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Biomedical subjects

Arthur J Moss

Publications and source records attributed to Arthur J Moss.

At least 109 records · Page 6Linked to original sources
PubMed2003

Implantable cardioverter defibrillator in high-risk long QT syndrome patients.

INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are increasingly being used in high-risk long QT syndrome (LQTS) patients, but there are limited data regarding clinical experience with this therapeutic modality. The aim of this study is to describe the clinical characteristics of 125 LQTS patients treated with ICDs compared with LQTS patients having similar risk indications who were not treated with ICDs. Among 125 LQTS patients with ICDs, there were 54 cardiac arrest survivors, 19 patients who had ICDs implanted due to recurrent syncope despite beta-blocker therapy, and 52 patients with ICDs implanted due to other reasons, including syncope and LQTS-related sudden death in a close family member. Patients with cardiac arrest and those with recurrent syncope despite beta-blocker therapy (n = 73) were compared to 161 LQTS patients who had similar indications (89 cardiac arrest and 72 recurrent syncope despite beta-blocker therapy) but did not receive ICDs. Total mortality was the endpoint of the analysis. There was 1 (1.3%) death in 73 ICD patients followed an average of 3 years, whereas there were 26 deaths (16%) in non-ICD patients during mean 8-year follow-up (P = 0.07 from log rank test from Kaplan-Meier curves). CONCLUSION: ICDs provide an important therapeutic option to prevent sudden arrhythmic death in high-risk LQTS patients. A long-term prospective study is needed to determine the benefit of this therapeutic modality in LQTS patients.

Adolescent↗
PubMed2003

Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome.

INTRODUCTION: Recent data showed that long QT syndrome (LQTS) patients with mutations in the pore region of the HERG (LQT2) gene have significantly higher risk of cardiac events than subjects with mutations in the non-pore region. The aim of this study was to determine whether there is an association between the location of mutations in the KCNQ1 gene and cardiac events in LQT1 patients. METHODS AND RESULTS: The study population consisted of 294 LQT1 patients with KCNQ1 gene mutations. Demographic, clinical, and follow-up information was compared among subjects with different locations of KCNQ1 mutations defined as pre-pore region including N-terminus (1-278), pore region (279-354), and post-pore region including C-terminus (>354). Cardiac events observed during follow-up from birth until age of last contact or age 40 years were defined as syncope, cardiac arrest, or sudden death. There were 164 (56%) LQT1 patients with pre-pore mutations, 101 (34%) with pore mutations, and 29 (10%) with post-pore mutations. QTc duration did not differ significantly among the three subgroups (mean QTc = 494, 487, and 501 ms, respectively). There was no significant difference between groups with regard to the risk of cardiac events by age 40 years. CONCLUSION: There are no significant differences in clinical presentation, ECG parameters, and cardiac events among LQT1 patients with different locations of KCNQ1 mutations. These findings indicate that factors other than location of mutation influence clinical phenotype in patients with LQT1 mutations.

Adult↗
PubMed2003

Novel compound heterozygous mutations in the KCNQ1 gene associated with autosomal recessive long QT syndrome (Jervell and Lange-Nielsen syndrome).

BACKGROUND: The Jervell and Lange-Nielsen syndrome (JLNS) is the autosomal recessive form of long QT syndrome (LQTS)--a familial cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. JLNS is associated with sensorineural deafness and has been shown to occur with homozygous mutations in KCNQ1 or KCNE1 in JLNS families in which QTc prolongation is inherited as a dominant trait. This study investigated the molecular pathology of a family with clinical evidence of JLNS. METHODS AND RESULTS: Single-strand conformation polymorphism, denaturing high performance liquid chromatography, and DNA sequencing analyses were used to screen for KCNQ1 mutations. Novel compound heterozygous nonsense mutations R518X/Q530X in the C-terminus of KCNQ1 were identified in both affected dizygotic twins; both the parents and a sibling each carried only one of the mutant alleles and were asymptomatic with modestly prolonged QTc intervals (0.46, 0.50, and 0.45 seconds, respectively). These two nonsense mutations lead to premature termination of C-terminus with truncation of the postulated assembly domain. CONCLUSION: Novel compound heterozygous nonsense mutations in C-terminus of KCNQ1 can cause JLNS.

Chromatography, High Pressure Liquid↗
PubMed2003

Long QT syndrome: novel insights into the mechanisms of cardiac arrhythmias.

The congenital long QT syndrome is a rare disorder in which mutation carriers are at risk for polymorphic ventricular tachycardia and/or sudden cardiac death. Discovery and analysis of gene mutations associated with variants of this disorder have provided novel insight into mechanisms of cardiac arrhythmia and have raised the possibility of mutation-specific therapeutic intervention.

Animals↗
PubMed2002

Usefulness of standard electrocardiographic parameters for predicting cardiac events after acute myocardial infarction during modern treatment era.

Comprehensive information about the independent value of different electrocardiographic (ECG) variables in predicting cardiac events after acute myocardial infarction (AMI) in the era of modern therapy is limited. Patients (n = 1,034) underwent standard electrocardiography from 5 to 7 days after an AMI. Several time intervals and PQRST abnormalities were analyzed from the electrocardiogram. During a mean +/- SD follow-up of 752 +/- 301 days on average, 42 patients (4%) experienced cardiac death, and 259 patients (25%) a cardiac death, nonfatal AMI, or unstable angina. Several ECG variables had a significant association with cardiac events in univariate comparisons. After adjustment for all risk variables in the Cox hazards model, lateral ST-segment depression (hazard ratio [HR] 4.76, 95% confidence interval [CI] 2.40 to 9.44, p <0.0001) and atrial abnormality with a terminal deflection of the P wave > or =0.1 mV deep and > or =40 ms in duration in lead V(1) (HR 2.46, 95% CI 1.25 to 4.82, p = 0.009) were the only ECG variables that independently predicted cardiac death. Lateral ST-segment depression also predicted the combined end point of cardiac death/nonfatal AMI/unstable angina in this model (HR 1.49, 95% CI 1.14 to 1.94, p = 0.003). In conclusion, lateral ST depression and atrial abnormality on the electrocardiogram are independent predictors of cardiac death after AMI. Lateral ST depression is also associated with ischemic cardiac events.

