Survival outcomes for congenital heart disease from Southern Malaysia: results from a congenital heart disease registry.

OBJECTIVE: Limited population-based studies are available on the survival of congenital heart disease (CHD) from lower- and middle-income countries. Therefore, we evaluated the survival from birth until 15 years and associated factors for mortality. METHODS: This population-based cohort study included all children with CHD registered in the Pediatric Cardiology Clinical Information System born between 2006 and 2020 in Johor, Malaysia. The mortality rate was calculated, and Cox proportional hazard regression analysis was used to determine factors associated with mortality. The Kaplan-Meier analysis was used to estimate the survival rates at 1, 5, 10 and 15 years. RESULTS: There were 5728 patients with CHD studied, with 1543 (27%) lesions resolved spontaneously, 322 (5.6%) were treated with comfort care, 1189 (21%) required no intervention, and 2674 (47%) needed surgery or intervention. The overall mortality rate was 15%, with a median age of death of 3.7 months (IQR 0.9-9.8 months). Preoperative/intervention death was observed in 300 (11%), and 68 (3.2%) children died within 30 days of surgery or intervention. The overall estimated survival at 1, 5, 10 and 15 years was 88%, 85%, 84% and 83%, respectively. The independent factors associated with mortality were male gender, associated syndrome or extra-cardiac defect, pulmonary hypertension, antenatal diagnosis and severe lesions. CONCLUSIONS: Eight out of 10 patients with CHDs survived up to 15 years of age. However, 10% of CHDs who require intervention die before the procedure. Thus, improving congenital cardiac surgery and enhancing the overall healthcare system are crucial to improve survival.

The Incidence and Factors Associated with the Recurrence of Supraventricular Tachycardia in Children: 15 Years Experience from Middle-Income Country.

Limited data are available concerning supraventricular tachycardia (SVT) recurrence. Hence, this study aimed to determine the incidence, outcome, and factors associated with SVT recurrence. This retrospective, observational, population-based study was conducted among children with SVT from 2006 to 2020. The primary outcome measure was SVT recurrence. Kaplan Meier analysis was used to estimate SVT-free at 1, 5, and 10 years after diagnosis. Cox regression analysis was used to identify independent factors associated with recurrence. There were 156 patients with SVT with a median age at diagnosis of 1.9 years (Interquartile range [IQR] 11 days to 8.7 years) and follow-up for a median of 3.5 years (IQR 1.7 to 6.1 years). 35 patients (22%) had recurrent SVT at a median age of 7.8 years (IQR 4.4 to 12 years). Infants with Wolff-Parkinson-White Syndrome (WPW) had the highest recurrence (11/16, 68%), with 33% SVT-free at 5 years follow-up. The lowest recurrence rate was observed in neonatal diagnosis (2/54, 3.7%) with 98% SVT-free at 5 years follow-up. The independent factors associated with the recurrence of SVT were the diagnosis of WPW with an adjusted hazard ratio (aHR) of 5.2 (95% CI 2.4-11.2), age of more than 1 year at diagnosis (aHR 3.7 95% CI 1.4-9.7), and combine with or need second-line therapy (aHR 4.0 95% CI 1.5-10.7). One in five children with SVT experienced a recurrence, which is more likely for those with WPW, multiple maintenance therapy, and older age at first presentation. Whereas neonates with non-WPW may benefit from shorter maintenance therapy.

Survival and outcomes of isolated neonatal ventricular septal defects: A population-based study from a middle-income country.

