ABSTRACT
OBJECTIVES: Genetic testing, a gold standard for long QT syndrome (LQTS) diagnosis, is time-consuming and costly when all the 15 candidate genes are screened. Since genotype-specific ECG patterns are present in most LQT1-3 mutation carriers, we tested the utility of ECG-guided genotyping in a large cohort of Chinese LQTS patients. METHODS AND RESULTS: We enrolled 230 patients (26 ± 17 years, 66% female) with a clinical diagnosis of LQTS. Genotypes were predicted as LQT1-3 based on the presence of ECG patterns typical for each genotype in 200 patients (85 LQT1, 110 LQT2 and 5 LQT3). Family-based genotype prediction was also conducted if gene-specific ECG patterns were found in other affected family members. Mutational screening identified 104 mutations (44% novel), i.e. 46 KCNQ1, 54 KCNH2 and 4 SCN5A mutations. The overall predictive accuracy of ECG-guided genotyping was 79% (157/200) and 79% (67/85), 78% (86/110) and 80% (4/5) for LQT1, LQT2 and LQT3, respectively. The predictive accuracy was 98% (42/43) when family-based ECG assessment was performed. CONCLUSIONS: From this large-scale genotyping study, we found that LQT2 is the most common genotype among the Chinese. Family-based ECG-guided genotyping is highly accurate. ECG-guided genotyping is time- and cost-effective. We therefore recommend it as an optimal approach for the genetic diagnosis of LQTS.
Subject(s)
Genotype , KCNQ1 Potassium Channel/genetics , Long QT Syndrome/genetics , Adolescent , Adult , Asian People/genetics , China , Cohort Studies , Electrocardiography , Female , Gene Frequency , Genetic Testing/methods , Humans , Long QT Syndrome/diagnosis , Male , Middle Aged , Mutation , Phenotype , Polymerase Chain Reaction , Registries , Young AdultABSTRACT
OBJECTIVE: The purpose of this study was to screen genetic variations in plakophilin-2 (PKP2) gene in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and investigate the differences in clinical features between mutation and no-mutation groups. METHODS: Thirty unrelated Chinese patients clinically diagnosed with ARVC/D and 50 healthy controls were included. Genomic DNA was isolated from peripheral blood samples. PCR and direct sequencing were used to detect variations in PKP2 gene. RESULTS: Eight PKP2 mutant variants were identified in 10 ARVC/D patients (8 men, 2 women). Among the eight mutation, three (c.2194C>T, c. 1170+ 1G>A and c. 810_813delGGTC) were novel mutation. Clinical features of the PKP2 mutation group were similar to those of the non-mutation group. CONCLUSIONS: The rate of PKP2 mutation is 33.3% (10/30) in ARVC/D patients. The penetrance of PKP2 mutation for ARVC/D tends to be higher in man patients. No significant differences could be detected in phenotype characteristics between patients with and without PKP2 mutation.
Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/genetics , Asian People/genetics , Plakophilins/genetics , Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Mutation , PhenotypeABSTRACT
BACKGROUND: Use of intensive anticoagulation and antiplatelet therapy in acute myocardial infarction (AMI) potentially increases the risk of bleeding complications during percutaneous coronary intervention via the transfemoral route. Recently, the transradial access has been intensively employed as an alternative means for diagnostic and interventional procedures. A low incidence of vascular access site bleeding complications suggests that the transradial access is a safe alternative to the transfemoral technique in patients with AMI. The safety and efficacy of transradial access for emergent percutaneous coronary intervention in patients with AMI has not been investigated in the People's Republic of China. METHODS: We analyzed data from our single-center registry on 596 consecutive patients between October 2003 and October 2010. The patients were retrospectively divided into a transradial group (n = 296) and a transfemoral group (n = 300). A dedicated doctor was appointed to collect the following data: puncture time, coronary angiography time, percutaneous coronary intervention time, X-ray exposure time, duration of hospitalization, and complication rates associated with puncture, such as puncture site bleeding, hematoma, pseudoaneurysm, and major adverse cardiac events. RESULTS: There were no significant differences in baseline characteristics and angiographic findings between the two groups. There were also no significant differences in coronary angiography time (8.2 ± 2.4 versus 7.6 ± 2.0 minutes), percutaneous coronary intervention time (30 ± 6.8 versus 29.6 ± 8.1 minutes), or X-ray exposure time (4.6 ± 1.4 versus 4.4 ± 1.3 minutes) between the groups. There were significant differences in puncture time (4.4 ± 1.6 versus 2.4 ± 0.8 minutes) and duration of hospitalization (3.2 ± 1.6 versus 5.4 ± 1.8 days) between the groups (P < 0.001). The complication rate using transradial access was 2.03% (6/296) versus 6.0% (18/300) using transfemoral access (P < 0.0001). CONCLUSION: Transradial access for emergent percutaneous coronary intervention is safe and effective in patients with AMI, and it is suggested that this route could be used more widely in these patients.
