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Biomedical subjects

A J Moss

Publications and source records attributed to A J Moss.

At least 91 records · Page 5Linked to original sources
PubMed1996

What can be expected for the management of heart failure in the near future?

Further reduction in the morbidity and mortality from diseases associated with heart failure is to be expected by the early introduction of strategies aimed at preventing cardiac damage. In the future, ACE inhibitors, beta-adrenergic blocking agents and type III antiarrhythmic agents, as well as pacemakers, will be used judiciously and in combination following better risk profiling using non-invasive techniques. Cardiac transplantation could be a more widely used treatment for end-stage cardiac disease. Ongoing randomized studies are revealing the usefulness of various pharmaceutical products as well as implanted defibrillators. In the more distant future, anti-endothelin therapy, cardiac autoantibody immunotherapy, cardiac-specific inhibition of angiotensin-converting enzyme and/or normalization of autonomic parasympathetic activity by parasympathomimetic agents may prove to be additional tools for reducing the complications from cardiac disease.

Adrenergic beta-Antagonists↗
PubMed1995

ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome.

BACKGROUND: The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. METHODS AND RESULTS: Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QTonset-c, QTpeak-c, QTc, and Tduration-c, in milliseconds) and the absolute height of the T wave (Tamplitude, in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n = 47), 7 (n = 30), and 11 (n = 76). Genotypic data were used to define each family member as being affected or unaffected with long QT syndrome. Affected members of all six families had longer QT intervals (QTonset-c, QTpeak-c, or QTc) than unaffected family members (P < .01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QTonset-c was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QTonset-c [mean +/- SD]: chromosome 3, 341 +/- 42 ms; chromosome 7, 290 +/- 56 ms; chromosome 11, 243 +/- 73 ms; P < .001); Tamplitude was generally quite small in the chromosome 7 genotype (lead II Tamplitude, mV: chromosome 3, 0.36 +/- 0.14; chromosome 7, 0.13 +/- 0.07; chromosome 11, 0.37 +/- 0.17; P < .001); and Tduration was particularly long in the chromosome 11 genotype (lead II Tduration-c: chromosome 3, 187 +/- 33 ms; chromosome 7, 191 +/- 51 ms; chromosome 11, 262 +/- 65 ms; P < .001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes. CONCLUSIONS: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.

Adult↗
PubMed1995

SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome.

Long QT syndrome (LQT) is an inherited disorder that causes sudden death from cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. We previously mapped three LQT loci: LQT1 on chromosome 11p15.5, LQT2 on 7q35-36, and LQT3 on 3p21-24. Here we report genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene. Single strand conformation polymorphism and DNA sequence analyses reveal identical intragenic deletions of SCN5A in affected members of two unrelated LQT families. The deleted sequences reside in a region that is important for channel inactivation. These data suggest that mutations in SCN5A cause chromosome 3-linked LQT and indicate a likely cellular mechanism for this disorder.

Amino Acid Sequence↗
PubMed1995

Risk of cardiac events in family members of patients with long QT syndrome.

OBJECTIVES: This study sought to identify risk factors for cardiac events (syncope, aborted cardiac arrest or sudden cardiac death) in family members of patients with the long QT syndrome. BACKGROUND: Patients with the long QT syndrome are known to be at high risk for cardiac events. Whenever the first member of a family is identified as having the long QT syndrome (proband), there is concern regarding the likelihood of cardiac events in other family members. METHODS: A multivariate logistic regression model was used to evaluate the risk of cardiac events in 637 family members who were first- and second-degree relatives of 151 probands with the long QT syndrome and in a subset of 513 family members who were not receiving beta-adrenergic blocking agents. There were 293 first-degree (46%) and 344 second-degree relatives (54%) (293 men [46%], 344 women [54%]). Fifteen percent of the family members had a corrected QT interval (QTc) > 0.44 s, and relative tachycardia and bradycardia were observed in 12% and 25%, respectively. RESULTS: The risk of cardiac events occurring before age 40 in family members not taking beta-blockers was influenced by the QTc interval (odds ratio [OR] 1.18/0.01 increase in QTc value; 95% confidence interval [CI] 1.12 to 1.24), relative tachycardia (OR 2.21, 95% CI 0.97 to 5.02) or bradycardia (OR 2.24, 95% CI 1.10 to 4.56) and an interaction term combining gender and closeness of the relationship to the proband (OR for female first-degree relative 3.23 vs. all second-degree relatives, 95% CI 1.67-6.22). CONCLUSIONS: Female first-degree relatives of patients with the long QT syndrome have a higher risk of cardiac events than male first- or second-degree relatives, independent of recorded electrocardiographic findings. Not only bradycardia, but also tachycardia increases risk of cardiac events in family members of patients with the long QT syndrome.