Background and Aims: Limited data on the survival and outcomes of ventricular septal defect (VSD) in middle-income countries are available. Hence, this study aims to determine the survival and factors associated with mortality among neonatal VSD. Materials and Methods: This is a retrospective, population based study of neonates with isolated VSD born between 2009 and 2019. Kaplan-Meier analysis was used to estimate the overall survival. Cox regression analysis was used to determine factors associated with mortality. Results: There were 726 patients studied, with 82 (11%) of them having trisomy 21. The median age of diagnosis and follow-up was 5 days (interquartile range [IQR]: 2-10 days) and 2.3 years (IQR: 0.6-4.8 years), respectively. Of 726, 399 (55%) were perimembranous, 218 (30%) muscular, and 109 (15%) outlet VSD. VSD was small in 309 (42%), moderate in 337 (46%), and large in 80 (11%). Of 726 patients, 189 (26%) had congestive heart failure (CHF) and 52 (7.2%) developed pulmonary hypertension (PHT). Interestingly, one-third of CHF and PHT resolved over time during follow-up. Only 1 (0.1%) patient had infective endocarditis, 38 (5.2%) developed aortic regurgitation, and none had Eisenmenger syndrome. Overall, 149 (20%) needed surgery, 399 (55%) spontaneously closed, and 178 (25%) remained small. The mortality rate was 3.9% (28), 16 (57%) preoperatively, and 11 (39%) due to pneumonia. Trisomy 21, PHT, and birth weight <2.5 kg were independent factors for mortality with an adjusted hazard ratio of 6.0 (95% confidence interval [CI]: 2.1-16.9), 3.2 (95% CI: 1.2-8.4), and 3.6 (95% CI: 1.7-7.8), respectively. The overall survival at 1, 5, and 10 years was 96% (95% CI: 95-98), 95% (95% CI: 94-97), and 95% (95% CI: 94-97), respectively. Conclusions: Despite limited pediatric and congenital cardiac services in middle-income countries, the overall survival of neonatal VSD is good, with poor outcomes in small infants, PHT, and trisomy 21.

Delayed diagnosis of Kawasaki disease in Malaysia: Who is at risk and what is the outcome.

BACKGROUND: Data on the delayed diagnosis of (KD) is limited. This study aimed to determine the prevalence and trend of delayed diagnosis over time and identify the associated risk factors in Malaysia. METHODS: This retrospective, observational, population-based study involved all children with KD registered in Johor Kawasaki Clinical Registry over 10 years (January 2010 and December 2019). The prevalence of delayed diagnosis and its trend over time was calculated. Multivariable binary logistic regression was used to identify the independent risk factors for delayed diagnosis. RESULTS: There were 556 cases of KD, with 28% having incomplete criteria, 11% atypical presentation, while 10% developed a coronary aneurysm. The overall prevalence of delayed diagnosis was 9.9% (95% confidence interval (CI): 7.6-12.7%). There was a statistically significant decrease in delayed diagnosis over time (P = 0.008), with the latest rate of 4.6%. The majority of delayed diagnoses were due to failure to diagnose the disease during the initial consultation. Independent risk factors for delayed diagnosis were children older than 1 year, diagnosis before 2015, atypical presentation, and incomplete KD, with adjusted odds ratios (ORs) of 2.7, 2.3, 4.3, and 3.6, respectively. Compared to early diagnosis of KD, delayed diagnosis was significantly associated with coronary aneurysms (27.3% vs. 8.2%, P < 0.001, OR 4.2, [95% CI: 2.1-8.3]). CONCLUSIONS: One-tenth of cases of KD were diagnosed late, but it has improved over time. Children > 1 year, presenting with atypical presentation, and incomplete criteria are associated with late diagnosis.

Epidemiology, clinical characteristics, and immediate outcome of Kawasaki disease: a population-based study from a tropical country.

