bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimated Frequency of Genetic and Nongenetic Causes of Congenital Idiopathic Cerebral Palsy in West Sweden
Authors: Costeff H.
Published: December 2004

Mathematical analysis of prenatal and perinatal risk factors was performed on the first 681 published cases of idiopathic congenital cerebral palsy (born 1959–1970) in the west Swedish population‐based cerebral palsy (CP) study. Analysis indicates that an estimated 40% of etiologically undiagnosed cases of CP in the community (48% of those born at term and 24% of those born prematurely) are genetically caused. These proportions of genetic causation are no less in CP than in idiopathic mental retardation. Genetic causes account for 60% of maturely born hemiplegics, 45% of maturely born spastic diplegics, 32% of premature spastic diplegics and virtually all cases of pure ataxia. About 23% of CP cases in the community have suffered nongenetic brain damage in accordance with the two‐stage model. The residue of 37% is characterized by a single risk factor, usually perinatal.
Commingling Analysis of Intraocular Pressure and Glaucoma in an Older Australian Population
Authors: Viswanathan Ananth C. , Hitchings Roger A. , Indar Andrea , Mitchell Paul , Healey Paul R. , McGuffin Peter , Sham Pak C.
Published: December 2004

Purpose: To test the hypothesis of a major genetic determinant of intraocular pressure (IOP) under the mixed genetic model in a defined population, and to elucidate the relationship between IOP and glaucoma.

Methods: IOP was measured in 3654 persons attending the Blue Mountains Eye Study. A commingling analysis on IOP was performed using a new program, SKUDRIVER. The goodness of fit of 1‐, 2‐ and 3‐distribution models was measured. This was repeated after the glaucoma cases had been removed from the dataset, and further repeated on the glaucoma cases in the dataset.

Results: The best model was 3‐distribution with no evidence for Hardy‐Weinberg disequilibrium. The proportion of variance explained by this major effect was 0.18. When glaucoma cases were removed, the best model had 2 distributions. There was no evidence of admixture in glaucoma patients.

Conclusions: The findings of this study are consistent with the presence of a major gene accounting for 18% of the variance of IOP, which could therefore influence the risk of glaucoma, in this population. These findings suggest methods of optimizing strategies for family and association studies to identify quantitative trait loci for IOP. No evidence for distinct IOP‐dependent and IOP‐independent subgroups of glaucoma was found.
Exploration of Multilocus Effects in a Highly Polymorphic Gene, the Apolipoprotein (APOB) Gene, in Relation to Plasma apoB Levels
Authors: Tahri‐Daizadeh N. , Tregouet D. A. , Nicaud V. , Poirier O. , Cambien F. , Tiret L.
Published: December 2004

A detailed exploration of all the polymorphisms in candidate genes is required to better characterize the relationship between gene variability and complex traits. We propose a novel strategy for investigating the association between a highly polymorphic gene and a phenotype, by combining a multilocus genotype analysis and an haplotype analysis. For the multilocus genotype analysis, a data mining tool ‐ termed DICE (Detection of Informative Combined Effects) – was developed to identify the best subset of polymorphisms that are associated ‐ individually or in combination – with the phenotype. For the haplotype analysis, we used our recently developed method of haplotype‐phenotype association to determine the most informative and parsimonious haplotype model fitting the data. We illustrate this strategy by investigating the association between twelve polymorphisms of the APOB gene and plasma apoB levels in 1442 European subjects. After exploring all main effects and interactions between polymorphisms, DICE identified the N4311S polymorphism as the most informative polymorphism in relation to apoB levels. Haplotype analysis led to the same conclusion. Additionally, DICE identified the E4154K (EcoRI) and the T2488T (XbaI) polymorphisms as potentially interesting. This selection was not modified by inclusion of the common APOE polymorphism in the analysis.
Mitochondrial DNA Diversity in Tribal and Caste Groups of Maharashtra (India) and its Implication on Their Genetic Origins
Authors: Baig M. M. , Khan A. A. , Kulkarni K. M.
Published: December 2004

Genetic relationships among caste‐groups are not uniform across the geographical regions of India. Many anthropologists have speculated on the tribal origin of some caste groups in Maharashtra and other states of India. To test this hypothesis, we used neutral mtDNA markers to study genetic relatedness among tribal and caste groups from Maharashtra. Descriptive statistics such as nucleotide diversity, gene diversity and average mismatches were found to be of the same magnitude. Phylogenetic network analysis exhibited a star‐like expansion that may date back to the peopling of Eurasia, ∼50,000 year ago. The reconstruction of mtDNA haplogroups showed that both the caste and tribal populations share similar branches of the tree. Also, the coalescence age estimation of caste and tribal populations suggests the persistence of maternal lineages with their root in early late Pleistocene. Our mtDNA analyses show some preliminary and significant evidence for the origin of prehistoric tribal and hierarchical caste societies of Maharashtra.
Inferring the Most Likely Geographical Origin of mtDNA Sequence Profiles
Authors: Egeland T. , Bøvelstad H.M. , Storvik G.O. , Salas A.
Published: December 2004