Subject(s)
Femoral Artery , Myocardial Infarction/surgery , Outcome Assessment, Health Care , Percutaneous Coronary Intervention/methods , Radial Artery , Acute Disease , Aged , China , Coronary Angiography , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Patient Safety , Percutaneous Coronary Intervention/adverse effects , Registries , Retrospective StudiesABSTRACT
Coronary artery anomalies (CAAs) are present at birth, but are usually asymptomatic and are found during coronary angiography or multi-slice computed tomography (MSCT) detection. The most common coronary anomaly is the separating origin of left anterior descending coronary artery (LAD) and left circumflex artery (LCX) from the left sinus of Valsalva, and this variant is benign. Herein, we present three extremely rare cases of anomalous right coronary artery (RCA) detected incidentally during routine coronary angiography and confirmed by multi-slice computed tomography (MSCT) technique. All the anomalous right coronary artery coursed between the pulmonary artery and aorta. We discuss how to make an accurate diagnosis for appropriate management.
Subject(s)
Coronary Vessel Anomalies/diagnostic imaging , Aged , Aorta , Coronary Angiography , Female , Humans , Incidental Findings , Male , Middle Aged , Pulmonary Artery/diagnostic imaging , Sinus of Valsalva/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
This case report we presented is that the anomalous left main coronary artery (LMCA) originates from the proximal segment of right coronary artery. In order to confirm the origin and course of the anomalous LMCA, a multi-slice computed tomography (MSCT) of the heart was performed on a 64-slice machine (Philips 64 Slice, Philips, USA) after 6 months of coronary angiography operation. The results showed that the anomalous LMCA originates from the proximal segment of right coronary artery, lies posteriorly to the aorta before taking acute sharply to go between the aorta and left atrium. It was classified as R-II P subtype according to Lipton's classification. It is a rare case in the clinical practice.
Subject(s)
Coronary Vessel Anomalies/diagnosis , Coronary Vessels/pathology , Aged , Humans , MaleABSTRACT
OBJECTIVE: Hereditary long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of QT interval on electrocardiograms (ECGs) and syncope and sudden death caused by a specific multi-polymorphic ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in cardiac sodium channel gene SCN5A; potassium channel subunit genes KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2; calcium channel gene Cav2.1. and ankyrin-B gene ANK2. METHODS: We characterized 77 Chinese LQTS patients with clinical manifestations and mutations in the main LQTS genes, KCNQ1 and KCNH2 using PCR and sequence analysis. RESULTS: The spectrum of ST-T-wave patterns of 24 (31.2%) probands were considered as LQT1, 42 (54.5%) as LQT2 and 3 (3.9%) as LQT3. The remaining 8 (10.3%) could not be characterized. The average age for this population of LQTS patients was (27.6 +/- 16.4) years and the average QTc (561 +/- 70) ms, and the age of the first syncopal attack was (17.6 +/- 14.7) years. The triggering factors for cardiac events happening in these mutation carriers included physical exercise, emotional excitement and auditory irritation. We identified 4 KCNQ1 mutations and 7 KCNH2 mutations. Six of them were first identified with some data already shown. In this paper we showed the data of 6 other mutations. CONCLUSIONS: LQT2 is the most common type of LQTS in Chinese; 2 mutations of KCNQ1 and KCNH2 were first identified in this report; there are some differences between Chinese and North American or European LQTS patients in clinical characters and ECG.