Adolescent↗
PubMed1995

Long QT syndrome: an indication for cervicothoracic sympathectomy.

Beta-blockade represents the primary treatment modality in patients with long QT syndrome, but left cervicothoracic sympathectomy (LCS) has been employed in refractory cases and in cases with malignant arrhythmias. LCS was performed in ten patients (six male, four female) with long QT syndrome, ranging in age from 1 month to 40 years (median 15 years). Familial long QT syndrome was present in seven patients (70%). The mean(s.e.m.) (range) preoperative corrected QT interval (QTc) was 0.52(0.01) (0.46-0.60)s. The mean(s.e.m.) duration of symptoms was 4.4(1.1) years with a mean(s.e.m.) of 4.1(0.9) syncopal episodes and 1.2(0.2) cardiac arrests per patient. LCS was carried out for refractory symptoms on beta-blockers in nine cases; a single patient was unable to tolerate beta-blockers and LCS represented the primary treatment modality. A left supraclavicular approach was utilized in each patient, resecting a portion of the stellate and all of the T2 and T3 ganglia. The median(range) length of hospitalization following operation was 2(2-6) days. There were no unexpected complications of operation, although nine (90%) of the patients developed Horner's syndrome. The QTc decreased a mean(s.e.m.) of 0.03(0.01)s following operation (P < 0.01). The frequency of symptomatic episodes decreased from a mean(s.e.m.) of 7.1(3.1)/year before LCS to 0.1(0.1) after operation (P < 0.001). Patients have been followed for a mean of 1.3(0.3) years, and all but one patient remains symptom-free; the youngest patient died suddenly 10 months after surgery. These results suggest that LCS is associated with significant clinical benefits in patients with long QT syndrome and the procedure should be considered when symptoms are refractory and malignant, or when contraindications to beta-blockers are present.

Adolescent↗
PubMed1995

Dispersion of repolarization. Relation to heart rate and repolarization duration.

Repolarization duration is highly dependent on heart rate. A major concern when evaluating dispersion of repolarization is the possible influence of heart rate on the magnitude of dispersion. Another consideration relates to a potential relationship between overall duration of repolarization and the magnitude of dispersion, that is, whether patients with longer repolarization duration present with increased or decreased dispersion of repolarization. Therefore, the following relationships were studied in 380 normal subjects, 68 coronary artery disease (CAD) patients, and 41 long QT syndrome (LQTS) patients: the magnitude of dispersion (JTd) versus cycle length (R-R) and dispersion versus repolarization duration (QTc interval). Dispersion of repolarization (JTd), measured as the maximal difference in JT interval duration between precordial leads, was significantly higher in LQTS patients than in normal subjects or CAD patients (120 +/- 72 vs 53 +/- 42 and 48 +/- 22 ms, respectively). In neither normal subjects, CAD patients, or LQTS patients were there significant relationships between the magnitude of dispersion and the R-R interval (r = .094, .158, and .233, respectively; not significant) and between the magnitude of dispersion and QTc duration (r = .0443, -.094, and .126, respectively; not significant). In normal subjects, CAD patients, and LQTS patients, the magnitude of dispersion is not significantly related to heart rate, indicating that there is no need for heart rate adjustment of dispersion parameters. In addition, there is no significant association between the magnitude of dispersion and duration of repolarization.