Data on Kawasaki disease from tropical countries are scarce. Hence, this population-based study aims to determine the epidemiology, clinical characteristics, and outcome of Kawasaki disease in children enrolled in the Kawasaki disease registry between 2006 and 2019 in Southern Malaysia. Diagnosis of Kawasaki disease was made using standard criteria. Primary outcome measure was a coronary artery aneurysm. Multivariable logistic regression was used to analyze the associated risk factors for coronary artery aneurysm. There were 661 Kawasaki disease, with 27% incomplete and 11% atypical presentations. Male-to-female ratio was 2:1, and median age of diagnosis was 1.4 years (interquartile range 9 to 32 months). Incidence in children of less than 5 years was 14.8 (95% confidence interval [CI]: 13.6 to 16.0) per 100,000 population, higher in males (19/100,000) and Chinese (22/100,000), with a gradual increase from 5.7/100,000 in 2006 to 19.6/100,000 in 2019, p < 0.001. Incidence in children between 5 and 9 years old was 1.3 (95% CI: 0.9 to 1.6) per 100,000 population and remained stable over time. There was a seasonal pattern with peak incidence during the rainy season. Out of 625 intravenous immunoglobulins (IVIG)-treated Kawasaki disease, 7.4% were resistant, and 9% had coronary artery aneurysms. Atypical presentation, male sex, late diagnosis, and IVIG resistance were independent risk factors for coronary artery aneurysms.Conclusions: Despite the tropical climate, Kawasaki disease epidemiology is similar to non-tropic regions with seasonal patterns and a rising incidence. Atypical presentation, male sex, late diagnosis, and IVIG resistance were significantly associated with coronary artery aneurysms. What is Known: • Kawasaki disease predominantly occurs in males, children less than 5 years old, and the Asian population. • Male sex, late diagnosis, incomplete Kawasaki disease, and IVIG resistance were associated with coronary artery aneurysms. What is New: • In multi-ethnic Asian countries such as Malaysia, ethnic Chinese have a higher prevalence of Kawasaki disease compared to other ethnicities. • Kawasaki disease with atypical presentation can occur in both complete and incomplete Kawasaki disease and is significantly associated with a coronary artery aneurysm.

Survival and associated risk factors for mortality among infants with persistent pulmonary hypertension of the newborn in Malaysia.

OBJECTIVE: This study aims to determine the immediate outcome of persistent pulmonary hypertension of the newborn (PPHN) and risk factors for mortality in the era of inhaled nitric oxide (iNO). STUDY DESIGN: This observational cross-sectional study includes 195 confirmed PPHN with a gestational age of ≥34 weeks without congenital heart disease. Multivariable logistic regression was used to identify risk factors for mortality. RESULTS: The mortality rate was 16.4%, with the highest mortality with pulmonary hypoplasia. Of 195, 65% received iNO; 18% were iNO non-responders with the majority having pulmonary hypoplasia. Independent risk factors for mortality were the presence of reversal of flow at the descending aorta, pulmonary hypoplasia, APGAR scores ≤ 5 at 5 min, and idiopathic PPHN with an adjusted odds ratio of 15.9, 7.5, 6.7, and 6.4, respectively. CONCLUSIONS: Despite the usage of iNO, mortality due to PPHN remains high and is related to etiology and cardiac function.

Birth prevalence and late diagnosis of critical congenital heart disease: A population-based study from a middle-income country.

AIMS: There are limited data regarding critical congenital heart disease (CCHD) from middle-income countries (MIC). This study aims to determine the birth prevalence, rate of late diagnosis, and influence of timing of diagnosis on the outcome of CCHD. SETTING AND DESIGN: Retrospective observational cohort study in the State of Johor, Malaysia. SUBJECTS AND METHODS: All infants born between January 2006 and December 2015 with a diagnosis of CCHD, defined as infants with duct-dependent lesions or cyanotic heart disease who may die without early intervention. The late diagnosis was defined as a diagnosis of CCHD after 3 days of age. RESULTS: Congenital heart disease was diagnosed in 3557 of 531,904 live-born infants and were critical in 668 (18.7%). Of 668, 347 (52%) had duct-dependent pulmonary circulation. The birth prevalence of CCHD was 1.26 (95% confidence interval: 1.16-1.35) per 1000 live births, with no significant increase over time. The median age of diagnosis was 4 days (Q1 1, Q3 26), with 61 (9.1%) detected prenatally, and 342 (51.2%) detected late. The highest rate of late diagnosis was observed in coarctation of the aorta with a rate of 74%. Trend analysis shows a statistically significant reduction of late diagnosis and a significant increase in prenatal detection. However, Cox regression analysis shows the timing of diagnosis does not affect the outcome of CCHD. CONCLUSIONS: Due to limited resources in the MIC, the late diagnosis of CCHD is high but does not affect the outcome. Nevertheless, the timing of diagnosis has improved over time.