In a number of practical cases it is important to determine the likely geographical origin of an individual or a biological sample. A dead body, old bones or a sample of semen may be available. Information on where the sample might come from can assist investigation or research. The first part of this paper is independent of specific data structure. We formulate the problem as a classification problem. Bayes' theorem allows different sources of information or data to be reconciled conveniently. The main part of the paper involves high dimensional data for which simple, standard methods are not likely to work properly. Mitochondrial DNA (mtDNA) data is a typical example of such data. We propose a procedure involving essentially two steps. First, principal component analysis is used to reduce the dimension of the data. Next, quadratic discriminant analysis performs the actual classification. A cross validation procedure is implemented to select the optimal number of principal components. The importance of using separate data sets for model fitting and testing is emphasized. This method distinguishes well between individuals with a self reported European (Icelandic or German) origin and SE Africans. In this case the error rate is 2.0%.
The FBN1 (R2726W) mutation is not fully penetrant
Authors: Buoni S. , Zannolli R. , Macucci F. , Ansaldi S. , Grasso M. , Arbustini E. , Fois A.
Published: December 2004

The R2726W mutation in the fibrillin 1 (FBN1, Marfan syndrome) gene segregates with isolated skeletal features of Marfan syndrome and/or high stature. Here we report a family in which two out of four individuals, an 18‐year‐old son and his mother, a 41‐year‐old woman, had the R2726W mutation of FBN1. Both family members carrying the mutation were of average height. The son had a Marfan‐like phenotype, but his mother did not. The FBN1 R2776W mutation, which is associated with skeletal features of Marfan syndrome, appears incompletely penetrant. Consequently, genetic counselling in the presence of this mutation is difficult.
Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus
Authors: Giardina E. , Capon F. , De Rosa MC. , Mango R. , Zambruno G. , Orecchia A. , Chimenti S. , Giardina B. , Novelli G.
Published: December 2004

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Non‐parametric linkage analyses have mapped many susceptibility loci on different chromosomes. We mapped one of these loci, PSORS4, on human chromosome 1q21. Using the linkage disequilibrium approach, we refined the critical region to a specific genomic interval of about 100 Kb which contains only the loricrin (LOR) gene. Here we report a genetic and functional study of this gene to verify its involvement in psoriasis pathogenesis. We document low expression of LOR in psoriatic skin of patients selected from families in which the disease was segregrating with the PSORS4 locus. Re‐sequencing of the entire gene in a subset of patients revealed the existence of novel polymorphisms able to influence the protein structure, as shown by molecular modelling studies. However, no evidence for genetic association was detected in a large cohort of Italian nuclear families. This rules out the LOR gene as a candidate for the PSORS4 locus.
Replication in genetic studies of complex traits
Authors: Sillanpää Mikko J. , Auranen Kari
Published: December 2004

Disappointments in replicating initial findings in gene mapping for complex traits are often attributed to small sample sizes and inadequate techniques to determine the threshold value. This is clearly not the whole truth. More fundamental reasons lie in the inherent heterogeneity related to disease, including genetic heterogeneity, differences in allele frequencies, and context‐dependency in genetic architecture. There are also other reasons related to the data collection and analysis. Replication may remain a source of frustration unless more emphasis is put on controlling these sources of heterogeneity between studies.
Power of Variance Component Linkage Analysis—II. Discrete Traits
Authors: WILLIAMS J. T. , BLANGERO J.
Published: December 2004

We determine the power of variance component linkage analysis in the case of discrete, dichotomous traits analyzed under a classical liability threshold model. For simplicity we consider randomly ascertained samples and an additive model of variation incorporating a qtl, residual additive genetic factors, and individual‐specific random environmental effects. We derive an expression for the power of variance component linkage analysis in arbitrary relative pairs, and compare the power of discrete and quantitative trait linkage analysis in the specific case of sibpairs. The predicted sample sizes required in linkage analysis of sibpairs are confirmed by analysis of simulated data. Unlike the affected‐sibpair method, the power of discrete trait variance component analysis increases with trait prevalence. The relative efficiency of a discrete trait for linkage analysis increases with population trait prevalence, but does not exceed about 40% and is typically much less.
Genetic Evidence Concerning the Origins of South and North Ossetians
Authors: Nasidze Ivan , Quinque Dominique , Dupanloup Isabelle , Rychkov Sergey , Naumova Oksana , Zhukova Olga , Stoneking Mark
Published: December 2004

Ossetians are a unique group in the Caucasus, in that they are the only ethnic group found on both the north and south slopes of the Caucasus, and moreover they speak an Indo‐European language in contrast to their Caucasian‐speaking neighbours. We analyzed mtDNA HV1 sequences, Y chromosome binary genetic markers, and Y chromosome short tandem repeat (Y‐STR) variability in three North Ossetian groups and compared these data to published data for two additional North Ossetian groups and for South Ossetians. The mtDNA data suggest a common origin for North and South Ossetians, whereas the Y‐haplogroup data indicate that North Ossetians are more similar to other North Caucasian groups, and South Ossetians are more similar to other South Caucasian groups, than to each other. Also, with respect to mtDNA, Ossetians are significantly more similar to Iranian groups than to Caucasian groups. We suggest that a common origin of Ossetians from Iran, followed by subsequent male‐mediated migrations from their Caucasian neighbours, is the most likely explanation for these results. Thus, genetic studies of such complex and multiple migrations as the Ossetians can provide additional insights into the circumstances surrounding such migrations.
Susceptibility to Basal Cell Carcinoma: Associations with PTCH Polymorphisms
Authors: Strange R. C. , El‐Genidy N. , Ramachandran S. , Lovatt T. J. , Fryer A. A. , Smith A. G. , Lear J. T. , Wong C. , Jones P. W. , Ichii‐Jones F. , Hoban P. R.
Published: December 2004