Adult↗
PubMed1995

Health-risk behaviors among our nation's youth: United States, 1992.

This report presents national estimates of the prevalence of selected health risk behaviors among youth ages 12-21 years, by sex, Hispanic origin, and race for youth of non-Hispanic origin. Topics include: cigarette and other tobacco use, alcohol and other drug use, sexual experience, HIV/AIDS education, runaway and homeless experiences, violence, unintentional injury control, weight control, and participation in physical activities. Data are from the 1992 National Health Interview Survey's Youth Risk Behavior Survey.

Adolescent↗
PubMed1994

Polymorphism of the gene encoding a human minimal potassium ion channel (minK).

A gene (minK) that encodes a minimal potassium channel has been cloned recently. We describe in this paper a human minK sequence which differs from the original sequence with a single A-->G at position 112. This resulted in a change from a Ser codon (AGT) to a Gly codon (GGT) and created a new MspAI restriction site. Of the 32 alleles from 16 subjects studied, 25 had this newly discovered sequence and 7 had the previously described sequence.

Alleles↗
PubMed1994

Dispersion of ventricular repolarization and arrhythmic cardiac death in coronary artery disease.

In a recent prospective study of myocardial ischemia, arrhythmic cardiac death occurred in 17 of 936 patients (2%) during a 2-year follow-up after acute myocardial infarction or unstable angina. Dispersion of ventricular repolarization was evaluated on the 12-lead electrocardiogram at enrollment in 17 patients who subsequently died of cardiac arrhythmia and in 51 matched survivors. The aim of this study was to evaluate the relation between various measurements of dispersion of repolarization and subsequent arrhythmic cardiac death, and to determine if dispersion of repolarization makes an independent contribution to the risk of arrhythmic cardiac death. Ventricular depolarization quantitated in terms of mean QRS (QRS-m) duration, and ventricular repolarization quantitated in terms of mean (m), maximal-minimal dispersion (d), standard deviation (s), and coefficient of variation (cv) of QT and JT intervals, were determined. Univariate analyses revealed that 2 standard electrocardiographic parameters, QRS-m and QT-m, and 3 dispersion variables, JT-d, JT-s, and JTc-d, were associated with arrhythmic cardiac death (p < 0.01). Multivariate analyses revealed that the combination of the dispersion parameter (JT-d, JT-s, or JTc-d) and QRS-m made an independent contribution to the risk of arrhythmic cardiac death. The findings highlight the importance of both delayed depolarization and heterogenous repolarization as risk factors for arrhythmic cardiac death. Thus, increased dispersion of repolarization is associated with an elevated likelihood of arrhythmic cardiac death. Prolonged QRS duration and increased dispersion of repolarization make independent contributions to the risk of arrhythmic cardiac death in patients with coronary artery disease.

Aged↗
PubMed1994

Relation between myocardial infarct location and stroke.

OBJECTIVES: We sought to compare the likelihood of stroke in patients with anterior versus nonanterior myocardial infarction. BACKGROUND: The association between anterior infarction and left ventricular thrombus has led to the assumption that embolization from thrombi is an important cause of stroke in patients with anterior infarction. We hypothesized that if anterior infarction is a cause of left ventricular thrombi, the number of strokes should be disproportionately higher in patients with anterior than nonanterior infarction. METHODS: We performed a retrospective analysis of 2,466 patients randomized from day 3 to day 15 after infarction as part of a multicenter placebo-controlled study of diltiazem to prevent cardiac death or myocardial infarction. Any acute focal cerebral disorder resulting in localizing findings characterized as a stroke or transient ischemic attack was considered an event. RESULTS: Of 91 events during a follow-up period of 12 to 52 months, 23 (3.2%) occurred in 724 patients with an anterior and 68 (3.9%) in 1,742 patients with a nonanterior myocardial infarction (relative risk 0.81; 95% confidence interval 0.51 to 1.30). Power analysis revealed that the negativity of the study was not the result of inadequate sample size. Life table analysis showed no difference in cumulative event rate (p = 0.42) according to site of infarction. Cox regression analysis showed that of 10 clinical covariates, only systolic blood pressure was predictive of stroke (p < 0.001). The use of warfarin did not contribute to the model. Finally, the addition of site of infarction (anterior vs. nonanterior) did not contribute significantly to the Cox model. CONCLUSIONS: Although there is a significant incidence of stroke after acute myocardial infarction, there is no relation between the occurrence of stroke and site of infarction. These data do not support the presumed causal relation between anterior myocardial infarction, thrombus and stroke.

