Ming-Tai Lin

Losartan Added to β-Blockade Therapy for Aortic Root Dilation in Marfan Syndrome: A Randomized, Open-Label Pilot Study

OBJECTIVE To assess the tolerability and efficacy of the investigational use of the angiotensin II receptor blocker losartan added to β-blockade (BB) to prevent progressive aortic root dilation in patients with Marfan syndrome (MFS). PATIENTS AND METHODS Between May 1, 2007, and September 31, 2011, 28 patients with MFS (11 males [39%]; mean ± SD age, 13.1±6.3 years) with recognized aortic root dilation (z score >2.0) and receiving BB (atenolol or propranolol) treatment were enrolled. They were randomized to receive BB (BB: 13 patients) or β-blockade and losartan (BB-L: 15 patients) for 35 months. RESULTS In the BB-L group, aortic root dilation was reduced with treatment, and the annual dilation rate of the aortic root was significantly lower than that of the BB group (0.10 mm/yr vs 0.89 mm/yr; P=.02). The absolute aortic diameters at the sinus of Valsalva, annulus, and sinotubular junction showed similar trends, with a reduced rate of dilation in the BB-L group (P=.02, P=.03, and P=.03, respectively). Five patients (33%) treated with BB-L were noted to have a reduced aortic root diameter. However, the differences between the groups regarding changes in aortic stiffness and cross-sectional compliance were not statistically significant. CONCLUSION This randomized, open-label, active controlled trial mostly based on a pediatric population demonstrated for the first time that losartan add-on BB therapy is safe and provides more effective protection to slow the progression of aortic root dilation than does BB treatment alone in patients with MFS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00651235.

Transcatheter closure of moderate to large patent ductus arteriosus with the Amplatzer duct occluder

To investigate the acute and follow‐up results of transcatheter closure of moderate to large patent ductus arteriosus (PDA) with the Amplatzer duct occluder.

Reversal of Cardiac Dysfunction after Enzyme Replacement in Patients with Infantile-Onset Pompe Disease

OBJECTIVE To compare the effects of enzyme replacement therapy (ERT) on cardiac performance in symptomatic and symptom-free infants with Pompe disease. STUDY DESIGN Patients diagnosed between 1983 and 2008 were identified. Before the initiation of ERT, systolic dysfunction appeared only in patients > or = 5 months; thus we used this cut-point in age to divide clinically symptomatic patients into early and late treatment groups (Clin-E and Clin-L). Newborn screening (NBS) identified symptom-free patients. RESULTS Among a total of 40 patients, 14 received ERT: 5 in the Clin-L, 4 in the Clin-E, and 5 in the NBS groups. All patients showed cardiomegaly, hypertrophic myocardium, and elevated B-type natriuretic peptide (measured in the Clin-E and NBS groups). ERT improved the survival and outcomes. Regressed myocardial hypertrophy and lowered B-type natriuretic peptide level occurred after 1 to 6 months of ERT. Nonetheless, there were 2 deaths and 2 survivors requiring ventilator support in the Clin-L group. Despite the regressed QRS voltage and shortened QT dispersion, life-threatening arrhythmias were still observed in 3, but none in the NBS group. CONCLUSION ERT may restore the cardiac function in both symptomatic and symptom-free patients, but the beneficial effect may be unpredictable if given after the age of 5 months.

Clinical Implication of the C Allele of the ITPKC Gene SNP rs28493229 in Kawasaki Disease: Association With Disease Susceptibility and BCG Scar Reactivation.