Subject(s)
Ether-A-Go-Go Potassium Channels/genetics , KCNQ1 Potassium Channel/genetics , Long QT Syndrome/genetics , Mutation , Adolescent , Adult , Child , China , ERG1 Potassium Channel , Electrocardiography , Female , Humans , Male , Pedigree , Polymorphism, Single-Stranded ConformationalABSTRACT
OBJECTIVE: Jervell and Lange-Nielsen syndrome (JLNS) is a severe cardioauditory syndrome manifested as QT interval prolongation, abnormal T waves, and relative bradycardia ventricular tachyarrhythmias. In this report, we screened a nonconsanguineous families with JLNS for mutations in KCNQ1. METHODS: Mutation analysis was performed by using purified PCR products to direct sequence analysis on an ABI-3730XL automated DNA sequencer. The whole sequence of proband' KCNQ1 was screened firstly, then screened the mutation exon sequences of others of the family and 50 unrelated normal persons. RESULTS: A heterogeneous mutation was identified in the patients of the JLNS family, a missense mutation (G-->T) at nucleotide 917 encoded in exon 6 of KCNQ1. This substitution leads to a change from glycine to Valine at codon 306(G306V) corresponding to the S5 transmembrane segment of KCNQ1. The other normal members of the family and 50 unrelated normal persons were not identified this mutation. CONCLUSION: The result suggested that not only homozygous mutations or compound heterozygous mutations in KCNQ1 could cause Jervell-Lange-Nielsen syndrome, the single heterozygous mutation may also cause Jervell-Lange-Nielsen syndrome.
Subject(s)
Jervell-Lange Nielsen Syndrome/genetics , KCNQ1 Potassium Channel/genetics , Mutation, Missense , Adolescent , Adult , Aged , Child , Female , Genotype , Humans , Long QT Syndrome/genetics , Male , Middle Aged , Pedigree , Young AdultABSTRACT
OBJECTIVE: To search for the mutations of potassium voltage-gated channel, KQT-like subfamily member 1(KCNQ1) gene in 31 Chinese long QT syndrome(LQTS) families. METHODS: Due to the genetic heterogeneity, the genotype of patients was first predicted based on the spectrum of ST-T-wave patterns on ECG. Ten of 31 probands were considered as LQT1. Then the mutation of KCNQ1 gene was screened by the polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) technique combined with DNA sequencing in all members of these 10 families. To avoid omitting some LQT1 patients without typical characteristics and also to do methodological comparison, the mutations of KCNQ1 gene on 16 exons were screened by PCR and direct DNA sequencing in the rest 21 non-LQT1 probands only. Co-segregation analysis was carried out after the finding of an abnormal sequence. In case that the abnormality existed in patients only, the test of such exon was performed in 50 irrelevant normal individuals. RESULTS: Two missense mutations and three single nucleotide polymorphisms (SNPs) were found in the LQT1 predicted families. The two mutations were S277L (1 family) and G306V (1 family) in exon 5 and were not reported previously. Three polymorphisms were 435C-->T (7 families), 1632C-->A (1 family), and IVS1+9 C-->G (3 families). Only a splice mutation IVS1+5G-->A (2 families) and a polymorphism IVS10+18C-->T (1 family) were found in the non-LQT1 predicted probands. All three mutations were localized within the functional domain of KCNQ1 and were co-segregated with the disease, and were not found in 50 normal individuals. CONCLUSION: Two novel missense mutations, 1 splice mutation and four SNPs on KCNQ1 gene were found in the 31 LQTS families. Combined with ECG-based genotype prediction, PCR-SSCP could find most mutations on KCNQ1 and be a simple and economic method for screening LQTS.
Subject(s)
Long QT Syndrome/genetics , Mutation , Potassium Channels, Voltage-Gated , Potassium Channels/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , KCNQ Potassium Channels , KCNQ1 Potassium Channel , Male , Middle AgedABSTRACT
OBJECTIVE: To evaluate the spectrum of ST-T-wave patterns in Chinese patients with hereditary long-QT syndrome. METHODS: ECGs of 61 families were studied to determine ST-T-wave patterns. Genotypes were identified by sequencing. RESULTS: 32 cases showed similarity to LQT1, 41 to LQT2 and 2 to LQT3 in ECG, and 3 cases could not be classified. QTc of the patients with symptom was (0.547 +/- 0.08) sec and that of the patients without symptoms was (0.526 +/- 0.06) sec, both were much longer than that of normal members of the families. T wave patterns were different in 48 cases at different time. QTc difference in a same person between two times or DeltaQTc were as follows: (0.048 +/- 0.057) sec in patients and (0.023 +/- 0.017) sec in normal members (P < 0.001). 12 cases of LQT1 and 11 cases of LQT2 were identified by genotype sequencing. CONCLUSIONS: There are some differences in ST-T waves between these Chinese hereditary long-QT syndrome patients and European and American patterns. These patients showed greater variability in ST-T wave pattern including the changes in the same type, in the same pedigree and in the same patients at different time.