Loss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2318, 3429, 111552, 121665, 121686, 142199 and 233944 and intron 91336‐135 and 152560+9PTCH variants were sufficiently common for use in case‐control studies, and if selected markers were associated with risk. Intron 152560+9 and exon 233944 variants were studied further. Their genotype frequencies were not significantly different in controls and cases, though frequency of the G2560+9‐C3944 haplotype was lower in all cases (odds ratio = 0.44, p = 0.009) and those stratified by BCC site and rate of development of further tumours. This association was not mediated by the extent of UVR exposure. We confirmed the robustness of these findings by showing these associations demonstrated similar odds ratios in two groups of randomly selected cases and controls, and using the false positive report probability (FPRP) approach described by Wacholder et al. (2004). The FPRP value (0.168) was in the noteworthy category. These data, showing for the first time that PTCH polymorphism mediates susceptibility, are compatible with reports showing that PTCH haploinsufficiency influences development of BCC precursor lesions.
Correlation Between the Allelic Distribution of STRs in a Finnish Population and Phenotypically Different Gastrointestinal Tumours: A Study Using Four X‐Chromosomal Markers (DXS7423, DXS8377, ARA, DXS101)
Authors: Vauhkonen H. , Vauhkonen M. , Sipponen P. , Sajantila A.
Published: December 2004

Microsatellite instability in tumours has been suggested as a model to study the process of short tandem repeat (STR) mutations. In the present study we have determined the allelic variation of four X‐STRs (DXS7423, DXS8377, DXS101 and ARA) in a Finnish population of 103 individuals, and assessed whether a comparable allelic distribution could be found in a series of gastrointestinal cancers differing by the level of microsatellite instability. Fifty‐seven gastric and colorectal cancers were stratified by autosomal STRs, and the mononucleotide marker BAT‐26 into stable, low‐level unstable and high‐level unstable microsatellite (MSI‐H) cancers, of which the last produced the majority of X‐STR alleles. For the four markers analysed, a significant correlation of allele distribution between our Finnish population sample and MSI‐H tumours was noted. Together, the eight MSI‐H tumours found represented 80%, 66–80% and 100% of the DXS101 alleles in the Finnish, and in previously described Caucasian and Korean population samples, respectively. Of the ARA, DXS7423 and DXS8377 alleles in the Finnish population, 42%, 75% and 79% were found in the MSI‐H cancers, respectively. The results suggest that analysis of STR variation in a relatively small number of MSI‐H cancers may aid in pre‐evaluation of their allelic distribution in a population.
White Blood Cell Count and the Occurrence of Silent Ischemia after Myocardial Infarction
Authors: Kurpesa Małgorzata , Trzos Ewa , Krzemińska‐Pakuła Maria
Published: December 2004

Background: Inflammation plays a role in the pathogenesis of atherosclerosis. Attempts are made to use markers of inflammation as prognostic factors in coronary artery disease and acute coronary syndromes. The correlation between inflammation and silent postinfarction ischemia is unknown.

Methods: The study population consists of 104 asymptomatic patients who had uncomplicated Q‐wave myocardial infarction within 6 months prior to the enrollment. After the white blood cell (WBC) count was assessed, the population was divided into two groups: group I comprising 48 patients with WBC ≤ 7.0 × 103/μl and group II comprising 56 patients with WBC > 7.0 × 103/μl. Twenty‐four‐hour Holter monitoring was performed to detect the presence of silent ischemia.

Results: Eighty‐eight silent ischemic episodes were recorded. Ischemia on Holter monitoring was detected in 47 patients (84%) from group II and in five patients (9%) in group I (P < 0.01). We have found a significant positive correlation between WBC count and the number of ischemic episodes (r = 0.25), their maximal amplitude (r = 0.39), duration (r = 0.34), and total ischemic burden (r = 0.36). In multivariate analysis leucocytosis proved to be the only parameter independently correlated with the presence of silent ischemia.

Conclusion: Postinfarction asymptomatic patients with increased WBC count are more likely to have residual ischemia.
Seasonal Variability of QT Dispersion in Healthy Young Males
Authors: Kose Sedat , Aytemir Kudret , Can Ilknur , Iyisoy Atilla , Kursaklioglu Hurkan , Amasyali Basri , Kilic Ayhan , Isik Ersoy , Oto Ali , Demirtas Ertan
Published: December 2004

Background: There are few data related to the seasonal influences on the QT dispersion.

Methods: We analyzed the effects of seasons on QT dispersion in a large group of healthy young males. We studied the seasonal variability of QT dispersion in 523 healthy male subjects aged 22 ± 4 years (ranging from 20 to 26). Four seasonal 12‐lead resting electrocardiograms (ECGs) recorded at double amplitude were performed at 25 mm/s at intervals of 3 months. Subsequent ECGs were recorded within 1 hour of the reference winter recording. QT dispersion was defined as the difference between the longest and the shortest mean QT intervals.

Results: There was a significant seasonal variation in QT dispersion (P = 0.001), with the largest QT dispersion in winter (71 ± 18 ms) and the smallest one in spring (43 ± 19).

Conclusion: There exists a significant seasonal variation in QT dispersion of healthy subjects and such variability should be taken into consideration in the evaluation process of QT dispersion.
Sildenafil Citrate Does Not Affect QT Intervals and QT Dispersion: An Important Observation for Drug Safety
Authors: Alpaslan Mete , Onrat Ersel , Samli Murat , Dincel Cetin
Published: December 2004

Background: Sildenafil is an effective and widely used therapeutic agent for erectile dysfunction. Deaths have been reported due to sildenafil use and most of them are attributed to concurrent use of nitrates. However, the effects of sildenafil on QT intervals, QT dispersion, and the possible risk of ventricular arrhythmia have not been studied before. Our aim in this study was to evaluate the effect of sildenafil citrate on QT intervals and QT dispersion.