Background: A functional single nucleotide polymorphism (SNP) (rs28493229) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene has been linked to the susceptibility to Kawasaki disease (KD). The implication remains unclear. Subjects and Methods: Genotyping for the ITPKC polymorphism was conducted on 280 unrelated Taiwanese children with KD and 492 healthy ethnically and gender-matched controls. The clinical manifestations and laboratory data were systemically collected. Results: The GC and CC genotypes of ITPKC gene SNP rs28493229 were overrepresented in KD patients (GG:GC:CC was 236:43:1, C allele frequency: 8.04%) than those in the controls (GG:GC:CC was 454:37:1, C allele frequency: 3.96%; OR: 2.23, P = 0.001). In KD patients, those with GC or CC genotypes of SNP rs28493229 (19/44) were more likely to have reactivation at the Bacille Calmette-Guérin (BCG) inoculation site than those with GG genotypes (66/236; OR: 1.96, P = 0.044). Such association was particularly strong in patients aged <20 months (OR: 3.26, P = 0.017). The other clinical manifestations were not related to this SNP. There were 160 (57.1%) patients with coronary arterial lesions. The development and the severity of coronary arterial lesion were also not associated with this SNP. Comparison between patients with and without BCG reactivation revealed only one difference: patients with reactivation were younger. Conclusion: In a cohort from a population with the worlds third highest incidence of KD, we demonstrated that the C-allele of ITPKC SNP rs28493229 is associated with KD susceptibility and BCG scar reactivation during the acute phase, although its frequency is lower than that in the Japanese cohort (22.6%), suggesting this SNP contributes to KD susceptibility through induced hyperimmune function reflected in the BCG reactivation.

Quality of life in adults with congenital heart disease: biopsychosocial determinants and sex-related differences

Objectives To assess the quality of life (QoL) in adults with congenital heart disease (ACHD) and to explore the sex-related differences and biopsychosocial determinants in an Asian cohort. Design Prospective cross-sectional clinical study. Setting One tertiary medical centre in Taiwan. Patients and methods The QoL of ACHD (≥20 years) was investigated using the Taiwanese version of the QoL questionnaire designed by the WHO, which assesses four domains of QoL (physical, psychological, social and environmental). Personality, psychological distress and family support were assessed using the Maudsley Personality Inventory, Brief Symptom Rating Scale, and the Family APGAR score, respectively. Results A total of 289 patients (age 33.2±10.6 years; 36% men) were studied. ACHD women had significantly lower QoL scores in the physical and psychological domains compared to the age-matched general population, whereas no differences were observed between ACHD men and the general population. Multivariate analysis showed that female gender was associated with poorer physical QoL; the sex difference in the psychological QoL was mediated by psychological distress. Interaction analysis showed that the effect of family support on the psychological domain of QoL may be different by sex. The determinants of QoL varied between different domains. Extroversion personality trait, psychological distress and family support were common determinants of most domains of QoL. Conclusions In ACHD, female gender was associated with poor physical and psychological QoL. The common denominators for QoL were primarily personality trait, psychological distress and family support, but not disease severity.

Transcatheter closure of atrial septal defect without balloon sizing.

Objective: To evaluate the safety and feasibility of transcatheter closure of atrial septal defect (ASD) without balloon sizing. Methods: A total of 243 patients (group I), aged 2.1–76 years (median 22 years), underwent transcatheter closure of ASD without balloon sizing. The maximal diameter of the defect was measured on transesophageal echocardiographic (TEE) images. The size of device selected was generally 4–6 mm and 5–8 mm larger than the maximal diameter, if the defect was <14 mm and ≥14 mm, respectively. The results of ASD closure in group I were compared with those of 271 patients (group II, median age 11 years) who underwent ASD closure with balloon sizing prior to the study period. Results: Of the 243 patients in group I, the maximal defect diameter ranged from 5.2 to 37 mm (mean 17.5 ± 6.6 mm, median 17 mm). A total of 247 Amplatzer septal occluders were deployed in 240 patients. Two patients were found to develop distal embolization of a device the next day. Therefore, failure occurred in five patients. Comparing the results between group I and group II, there was no significant difference in success rate (238/243 vs. 263/271), incidence of embolization (2/243 vs. 2/271) and complete closure rate at 3‐month follow‐up (94.1% vs. 95.8%). There is significant difference in mean age (26.6 ± 20.2 vs. 19.1 ± 17.6), maximal defect diameter (17.5 ± 6.6 vs. 14.1 ± 5.9 mm) and Qp/Qs ratio (2.77 ± 1.11 vs. 2.48 ± 0.97) between group I and II. The mean diameter of device used was significantly larger in group I than in group II (23.1 ± 8.1 vs. 19.6 ± 7 mm, P < 0.001). Conclusions: Balloon sizing may not be necessary in transcatheter closure of ASD.