Subject(s)
Electrocardiography, Ambulatory , Long QT Syndrome/genetics , Adolescent , Adult , Female , Genetic Linkage , Genotype , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Male , Middle AgedABSTRACT
To assess the clinical features and the management of congenital long QT syndrome (LQTS) in China, we collected the clinical data of 54 LQTS patients (14 males and 40 females) from our newly established national registry. All patients were symptomatic, with syncope being the most common symptom. The average age when the first symptoms occurred was 17.9 +/- 15.6 (range, 0.5-62) years; 55.6% of them had the first symptoms before the age of 20. The most common triggers of the symptoms were physical exercise or emotional stress. The average corrected QT interval was 0.55 +/- 0.08 s. Using ECG criteria, there were 14 (25.9%) LQT1 patients, 28 (51.9%) LQT2, and 2 (3.7%) LQT3. Thirty (55.6%) patients were treated with Beta-blockers at the time of enrollment, with propranolol being the most commonly used drug, with an average daily dose of 57.5 +/- 39.1 mg. Four patients underwent left cardiac sympathectomy. After an average follow-up of 24.9 +/- 13.2 months, 3.1% (1/32) of patients with antiadrenergic therapy and 9.1% (2/22) without antiadrengergic therapy died of sudden cardiac death ( P < 0.05). We concluded that LQT2 might be the most common subtype in these patients. Antiadrenergic treatment was underused, raising the urgent need for educating both physicians and patients on the nature of the disease and its optimal antiadrenergic therapy.
Subject(s)
Long QT Syndrome/congenital , Registries/statistics & numerical data , Adrenergic beta-Antagonists/therapeutic use , Adult , China/epidemiology , Electrocardiography , Female , Humans , Long QT Syndrome/epidemiology , Long QT Syndrome/therapy , Male , Propranolol/therapeutic use , SympathectomyABSTRACT
OBJECTIVE: To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese. METHODS: Thirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing. RESULTS: Two novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 + 18C > T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients. CONCLUSIONS: The mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.
Subject(s)
Cation Transport Proteins , DNA-Binding Proteins , Long QT Syndrome/genetics , Mutation , Potassium Channels, Voltage-Gated , Potassium Channels/genetics , Trans-Activators , Asian People , China , ERG1 Potassium Channel , Ether-A-Go-Go Potassium Channels , Female , Humans , KCNQ Potassium Channels , KCNQ1 Potassium Channel , Male , Transcriptional Regulator ERGABSTRACT
The long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of the QT interval on electrocardiograms (ECGs), syncope and sudden death caused by a specific ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in ion channel genes including the cardiac sodium channel gene SCN5A, and potassium channel subunit genes KCNQ1, KCNH2, KCNE1, and KCNE2. Little information is available about LQTS mutations in the Chinese population. In this study, we characterized 42 Chinese LQTS families for mutations in the two most common LQTS genes, KCNQ1 and KCNH2. We report here the identification of four novel KCNQ1 mutations and three novel KCNH2 mutations. The KCNQ1 mutations include L191P in the S2-S3 cytoplasmic loop, F275S and S277L in the S5 transmembrane domain, and G306V in the channel pore. The KCNH2 mutations include L413P in transmembrane domain S1, E444D in the extracellular loop between S1 and S2, and L559H in domain S5. The location and character of these mutations expand the spectrum of KCNQ1 and KCNH2 mutations causing LQTS. Excitement, exercises, and stress appear to be the triggers for developing cardiac events (syncope, sudden death) for LQTS patients with KCNQ1 mutations F275S, S277L, and G306V, and all three KCNH2 mutations L413P, E444D and L559H. In contrast, cardiac events for an LQTS patient with KCNQ1 mutation L191P occurred during sleep or awakening from sleep. KCNH2 mutations L413P and L559H are associated with the bifid T waves on ECGs. Inderal or propanolol (a beta blocker) appears to be effective in preventing arrhythmias and syncope for an LQTS patient with the KCNQ1 L191P mutation.