Methods: Thirty‐six patients with erectile dysfunction were included in this study. Twenty‐one patients had coronary artery disease whereas 12 of them also had accompanying diabetes mellitus. Standard 12‐lead electrocardiograms (ECG) were recorded three times: before, and at the first and fourth hours of 50 mg sildenafil citrate ingestion. All QT parameters were corrected for heart rate.

Results: Mean age of the patients was 54 ± 12 years. The mean heart rate did not differ significantly between the three ECG examinations. The corrected and uncorrected maximum and minimum QT intervals were not significantly different between the three ECG examinations. The QT dispersion and corrected QT dispersion before and 1 hour and 4 hours after sildenafil ingestion were 31 ± 9 ms, 36 ± 10 ms; 32 ± 11 ms, 37 ± 14 ms; 27 ± 8 ms, 32 ± 9 ms, respectively (P > 0.05).

Conclusions: Sildenafil does not prolong QT intervals or increase QT dispersion in patients with erectile dysfunction. Our results suggest that the risk of ventricular arrhythmia does not increase with ingestion of 50 mg sildenafil.
Increased P‐Wave Duration and P‐Wave Dispersion in Patients with Aortic Stenosis
Authors: Turhan Hasan , Yetkin Ertan , Atak Ramazan , Altinok Tayfun , Senen Kubilay , Ileri Mehmet , Sasmaz Hatice , Cehreli Sengul , Kutuk Emine
Published: December 2004

Background: P‐wave dispersion (PWD), defined as the difference between the maximum and minimum P‐wave duration, has been proposed as being useful for the prediction of paroxysmal atrial fibrillation (AF). AF is the most common arrhythmia and an important prognostic indicator for clinical deterioration in patients with aortic stenosis (AS). The aim of the present study was to evaluate PWD in patients with AS.

Methods: The study population consisted of two groups: Group I consisted of 98 patients with AS (76 men, 22 women; aged 63 ± 8 years) and group II consisted of 98 healthy subjects (same age and sex) without any cardiovascular disease. A 12‐lead electrocardiogram was recorded for each subject. The P‐wave duration was calculated in all leads of the surface electrocardiogram. The difference between the maximum and minimum P‐wave duration was calculated and was defined as the PWD. All patients and control subjects were also evaluated by echocardiography to measure the left atrial diameter, left ventricular ejection fraction, left ventricular wall thicknesses, and the maximum and mean aortic gradients. Patients were also evaluated for the presence of paroxysmal AF.

Results: Maximum P‐wave duration and PWD of group I were found to be significantly higher than those of group II. In addition, patients with paroxysmal AF had significantly higher PWD than those without paroxysmal AF. There was no significant difference between the two groups regarding minimum P‐wave duration. In addition, there was no significant correlation between echocardiographic variables and PWD.

Conclusion: PWD, indicating increased risk for paroxysmal AF, was found to be significantly higher in patients with AS than in those without it. Further assessment of the clinical utility of PWD for the prediction of paroxysmal AF in patients with severe AS will require longer prospective studies.
The Relation of QT Dispersion and Localized QT Difference to Coronary Pathology in a Population with Unstable Coronary Artery Disease
Authors: Kesek Milos , Englund Anders , Jernberg Tomas , Lagerqvist Bo , Lindahl Bertil
Published: December 2004

Background: QT dispersion (QTd) contains prognostic information in several patient groups. The variable increases in several conditions with ischemia. Originally, it was thought to reflect the local repolarization inhomogeneity. Even though this explanation has been questioned lately, it continues to be put forward. In order to elucidate a possible local mechanism, we investigated the relation between QT dispersion, an ECG parameter reflecting the local dispersion, and angiographical measures in a population with unstable coronary artery disease.

Methods: The 276 patients were recruited from the FRISC II trial. As the QTd parameter we used the mean value of automatically measured QTd during 27 hours after admission (QTdMean). As a local repolarization measure we used the maximal difference in QT between two adjacent ECG leads (QTdiffMean). The computations were performed on all available ECG leads and on a restricted set without the V1–V2 combination. Previously published angiographic scoring tools were adapted for rating and localizing the coronary pathology by two approaches and applied on 174 patients undergoing angiography.

Results: QTdMean was significantly higher than that reported in previous material with unselected chest pain patients (55 vs 40 ms). QTdiffMean correlated strongly with QTdMean. No differences in QTdMean were detected between patients with different angiographical scores. No relation could be shown between the region with dominating coronary pathology as expressed by the scoring tools and the localization of QTdiffMean.

Conclusions: QTd in ischemia seems to be increased by a mechanism unrelated to localization and severity of coronary disease.
Relationship Between ST‐Segment Morphology and Conduction Disturbances Detected by Signal‐Averaged Electrocardiography in Brugada Syndrome
Authors: Takami Mitsuaki , Ikeda Takanori , Enjoji Yoshihisa , Sugi Kaoru
Published: December 2004

Background: Although arrhythmogenesis of Brugada syndrome is still unknown, it has been reported to be associated with conduction disturbances. Two ST‐segment morphologies (coved and saddle‐back patterns) have been described in this syndrome. No study has sought to determine which morphology has stronger conduction disturbances, thereby associating with life‐threatening events.

Methods: Forty‐six patients who presented the Brugada‐type ECG with either of a characteristic coved (n = 25) or saddle‐back (n = 21) pattern of ST‐segment morphology underwent signal‐averaged ECG (SAECG). SAECG parameters, and the history of life‐threatening events defined as syncope or aborted sudden death, were compared between groups.