Electrocardiography↗
PubMed2002

Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.

BACKGROUND: Patients with reduced left ventricular function after myocardial infarction are at risk for life-threatening ventricular arrhythmias. This randomized trial was designed to evaluate the effect of an implantable defibrillator on survival in such patients. METHODS: Over the course of four years, we enrolled 1232 patients with a prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less. Patients were randomly assigned in a 3:2 ratio to receive an implantable defibrillator (742 patients) or conventional medical therapy (490 patients). Invasive electrophysiological testing for risk stratification was not required. Death from any cause was the end point. RESULTS: The clinical characteristics at base line and the prevalence of medication use at the time of the last follow-up visit were similar in the two treatment groups. During an average follow-up of 20 months, the mortality rates were 19.8 percent in the conventional-therapy group and 14.2 percent in the defibrillator group. The hazard ratio for the risk of death from any cause in the defibrillator group as compared with the conventional-therapy group was 0.69 (95 percent confidence interval, 0.51 to 0.93; P=0.016). The effect of defibrillator therapy on survival was similar in subgroup analyses stratified according to age, sex, ejection fraction, New York Heart Association class, and the QRS interval. CONCLUSIONS: In patients with a prior myocardial infarction and advanced left ventricular dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy.

Adrenergic beta-Antagonists↗
PubMed2002

Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel.

BACKGROUND: The hereditary long-QT syndrome is characterized by prolonged ventricular repolarization and a variable clinical course with arrhythmia-related syncope and sudden death. Mutations involving the human ether-a-go-go-related gene (HERG) channel are responsible for the LQT2 form of long-QT syndrome, and in cellular expression studies these mutations are associated with reduction in the rapid component of the delayed rectifier repolarizing current (I(Kr)). We investigated the clinical features and prognostic implications of mutations involving pore and nonpore regions of the HERG channel in the LQT2 form of this disorder. METHODS AND RESULTS: A total of 44 different HERG mutations were identified in 201 subjects, with 14 mutations located in the pore region (amino acid residues 550 through 650). Thirty-five subjects had mutations in the pore region and 166 in nonpore regions. Follow-up extended through age 40 years. Subjects with pore mutations had more severe clinical manifestations of the genetic disorder and experienced a higher frequency (74% versus 35%; P<0.001) of arrhythmia-related cardiac events occurring at earlier age than did subjects with nonpore mutations. Multivariate Cox proportional hazard regression analysis revealed that pore mutations dominated the risk, with hazard ratios in the range of 11 (P<0.0001) for QTc at 500 ms, with a 16% increase in the pore hazard ratio for each 10-ms increase in QTc. CONCLUSION: Patients with mutations in the pore region of the HERG gene are at markedly increased risk for arrhythmia-related cardiac events compared with patients with nonpore mutations.

Adolescent↗
PubMed2002

Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome.

Jervell and Lange-Nielsen syndrome (JLNS) is characterized by sensorineural deafness, QT prolongation, abnormal T waves, ventricular tachyarrhythmias, and autosomal recessive inheritance. Previously homozygous mutations in the potassium channel-encoding genes, KvLQT1 (alpha-subunit) and KCNE1 (beta-subunit), have been described in consanguineous families with JLNS. We screened two nonconsanguineous families with JLNS for mutations in KvLQT1, using single-strand conformation polymorphism analysis, denaturing high-performance liquid chromatography, and DNA sequencing. In one family, a missense mutation was identified in exon 6 of KvLQT1 on the maternal side, resulting in a glycine to aspartic acid substitution at codon 269 (G269D). The apparently normal father had an incompletely penetrant missense mutation in exon 3 of KvLQT1, introducing a premature stop codon at position 171. In the other family, a missense mutation resulting in the substitution of asparagine for aspartic acid at codon 202 (D202N) was identified in the mother and maternal grandmother, who had QTc prolongation (borderline in the mother), while the father and paternal grandfather, who were clinically normal, had a deletion of nucleotide 585, resulting in a frameshift and premature termination. In both families, the proband inherited both mutations. In this report we provide evidence that not only homozygous but also compound heterozygous mutations in KvLQT1 may cause JLNS in nonconsanguineous families. Incomplete penetrance in individuals with mutations appears to be frequent, indicating a higher prevalence of mutations than estimated previously. Interestingly, mutations resulting in truncation of the protein appear to be benign, with heterozygous carriers being asymptomatic.

Base Sequence↗
PubMed2002

T-wave patterns associated with the hereditary long QT syndrome.

Mutations involving 6 different ion-channel genes have been identified in subjects with the hereditary Long QT Syndrome. These gene mutations result in structural and functional changes in ion-channel proteins with resultant alterations in potassium and sodium repolarization currents that affect the morphologic features of electrocardiographic repolarization. This review highlights the genotype-phenotype associations related to ventricular repolarization that have been reported in the LQTS literature, with particular focus on ECG T-wave patterns in LQT1, LQT2, and LQT3 genotypes.

Adolescent↗