Acute and late coronary outcomes in 1073 patients with Kawasaki disease with and without intravenous γ-immunoglobulin therapy

Objective To explore acute and late coronary outcomes and their risk/modifiers in patients with Kawasaki disease (KD). Design Retrospective study. Setting and patients 1073 patients with KD identified from a tertiary care medical centre (1980–2012; 8677 patient-years). Main outcome measures The acute coronary severities and late outcomes (survival free of coronary aneurysm persistence and ischaemia) were assessed. Results Coronary arterial lesions occurred in 40.6% of cases at their acute febrile stages, and persisted beyond 1 month in 196 (18.3%, M/F=138/58) patients: 125 (11.6%) had small aneurysms, 44 (4.1%) had medium aneurysms, and 27 (2.5%) had giant aneurysms. At follow-up (1–46 years), coronary aneurysms persisted in all with giant aneurysms, in 55% of those with medium aneurysms (18% with stenosis), and in 9% of those with small aneurysms. Ischaemia events occurred in 14 patients (M/F=13/1) and caused four deaths. Among the patients with KD with coronary aneurysms, 10-year ischaemia event-free and aneurysm persistence probability was 87.5% and 20.6%, respectively. The only independent risk for aneurysm persistence was the aneurysm severity 1 month after KD onset (χ2=80.73, p<10−3). Male patients and intravenous γ-immunoglobulin (IVIG) therapy were independent risk factors of initial coronary severity but were not associated with the late coronary outcomes, even in severity stratified subgroups. Conclusions The coronary severity 1 month after KD onset is most crucial to the late coronary outcomes. Although IVIG use improves the initial severity of coronary lesions, it does not further modify the long-term fate of coronary aneurysms.

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.

Association of the C677T methylenetetrahydrofolate reductase mutation with congenital heart diseases

Background.  To investigate whether the cytosine‐to‐thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (MTHFR) is associated with congenital heart diseases (CHD), using high throughput heteroduplex analysis based upon the powerful technique of denaturing high‐performance liquid chromatography.

Comparison of 3 risk estimation methods for predicting cardiac outcomes in pregnant women with congenital heart disease

BACKGROUND Three risk estimation methods for predicting the cardiac outcomes of pregnancy in women with heart disease have been proposed. This study was designed to compare their prediction performance in an Asian cohort with congenital heart disease (CHD). METHODS AND RESULTS This study enrolled pregnant women with CHD who delivered their babies after the 20th gestational week between 1985 and 2011. Of 268 pregnancies in 190 women with CHD, 18 (6.7%) had cardiac complications. The incidence of maternal cardiac events among women with a CARPREG index of 0, 1 or 2 was 3.4%, 27.3% and 100%. The incidence was 2.7%, 8.6%, 11.1%, 40% and 17.6% for those with a ZAHARA score 0-0.5, 0.51-1.5, 1.51-2.5, 2.51-3.5 and >3.5. Among patients with a modified World Health Organization (WHO) classification I, II, III and IV, the incidence of maternal cardiac events was 0%, 4.0%, 12.2% and 25.7%. The c-statistic was 0.732 (95% confidence interval (CI): 0.589, 0.876; P<0.001) for the CARPREG score, 0.737 (95% CI: 0.611, 0.864; P=0.001) for the ZAHARA score and 0.827 (95% CI: 0.745, 0.909; P<0.001) for the WHO classification. CONCLUSIONS All 3 risk estimation methods had good performance in predicting maternal cardiac outcomes; however, the modified WHO classification demonstrated superior discrimination and calibration.