Results: Although filtered QRS duration did not differ between groups, the incidence of late potentials in the coved group was higher than in the saddle‐back group (22 patients (88%) versus 4 patients (19%); P < 0.01), showing lower RMS40 and longer LAS40. Life‐threatening events occurred in 17 patients (68%) in the coved group and 7 patients (33%) in the saddle‐back group (P = 0.02).

Conclusion: The coved pattern of ST segment was more closely related to conduction disturbances than the saddle‐back pattern in patients with Brugada‐type ECG. Life‐threatening events were more common in patients with the coved ST‐segment elevation. Conduction disturbances in the coved pattern of ST segment may reflect a substrate of arrhythmogenesis in Brugada syndrome.
Prevalence of Potential Noninvasive Arrhythmia Risk Predictors in Healthy, Middle‐Aged Persons
Authors: Grimm Wolfram , Liedtke Julia , Müller Hans‐Helge
Published: December 2004

Background: To date, prevalence and clinical significance of noninvasive arrhythmia risk predictors in apparently healthy, middle‐aged persons are largely unknown.

Methods: A total of 110 apparently healthy persons 20–75 years old were enrolled in this prospective observational monocenter study and followed up for 32 ± 15 months. Baseline investigations included symptom‐limited bicycle ergometry, echocardiography, time‐domain analysis, and spectral turbulence analysis of the signal‐averaged electrocardiogram (ECG), ventricular arrhythmias, and heart rate variability on 24‐hour Holter ECG, baroreflex sensitivity, and t‐wave alternans in all persons.

Results: The prevalence of an abnormal signal‐averaged ECG was 1% for spectral turbulence analysis and varied between 1% and 37% for time‐domain analysis depending upon the definition used for an abnormal time‐domain analysis. A reduced heart rate variability defined as a standard deviation of normal‐to‐normal intervals ≤105 ms, <100 ms and <70 ms was found in 12%, 9%, and 1% of persons. A baroreflex sensitivity <6 ms/mmHg and <3 ms/mmHg was present in 15% and 2% of persons. Microvolt t‐wave alternans was found to be positive in 5%, negative in 88%, and indeterminate in 7% of persons, respectively. During the 32 ± 15 months follow‐up, no arrhythmic events and no cardiovascular mortality were observed in this population.

Conclusions: Abnormal findings of noninvasive arrhythmia risk stratification can be found in 1–37% of healthy, middle‐aged persons when previously reported cut‐off values are used.
Long‐Term Improvement of QT Dispersion is Unaffected by Short‐Term Changes in Blood Pressure During Treatment of Systemic Hypertension with Enalapril
Authors: Seara Francisco Javier García , Juanatey José Ramón González , Sande José Luis Martínez , Veloso Pedro Rigueiro , Reino Antonio Pose , Román Alfonso Varela , Cerrato José Cabezas , Peña Miguel Gil de la
Published: December 2004

Background: We report the reduction of QT and QTc dispersion in patients treated for 7 years with enalapril for systemic hypertension with left ventricular (LV) hypertrophy. We assess the correlation between QT dispersion and LV mass during this period and at the end of an 8‐week period of suspension of enalapril treatment after 5 years.

Methods: Twenty‐four previously untreated patients with this condition took enalapril (20 mg twice daily) for 7 years, except during an 8‐week period following 5‐year follow‐up. Cardiovascular parameters were determined by two‐dimensional guided M‐mode echocardiography, and QT interval was measured, in a pretreatment placebo phase, 8 weeks and 1, 3, 5, and 7 years after the start of the therapy, at the end of the 8‐week suspension effected after 5 years, and 8 weeks after the end of the suspension.

Results: Therapy rapidly reduced blood pressure (BP) from 156/105 mmHg to normal values: 134/84 mmHg after 8 weeks’ treatment, 130–84 mmHg at 7‐year follow‐up (P < 0.001 with respect to the placebo phase). LV mass index decreased progressively until at 5‐year follow‐up the reduction had reached 39% (P < 0.001), after which neither LV mass nor any other structural parameter underwent any further significant change. During this time, QT dispersion (ΔQT) and the dispersion of “corrected” QT (ΔQTc) decreased significantly: ΔQT (from 61 ± 21 to 37 ± 13 ms) and ΔQTc (from 67 ± 27 to 41 ± 16 ms). After suspension of treatment for 8 weeks following 5‐year follow‐up, ΔQT was 40 ± 14 ms and ΔQTc was 44 ± 17 ms; there were no significant changes either in ΔQT and ΔQTc or LV hypertrophy although BP had returned to pretreatment values (BP: 150 ± 16; 101 ± 10 mmHg).

Conclusions: Long‐term enalapril treatment of hypertensive patients with LV hypertrophy induces marked regression of LV mass and improvement of QT dispersion. These improvements occur on a longer timescale than improvement in BP, and are not affected by transient changes in BP values.
Testing of a New T‐Wave Subtraction Algorithm as an Aid to Localizing Ectopic Atrial Beats
Authors: Marenco John P. , Nakagawa Hiroshi , Yang Shawn , MacAdam David , Xu Lucien , He Ding S. , Link Mark S. , Homoud Munther K. , Estes III N.A. Mark , Wang Paul J.
Published: December 2004

Background: Identifying the timing and morphology of an ectopic P wave from the surface electrogram can aid in the diagnosis and localization of atrial arrhythmias. Given the relatively short coupling interval of atrial ectopic beats, the P wave is often obscured by the larger amplitude QRS‐T wave complex. A method to uncover such “buried” P waves using a standard 12‐lead surface ECG would be clinically useful and could potentially be a noninvasive guide to catheter ablation of focal atrial tachycardia.

