Cardiovascular Diseases ; diagnosis ; therapy ; Child ; Heart Defects, Congenital ; diagnosis ; therapy ; Humans

Acetylation ; Animals ; Child ; DNA Methylation ; Epigenesis, Genetic ; Heart ; physiology ; Heart Defects, Congenital ; etiology ; genetics ; metabolism ; Histone Acetyltransferases ; metabolism ; Histone Deacetylases ; metabolism ; Histones ; chemistry ; genetics ; physiology ; Humans ; Protein Processing, Post-Translational ; Transcription Factors ; metabolism

OBJECTIVETo evaluate the efficacy and safety of evaluation,treatment and follow-up of Kawasaki coronary artery disease based on the clinical severity classification.

METHODThis study evaluated 52 patients admitted to the Children's Hospital of Fudan University between July 2005 and December 2013 who were diagnosed with Kawasaki Disease with coronary artery disease.Inclusion criteria were a disease course of more than two months, initial echocardiography showing severity of grade IV and above, and confirmation of disease severity by angiography. Of those studies, 44 were male and eight were female, aged 6 to 142 (average 41) months. Treatment was planned according to protocols in "Suggestions for Management of Kawasaki Coronary Artery Disease" with follow-up. Those patients with grade IV and above confirmed by angiogram were given oral low-dose asprin and warfarin, and those with grade Vb were given coronary artery bypass grafting (CABG) after comprehensive evaluation. Analysis was carried out for diagnosis, treatment, complications, and results of follow-up.

RESULT(1) Satisfied images were shown by the angiography of all 52 cases. Forty five patients (86%) had giant aneurysm or multiple aneurysms, with thrombosis found in 10 of 45 patients (22%). Coronary artery lesions occurred in 138 coronary branches, and more common in left anterior descending branch (47 branches, with incidence 34%) and right coronary artery (48 branches, with incidence 35%). There were no complications during or after angiography. (2) After angiography, 49 patients remained at grade IV or above, and three improved to grade III. Ultimately, clinical severities of coronary artery disease included three patients at grade III, 31 patients at grade IV, nine patients at grade Va, and nine patients at grade Vb. (3) Thirty-eight patients were properly using aspirin and warfarin, and two patients with severely elevated international normalized ratio (INR) levels presented with knee joint and gastric hemorrhage, both of which were treated successfully.Patients with INR levels between 1.5 and 2.5 did not show signs of hemorrhage. (4) In follow-up visits between 6 months and 8 years, one patient had representation of thrombosis on angiography, but did not lead to coronary stenosis; four patients were improved from grade IV to either grade III or II. The remaining showed no new thrombotic formation or stenosis. (5) Of the nine grade Vb patients, five underwent coronary artery bypass grafting. The youngest of these patients, a 22 months old girl, died intraoperatively. The remaining four recovered postoperatively and were followed up for 8 to 90 months. One patient had a preoperative left ventricular ejection fraction (LVEF) of only 32.8%, with LVEF remaining abnormal post-CABG, between 35% and 44%. The remaining three patients had normal heart size, cardiac function, and electrocardiogram.Of the other four grade Vb patients, two were contraindicated for surgery due to severe heart failure and loss of myocardial activity. Two other cases are being followed up closely due to their young age of 9 months.

CONCLUSIONCoronary angiography is safe and efficacious in children, and even in infants.It is the current gold standard tool for grading Kawasaki coronary artery disease. Proper anticoagulation therapy can markedly decrease the incidence of coronary artery occlusion in patients with Kawasaki coronary artery disease. Safe ranges of corrected INR should be between 1.5 and 2.5 after taking warfarin. CABG is an effective treatment for severe coronary artery disease with myocardial ischemia.

Aspirin ; therapeutic use ; Child ; Child, Preschool ; Coronary Angiography ; Coronary Artery Bypass ; Coronary Artery Disease ; complications ; therapy ; Disease Management ; Echocardiography ; Electrocardiography ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; therapy ; Treatment Outcome ; Ventricular Function, Left ; Warfarin ; therapeutic use

OBJECTIVETo screen for genomic copy number variations (CNVs) in two unrelated neonates with multiple congenital abnormalities using Affymetrix SNP chip and try to find the critical region associated with congenital heart disease.

METHODTwo neonates were tested for genomic copy number variations by using Cytogenetic SNP chip.Rare CNVs with potential clinical significance were selected of which deletion segments' size was larger than 50 kb and duplication segments' size was larger than 150 kb based on the analysis of ChAs software, without false positive CNVs and segments of normal population. The identified CNVs were compared with those of the cases in DECIPHER and ISCA databases.

RESULTEleven rare CNVs with size from 546.6-27 892 kb were identified in the 2 neonates. The deletion region and size of case 1 were 8p23.3-p23.1 (387 912-11 506 771 bp) and 11.1 Mb respectively, the duplication region and size of case 1 were 8p23.1-p11.1 (11 508 387-43 321 279 bp) and 31.8 Mb respectively. The deletion region and size of case 2 were 8p23.3-p23.1 (46 385-7 809 878 bp) and 7.8 Mb respectively, the duplication region and size of case 2 were 8p23.1-p11.21 (12 260 914-40 917 092 bp) and 28.7 Mb respectively. The comparison with Decipher and ISCA databases supported previous viewpoint that 8p23.1 had been associated with congenital heart disease and the region between 7 809 878-11 506 771 bp may play a role in the severe cardiac defects associated with 8p23.1 deletions. Case 1 had serious cardiac abnormalities whose GATA4 was located in the duplication segment and the copy number increased while SOX7 was located in the deletion segment and the copy number decreased.

CONCLUSIONThe region between 7 809 878-11 506 771 bp in 8p23.1 is associated with heart defects and copy number variants of SOX7 and GATA4 may result in congenital heart disease.

Abnormalities, Multiple ; diagnostic imaging ; genetics ; Chromosome Deletion ; Chromosome Duplication ; genetics ; Chromosome Inversion ; Chromosomes, Human, Pair 8 ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Female ; Heart Defects, Congenital ; diagnostic imaging ; genetics ; Humans ; Infant, Newborn ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Ultrasonography