Adult↗
PubMed1994

T wave alternans in idiopathic long QT syndrome.

OBJECTIVES: The study evaluates the association between T wave alternans and the risk of cardiac events (syncope, aborted cardiac arrest or cardiac death) in a large population of patients with idiopathic long QT syndrome. BACKGROUND: T wave alternans is an infrequently recorded electrocardiographic (ECG) finding in patients with delayed repolarization, and its clinical significance is not clear. METHODS: A total of 4,656 ECG recordings in 2,442 patients enrolled in the International Long QT Syndrome Registry were reviewed for episodes of T wave alternans. To determine the risk associated with T wave alternans, independent of corrected QT interval (QTc) duration, patients with T wave alternans were matched for QTc value (every 0.025 s1/2) to patients with long QT syndrome without T wave alternans. RESULTS: T wave alternans was identified in 30 patients (25 of whom had a QTc interval > 0.50 s1/2). A strong association between QTc prolongation and T wave alternans was observed (odds ratio 1.23 per 0.01-s1/2 unit increase in QTc, p < 0.0001). Conditional logistic regression analyses with adjustment for age, gender, status and QTc value revealed that T wave alternans did not make a significant independent contribution to the risk of cardiac events. The risk of experiencing a major cardiac event was primarily related to length of QTc. CONCLUSIONS: T wave alternans, a marker of electrical instability and regional heterogeneity of repolarization, identifies a high risk subset of patients with prolonged repolarization. Patients with T wave alternans have an increased risk of cardiac events, but this risk is primarily related to the magnitude of repolarization delay (QTc prolongation). T wave alternans does not make an independent contribution to the risk of cardiac events after adjustment for QTc length.

Adolescent↗
PubMed1994

Automatic detection of spatial and dynamic heterogeneity of repolarization.

Heterogeneity of ventricular repolarization is associated with the development of life-threatening ventricular arrhythmias. Temporal heterogeneity of repolarization may be manifest in an individual beat (spatial heterogeneity) or in a sequence of beats (dynamic heterogeneity). Spatial inhomogeneity of repolarization throughout the myocardium may be expressed electrocardiographically as dispersion of repolarization durations computed in simultaneously recorded leads. The beat-to-beat changes in the repolarization pattern (duration and/or amplitude) may account for a dynamic (time-dependent) dimension of heterogeneity, occasionally seen as T-wave alternans. A visual detection of heterogeneous repolarization is a time-consuming, observer-dependent, and frequently inaccurate process. Therefore, we developed computer algorithms designed to detect automatically (1) dispersion of repolarization and (2) nonvisible T-wave alternans from digitally recorded (1,000 Hz) X, Y, and Z electrocardiogram leads. This automatic approach was subsequently tested in 10 patients with idiopathic long QT syndrome and in 10 age-matched normal subjects. Long QT syndrome patients presented with significantly higher indices of heterogeneity in comparison with the control subjects; the dispersion of repolarization was 44 +/- 11 and 13 +/- 6 ms, respectively (P < .01), and T-wave alternans index was 0.40 +/- 0.37 and 0.03 +/- 0.06, respectively (P < .01). Simultaneous evaluation of spatial (dispersion of repolarization) and dynamic (T-wave alternans) aspects of repolarization provides new insight into heterogeneity of electrical recovery after myocardial depolarization. The automatic detection of repolarization dispersion and T-wave alternans in digital electrocardiogram recordings provides a practical method to evaluate heterogeneity of repolarization and may be useful for stratifying patients at risk of ventricular arrhythmias.

Arrhythmias, Cardiac↗