Methods: We developed an automated computerized program (BARD DUO LAB SYSTEM™) designed to subtract the QRS‐T wave complex from the surface electrogram and uncover a previously obscured P wave. The purpose of the present study was to validate this program. The surface ECG from 21 patients undergoing atrial pacing during electrophysiologic study (group I) and 10 patients with atrial tachycardia (group II) were analyzed and the derived P‐wave morphology assessed using correlation waveform analysis (CWA) and visual grading by three reviewers.

Results: The algorithm successfully uncovered the P wave in each surface ECG. For the 21 patients in group I, average CWA comparing the derived P wave with the previous paced P wave was 83%. Average CWA for group II was 82%. Visual grading of the match between derived P waves and paced P waves revealed a 21/21 match in group I patients and a 12/12 match in 9/10 of group II patients.

Conclusions: An ectopic atrial P wave obscured by a coincident QRS‐T wave complex can be accurately uncovered using this new algorithm. Addition of this technique to existing methods may improve the diagnosis of atrial arrhythmias and aid in the localization and ablation of ectopic atrial foci.
The Predictive Value of Exercise QRS Duration Changes for Post‐PTCA Coronary Events
Authors: Efrati Shai , Cantor Angel , Goldfarb Benjamin , Ilia Reuben
Published: December 2004

Background: The sensitivity and predictive values of exercise ECG testing using ST‐T criteria after percutaneous transluminal coronary angioplasty (PTCA) are low, precluding its routine use for screening for restenosis. The predictive value of QRS duration criteria during exercise testing (ET) ECG after PTCA for future coronary events has not been reported. The aim of the study was to compare QRS duration changes with ST‐T criteria during ET, as a predictor of coronary events after PTCA.

Methods: A prospective study of 206 consecutive patients who underwent ET at a mean of 34 ± 14 days after their first PTCA, and were the followed for a mean of 23 ± 9 months. Patients were divided by QRS duration into two groups—Q1: ischemic response (QRS duration prolongation of more than 3 ms relative to the resting duration), and Q2: normal response (QRS duration shortening or without change from resting duration). Patients were also divided by their ST‐T response, S1: ischemic response, and S2: normal response.

Results: During follow‐up 52 patients (58%) experienced restenosis or MI, or underwent CABG—Q1: 44 (85%), Q2: 8(15%) (P < 0.0002), S1: 8 (15%), S2: 44 (85%), (P < 0.641), two patients died—Q1: 1 (1%) and Q2: 1 (1%). For QRS and ST‐T, the relative risk of having at least one of the coronary events was 4.02 (CI 2.1–9.9) versus 1.13 (CI 0.8–2.9), respectively. The sensitivity for future coronary events was 85% and 52% and the specificity was 48% and 98% for the QRS and ST‐T criteria, respectively.

Conclusion: QRS prolongation during peak ET ECG after PTCA is a more sensitive marker than ST‐T criteria for detection of patients at risk for later coronary events.
Usefulness of Risk Stratification for Future Cardiac Events in Infarct Survivors with Severely Depressed Versus Near‐Normal Left Ventricular Function: Results From a Prospective Long‐Term Follow‐Up Study
Authors: Klingenheben Thomas , Hohnloser Stefan H.
Published: December 2004

Background: Although primary preventive therapy with implantable cardioverter defibrillators has recently been shown to be effective in patients with coronary artery disease and left ventricular dysfunction, further identification of patients at particularly high risk for arrhythmic death would improve the cost effectiveness of device therapy. The value of risk stratification in postinfarction patients with versus those without left ventricular dysfunction has not been investigated in detail in infarct survivors treated according to contemporary therapeutic guidelines.

Methods: Patients with acute myocardial infarction underwent coronary angiography including left ventricular angiography in an attempt to restore antegrade flow of the infarct‐related artery. Additionally, patients underwent noninvasive autonomic risk stratification by means of heart rate variability (HRV) and baroreflex sensitivity (BRS) measurements prior to hospital discharge.

Results: A total of 411 patients were prospectively included in the study. The primary study endpoint of cardiac death and arrhythmic events was significantly more common in patients with LVEF ≤ 35% as compared to those with preserved LV function (27% vs 4%; P < 0.0001). In patients with LV dysfunction, HRV and BRS were significant risk predictors on univariate (P < 0.01 for BRS; P = 0.04 for HRV) and multivariate (P = 0.028 for BRS; P = 0.053 for HRV) analyses. In contrast, in patients with preserved LV function, only patency of the infarct artery but not autonomic markers was significantly predictive of cardiac death and arrhythmic events.