The birth prevalence, severity, and temporal trends of congenital heart disease in the middle-income country: A population-based study.

OBJECTIVES: There is limited data on congenital heart disease (CHD) from the lower- and middle-income country. We aim to study the epidemiology of CHD with the specific objective to estimate the birth prevalence, severity, and its trend over time. DESIGN: A population-based study with data retrieved from the Pediatric Cardiology Clinical Information System, a clinical registry of acquired and congenital heart disease for children. SETTING: State of Johor, Malaysia. PATIENTS: All children (0-12 years of age) born in the state of Johor between January 2006 and December 2015. INTERVENTION: None. OUTCOME MEASURE: The birth prevalence, severity, and temporal trend over time. RESULTS: There were 531,904 live births during the study period with 3557 new cases of CHD detected. Therefore, the birth prevalence of CHD was 6.7 per 1000 live births (LB) (95% confidence interval [CI]: 6.5-6.9). Of these, 38% were severe, 15% moderate, and 47% mild lesions. Hence, the birth prevalence of mild, moderate, and severe CHD was 3.2 (95% CI: 3.0-3.3), 0.9 (95% CI: 0.9- 1.1), and 2.6 (95% CI: 2.4-2.7) per 1000 LB, respectively. There was a significant increase in the birth prevalence of CHD, from 5.1/1000 LB in 2006 to 7.8/1000 LB in 2015 (P < .0001) due to increase in detection of both mild (1.9/1000 LB in 2006 to 3.9/1000 LB in 2015, P < .001) and severe CHD (1.8/1000 LB in 2005 to 2.9/1000 LB in 2015, P < .001). CONCLUSIONS: The birth prevalence of CHD was 6.7 per 1000 live births, and two in five were severe and significantly associated with syndrome and extracardiac defect. There was a significant increase in the detection of severe lesions in recent years leading to more burden to resources that are already limited in the middle-income country. Therefore, strategic and comprehensive pediatric and congenital heart surgery program is required.

Survival and Associated Risk Factors for Mortality Among Infants with Critical Congenital Heart Disease in a Developing Country.

Critical congenital heart disease (CCHD) is associated with significant morbidity and mortality. However, data on survival of CCHD and the risk factors associated with its mortality are limited. This study examined CCHD survival and the risk factors for CCHD mortality. Using a retrospective cohort study of infants born with CCHD from 2006 to 2015, survival over 10 years was estimated using Kaplan-Meier analysis, and the risk factors for mortality were analyzed using multivariate Cox proportional hazards regression. A total of 491 CCHD cases were included in the study, with an overall mortality rate of 34.8% (95% confidence interval [CI] 30.6-39.2). The intervention/surgical mortality rate was 9.8% ≤ 30 days and 11.5% > 30 days after surgery, and 17% died before surgery or intervention. The median age at death was 2.7 months [first quartile: 1 month, third quartile: 7.3 months]. The CCHD survival rate was 90.4% (95% CI 89-91.8%) at 1 month, 69.3% (95% CI 67.2-71.4%) at 1 year, 63.4% (95% CI 61.1-65.7%) at 5 years, and 61.4% (95% CI 58.9-63.9%) at 10 years. Weight of < 2 kg at diagnosis, associated syndromes, poor pre-operative condition, and non-duct-dependent CCHD were independent risk factors for poor survival, with hazard ratios of 2.61, 2.10, 2.22, and 1.70, respectively. CCHD is associated with a high mortality rate. Low weight, poor pre-operative condition, associated syndromes, and non-duct-dependent CCHD are significant risk factors affecting the survival of infants with CCHD.