 10 years, and 15 years, respectively. By the age of 15 years, the annual risk of death and sudden death was 0.13% and 0.01% per patient-year, respectively. Radiofrequency catheter ablation was performed in 173 patients at the median age of 11 years: 1.7% during infancy, 5.8% by the age of 5 years, and 31.8% by the age of 10 years. The probability of being free from receiving ablation by the age of 15 years was 83.4%. CONCLUSION: This birth cohort study provides the true incidence of pediatric SVT and indicates that almost one-fifth of the patients with SVT have already received ablation in the pediatric ages.

Risk of Respiratory Syncytial Virus Infection in Cyanotic Congenital Heart Disease in a Subtropical Area.

OBJECTIVE: To compare the risk of respiratory syncytial virus (RSV)-associated hospitalization and analyze the epidemiology of RSV infection in patients with cyanotic and acyanotic congenital heart disease (CHD), we analyzed the nationwide health insurance database from 2005-2010. STUDY DESIGN: This study included 1050 patients with cyanotic CHD and 7077 patients with acyanotic CHD. Patients with acyanotic CHD were further classified into hemodynamically significant (hs)-acyanotic and non-hs-acyanotic groups according to whether they underwent surgery or took at least 2 anticongestive medications. RESULTS: RSV-associated hospitalization was higher in the cyanotic group than in hs-acyanotic and non-hs-acyanotic groups both before 1 year of age (4.8% vs 2.1% vs 1.5%, P < .001) and between 1 and 2 years of age (0.9% vs 0.56% vs 0.14%, P = .003). The hospitalization duration, intensive care, ventilator support prevalence, hospitalization cost, and mortality rate were significantly higher in the cyanotic group than in the other 2 groups. Logistic regression revealed that cyanotic CHD was the most significant risk factor for the ventilator support and RSV-associated mortality. In both patients with cyanotic and acyanotic CHD, RSV-associated hospitalization rate was higher in patients aged younger than 1 year and in spring and autumn in Taiwan, a subtropical country. CONCLUSIONS: The results show that patients with cyanotic CHD have a higher risk of severe RSV infection than do those with acyanotic CHD. RSV prophylaxis is more important and may reduce costs more for patients with cyanotic CHD.

Paradigm shift in the intervention for secundum atrial septal defect in an era of transcatheter closure: A national birth cohort study.

BACKGROUND: Secundum atrial septal defect (ASDII) is a common congenital heart defect, but the intervention, either transcatheter or surgical, needs are unclear. This study was to examine the paradigm shift in its intervention in an era of transcatheter closure. METHODS AND RESULTS: The study birth cohort 2000-2008 (2,070,145 live births) with complete postnatal medical data was derived from the national database (2000-2014) of Taiwan, a country with national health insurance and easily accessible high-standard medical care. We found 5,515 patients with simple ASDII (median follow-up 12.2 years, one-third diagnosed after age 6 years, incidence 2.66/1,000 live births). Excluding patients with coexisting ventricular septal defect, ASDII intervention was performed in 1,435 of 4,585 patients: transcatheter closure in 1,080 (23.6%) and surgery in 355 (7.8%). The interventional need is 0.69 per 1,000 live births: 0.52 per 1,000 for transcatheter closure and 0.17 per 1,000 for surgery. In the era of transcatheter closure (July 2004-December 2014), ASDII intervention increased to 3.56-fold, but the number of operations decreased to half. The freedom from intervention was lower, and the age at intervention was younger (freedom from intervention at age 6 years, 0.749 vs 0.805, P < .001). In patients born in the era of transcatheter closure, 19.5% (108/555) of the intervention was surgery. Atrioventricular block occurred in 1.12% of those patients after transcatheter closure and none after surgery (P = .149). CONCLUSIONS: In the era of catheter intervention, the interventional criteria for ASDII are less strict and one-third of the patients may receive intervention, mostly transcatheter closure, at the pediatric ages.

Risk of Systemic Hypertension and Cerebrovascular Accident in Patients With Aortic Coarctation Aged <60 Years (from a National Database Study).

Patients with coarctation of the aorta (CoA) may develop hypertension and cerebrovascular accident (CVA) late after intervention, but the risk is still unclear. Therefore, we studied the epidemiologic profile from a general population aged <60 years to assess the relative risk. Our study population consisted of 126,943 patients with congenital heart disease (CHD) derived from Taiwan's National Health Insurance database from 2000 to 2010 (population 22,765,535). There were 2,295 patients with CoA (50.3% men) (prevalence: 0.116/1000). Associated cardiac lesions in 44% of the patients with CoA included ventricular septal defect (VSD; 23.3%), patent ductus arteriosus (7.5%), atrial septal defect (9.0%), and so forth. Hypertension occurred in 190 patients (8.3%) and was related to age, without associated VSD (odds ratio [OR] 5.90, 95% confidence interval [CI] 2.12 to 16.39, p = 0.001) and male gender (OR 1.59, 95% CI 1.09 to 2.30, p = 0.015). The incidence of hypertension increased rapidly in the young adulthood and was 1.36% in pediatric age group and 28.9% and 45.7% in age group 20 to 29 and 30 to 39, respectively. CVA occurred in 29 patients (1.67%), and the coexisting hypertension was the single predictor (OR 3.19, 95% CI 1.13 to 9.00, p = 0.029). Furthermore, in all patients with CHD, CoA was an independent risk factor for hypertension (OR 15.65, 95% CI 12.44 to 19.68, p <0.001) and CVA (OR 6.55, 95% CI 4.41 to 9.74, p <0.001). Comparing with non-CoA CHD patients, patients with CoA, particularly men, adult, and patients without VSD, have high risk of hypertension, which would further increase the risk of CVA. Early recognition and timely intervention for the hypertension in patients with CoA is mandatory.

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.

Nucleos(t)ide analogues associated with a reduced risk of hepatocellular carcinoma in hepatitis B patients: a population-based cohort study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major complication of hepatitis B virus (HBV) infection. This study investigated the association between nucleos(t)ide analogue (NA) use and the risk of HCC and mortality in HBV carriers on the basis of the Taiwan National Health Insurance Database. METHODS: In all, 1544 HBV carriers taking NAs (treated cohort) who were identified between October 1, 2003 and December 31, 2011 were examined for their risk of HCC and mortality; 1544 patients not receiving NA treatment (untreated cohort) were selected via propensity score matching as the comparison group. The risks of first tumor occurrence and mortality were compared. RESULTS: The treated cohort had a significantly lower HCC occurrence rate (6.0%; 95% confidence interval [CI], 4.4%-7.9%) in comparison with the untreated cohort (8.5%; 95% CI, 6.6%-10.6%; P = .0025). The overall mortality rates for the treated and untreated cohorts were 6.9% (95% CI, 5.3%-8.7%) and 9.4% (95% CI, 7.7%-11.3%), respectively (P = .0003). After adjustments for competing confounders, Cox regression analyses showed that NA use significantly reduced the risk of HCC (hazard ratio [HR], 0.64; 95% CI, 0.45-0.93; P = .017) and overall mortality (HR, 0.58; 95% CI, 0.43-0.79; P < .001). There was a dose-response relationship between NA use and the risk of HCC in the treated cohort. With respect to no NA use, the adjusted HRs were 0.93 (95% CI, 0.58-1.48), 0.67 (95% CI, 0.42-1.06), and 0.35 (95% CI, 0.17-0.70) for 90 to 365, 366 to 730, and >730 cumulative defined daily doses of NAs, respectively. CONCLUSIONS: NA use reduced the risk of HCC and overall mortality in HBV carriers.