Conclusion: The present study demonstrates that autonomic testing does not yield predictive power in infarct survivors with preserved left ventricular function. Accordingly, cost effectiveness of risk stratification and subsequent preventive therapy may be improved by restricting risk stratification to patients with impaired LV function.
Sympathetic Nervous System Activity and Ventricular Tachyarrhythmias: Recent Advances
Authors: Anderson Kelley P.
Published: December 2004

Sympathetic nervous system activity (SNSA) is believed to participate in the genesis of ventricular tachyarrhythmias (VTA) but understanding has been impeded by the number and complexity of effects and the paucity of data from humans. New information from studies of genetic disorders, animal models, and spontaneous human arrhythmias indicates the importance of the temporal pattern of SNSA in arrhythmia development. The proarrhythmic effects of short‐term elevations of SNSA are exemplified by genetic disorders and include enhancement of early and delayed afterdepolarizations and increased dispersion of repolarization. The role of long‐term elevations of SNSA is suggested by animal models of enhanced SNSA signaling that results in apoptosis, hypertrophy, and fibrosis, and sympathetic nerve sprouting caused by infusion of nerve growth factor. Processes that overlap short‐ and long‐term effects are suggested by changes in R‐R interval variability (RRV) that precede VTA in patients by several hours. SNSA‐mediated alterations in gene expression of ion channels may account for some intermediate‐term effects. The propensity for VTA is highest when short‐, intermediate, and long‐term changes are superimposed. Because the proarrhythmic effects are related to the duration and intensity of SNSA, normal regulatory processes such as parasympathetic activity that inhibits SNSA, and oscillations that continuously vary the intensity of SNSA may provide vital antiarrhythmic protection that is lost in severe heart failure and other disorders. These observations may have therapeutic implications. The recommended use of β‐adrenergic receptor blockers to achieve a constant level of inhibition does not take into account the temporal patterns and regional heterogeneity of SNSA, the proarrhythmic effects of α‐adrenergic receptor stimulation, or the potential proarrhythmic effects of β‐adrenergic receptor blockade. Further research is needed to determine if other approaches to SNSA modulation can enhance the antiarrhythmic effects.
Effects of P‐wave Dispersion on Atrial Fibrillation in Patients with Acute Anterior Wall Myocardial Infarction
Authors: Baykan Merih , Çelik Şükrü , Erdöl Cevdet , Durmuş İsmet , Örem Cihan , Küçükosmanoğlu Mehmet , Yilmaz Remzi
Published: December 2004

Backround: P‐wave dispersion (P dispersion), defined as the difference between the maximum and the minimum P‐wave duration (P minimum), and maximum P‐wave duration (P maximum) have been used to evaluate the discontinuous propagation of sinus impulse and the prolongation of atrial conduction time respectively. The aim of this study was to investigate whether early assessment of P dispersion predicts paroxysmal atrial fibrillation (AF) in patients with acute anterior wall myocardial infarction (MI).

Methods: We prospectively evaluated 147 consecutive patients (45 women, 102 men; aged 55 ± 9 years) with a first acute anterior wall MI. All patients were evaluated by echocardiography to measure the left atrial diameter and left ventricular ejection fraction (LVEF). Electrocardiography was recorded from all patients on admission and every day during hospitalization.

Results: AF occurred in 25 patients. In 122 patients, AF did not occur. P maximum was found to be significantly higher in patients with AF than in patients without AF (115 ± 17.3 ms vs 101 ± 14.7 ms, P = 0.001). P dispersion also was significantly higher in patients with AF than in patients without AF (50 ± 12.5 ms vs 43 ± 10.1 ms, P = 0.01). There was no significant difference between the two groups in P minimum (64 ± 12.5 ms vs 59 ± 11.7 ms, P = 0.057). The echocardiographically left atrial diameters were not significantly higher in the patients with AF than those without (25 ± 3.38 mm and 23 ± 3.36 mm, respectively, P = 0.76). LVEF was found to be significantly different in the patients who developed AF and in those who did not (37.96 ± 6.18% vs 47.70 ± 6.01%, P = 0.0001).

Conclusions: Although P maximum and P dispersion are significant predictive factors of AF in patients with acute anterior wall MI in the univariate analysis, on the basis of multivariate analysis, only age and LVEF were independent predictive parameters for AF.
Effects of Slow Coronary Artery Flow on QT Interval Duration and Dispersion
Authors: Atak Ramazan , Turhan Hasan , Sezgin Alpay T , Yetkin Ozkan , Senen Kubilay , Ileri Mehmet , Sahin Onur , Karabal Orhan , Yetkin Ertan , Kutuk Emine , Demirkan Deniz
Published: December 2004

Background: The coronary slow‐flow phenomenon is an angiographic phenomenon characterized by delayed opacification of vessels in the absence of any evidence of obstructive epicardial coronary disease. Several studies have demonstrated myocardial ischemia in patients with slow coronary artery flow. In the present study, we aimed at evaluating the effects of slow coronary artery flow on QT interval duration and QT dispersion as a possible indicator of increased risk for ventricular arrhythmias and sudden cardiac death.

Methods: The study population included 49 patients with angiographically proven normal coronary arteries and slow coronary flow in all three coronary vessels (group I, 33 males, 16 females, mean age = 48 ± 9 years), and 71 patients with angiographically proven normal coronary arteries without associated slow coronary flow (group II, 47 males, 24 females, mean age = 50 ± 8 years). Coronary flow rates of all subjects were documented by thrombolysis in myocardial infarction frame count (TIMI frame count). QT interval duration and QT dispersion of all subjects were measured on the standard 12‐lead electrocardiogram.

Results: There was no statistically significant difference between the two groups in respect to age, gender, presence of hypertension, and diabetes mellitus. There was a significant difference between the two groups in respect to the presence of cigarette smoking, typical angina, and positive exercise test results. TIMI frame counts of group I patients were significantly higher than those of group II patients for all three coronary arteries (P < 0.001). Maximum corrected QT interval (QTcmax) of group I did not differ from the QTcmax of group II (P > 0.05). However, minimum corrected QT interval (QTcmin) of group I was significantly lower than that for group II (P = 0.008). Consequently, corrected QT dispersion (QTcd) in group I was found to be significantly higher than in group II (P < 0.001).

Conclusion: QTcd, indicating increased risk for ventricular arrhythmias and cardiovascular mortality, was found to be significantly higher in patients with slow coronary artery flow. However, further long‐term prospective studies should be carried out to establish the significance of QTcd as a risk factor for ventricular arrhythmias and subsequent sudden cardiac death in patients with slow coronary artery flow.
Utility of SAECG in Arrhythmogenic Right Ventricle Dysplasia
Authors: Nasir Khurram , Rutberg M.P.H., Julie , Tandri Harikrishna , Berger Ronald , Tomaselli Gordon , Calkins Hugh
Published: December 2004

Background: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by progressive replacement of RV myocardium with fibro‐adipose tissue thought to be responsible for the presence of late potentials (LP) detected by SAECG. The general consensus on the role of SAECG in the diagnosis and prognosis of patients with ARVD is lacking. The purpose of this systematic review was to better define the role of SAECG in ARVD.

Methods: An extensive review of literature was done to specifically describe the prevalence of LP in ARVD and its determinants, explore the various options available to improve the diagnostic ability of SAECG, and provide recommendations for proper utilization of this technique.

Results: LPs are frequent in ARVD (47–100%), and more prevalent in severe disease and in patients with documented spontaneous VT. SAECG is a useful test in following the characteristic evolutivity of the disease. 4–16% of normal family members of patients with ARVD also have abnormal SAECG results. Detection of LP in ARVD can be improved by employing a high‐pass filter of 25 Hz and specifically looking for changes in the Z leads.

Conclusions: SAECG testing should be considered a standard part of the evaluation of patients with known or suspected ARVD. Further research is needed to confirm the value of SAECG testing in predicting arrhythmia risk and assessing the rate of disease progression, as well as to determine if greater prevalence of SAECG abnormalities in family members of patients with ARVD represents early detection of ARVD. The ongoing multidisciplinary study of right ventricular dysplasia will hopefully answer some of these questions.
Higher Energy Monophasic DC Cardioversion for Persistent Atrial Fibrillation: Is it Time to Start at 360 Joules?
Authors: Boos C , Thomas MD , Jones A , Clarke E , Wilbourne G , More RS
Published: December 2004

Background: Electrical direct‐current cardioversion (DCCV) has become a routine therapy for atrial fibrillation (AF), although some uncertainty remains regarding the optimal energy settings.

Aims: This study examines whether the use of a higher initial energy monophasic shock of 360 joules (J) for external DCCV, in patients with persistent AF would prove more effective, yet as safe, as the use of a lower initial energy 200 J shock.

Methods: A cohort of 107 patients with persistent AF was prospectively randomized to an initial synchronized DCCV shock of 360 J versus 200 J (n = 50 vs 57), followed by a similar shock sequence thereafter of four further shocks of 360 J for the two groups. In all patients the levels of troponin I (cTnI) were measured precardioversion and 18–20 hours later, the following day. In a subgroup of 36 patients in each group, the levels of creatine kinase (CK) and aspartate transaminase (AST) were measured pre‐ and 18–20 hours postcardioversion.

Results: The success rate for DCCV was significantly higher in the 360 J group compared to the 200 J group (96.0% vs 75.4%, P = 0.003). The mean CK IU/L levels (1137.5.0 vs 2411.8, P = 0.014) and AST levels (39.83 vs 52.86, P = 0.010) were significantly lower in the 360 J group compared to the 200 J group. There was no statistical rise in cTnI (μg/L) in either group (P = 1.00). The average number of shocks delivered (1.84 vs 2.56, P = 0.006) was significantly less in the 360 J group than in the 200 J group, although total energy requirements for DCCV were similar for the two groups (662.4 J vs 762.4 J, P = 0.67).

Conclusion: For patients with persistent AF the use of a higher initial‐energy monophasic shock of 360 J achieves a significantly greater success rate, with less skeletal muscle damage (and no cardiac muscle damage) as compared with the traditional starting energy of a 200 J DC shock.
Heart Rate Turbulence following Ventricular Premature Beats in Healthy Controls
Authors: Grimm Wolfram , Sharkova Julia , Christ Michael , Schneider Raphael , Schmidt Georg , Maisch Bernhard
Published: December 2004

Background: Heart rate turbulence (HRT) has recently been described as a strong, independent risk stratifier in postinfarct patients. To date, however, the incidence of false positive HRT findings in adults is unknown. Therefore, we performed a blinded, retrospective analysis of HRT in a prospectively collected database of 110 apparently healthy persons to determine the prevalence and clinical significance of abnormal HRT findings in healthy controls using previously published cut‐off values.

Methods and Results: The study included 43 out of 110 apparently healthy adults, in whom a sufficient number of ventricular premature beats were available for HRT analysis on 24‐hour Holter recordings. The HRT slope was dichotomized at 2.5 ms per R‐R interval and HRT onset was dichotomized at 0% using previously established criteria to define an abnormal HRT analysis in postinfarct patients. Using these definitions, abnormal HRT results were found in 2 out of 43 controls (5%) for HRT slope and in 8 out of 43 controls (19%) for HRT onset without any cardiac deaths during 32 ± 15 months follow‐up.

Conclusions: The incidence of false positive HRT results in healthy middle‐aged volunteers is low for HRT slope (5%), but not for HRT onset (19%) when previously published cut‐off values are used to define abnormal HRT results. Thus, HRT slope dichotomized at 2.5 ms per R‐R interval, but not HRT onset dichotomized at 0%, may be used as a relatively specific tool for risk stratification in middle‐aged persons.