bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Alcohol on Polysomnographically Recorded Sleep in Healthy Subjects
Authors: Feige Bernd , Gann Horst , Brueck Rigo , Hornyak Magdolna , Litsch Simone , Hohagen Fritz , Riemann Dieter
Published: August 2006

Background: After studying the sleep of alcohol‐dependent patients at the beginning and over the course of abstinence in earlier studies, our interest in the current study focused on the direct effect of 2 doses of alcohol [0.03 and 0.1% blood alcohol level (BAL)] on healthy sleep. This is the first polysomnographic study testing the impact of 2 doses of alcohol ingestion (thus reflecting “normal” social drinking and alcohol abuse) in a single‐blind randomized design in healthy volunteers. The study evaluated a short‐term acute drinking period for 3 and 2 days of withdrawal from alcohol not only for polysomnographic variables but also for subjective estimates of sleep quality.

Methods: In a crossover design with a 1‐week interval, healthy subjects received alcohol to raise their blood alcohol to either 0.03 or 0.1% BAL at bedtime for 3 consecutive nights after an alcohol‐free baseline night. Objective (polysomnography) and subjective sleep (questionnaires) was recorded each night. During the following 2 days, alcohol was discontinued with simultaneous measurements of sleep to gauge withdrawal effects.

Results: At a dose of alcohol leading to BAL of 0.03%, no clear effects could be detected. Following an evening BAL of 0.1%, a hypnotic‐like effect (shortened sleep latency, reduced number of wake periods, decreased stage 1 sleep) occurred primarily during the first half of the night with signs of rebound effects being already present during the second half of the night (increased stage 1 sleep). At this dose, alcohol significantly increased slow‐wave sleep (SWS) in the first half of the night and reduced REM density in the beginning of the night. After discontinuation of the higher alcohol dose, REM sleep amount increased. No significant withdrawal or rebound effects could be observed for parameters of sleep continuity during the 2 nights after discontinuation from alcohol at a BAL of 0.1%.

Conclusions: Owing to the small sample size, the results of this study need to be interpreted with caution. Short‐term moderate alcohol consumption (BAL 0.03%) did not significantly alter objective or subjective parameters of sleep. Higher doses of alcohol resulting in a BAL level of 0.10% immediately before going to bed mainly influenced sleep in the first half of the night, resembling the effects of a short‐acting hypnotic drug, including a suppression of phasic aspects of REM sleep (REM density). Interestingly, analysis of the latter part of these nights indicated the immediate presence of withdrawal effects (increased light sleep). No statistically significant effects on sleep parameters were observable during the 2 nights of withdrawal from alcohol at the higher BAL. Interpreted carefully, our data indicate that negative effects on sleep occur already with short‐term use of alcohol at doses of BAL of 0.10%, despite hypnotic‐like effects during the first hours of sleep, especially during the latter part of the night.
Cognitive Performance in Long‐Term Abstinent Alcoholic Individuals
Authors: Fein George , Torres Jennifer , Price Leonard J. , Di Sclafani Victoria
Published: August 2006

Background: There are few investigations of the potential recovery of neurocognitive function in chronic alcoholic samples after very‐long‐term abstinence. The current study examined cognitive abilities in middle‐aged (mean age 46.8 years), long‐term abstinent alcoholic individuals (LTAA). Twenty‐five LTAA men and 23 LTAA women abstinent for an average of 6.7 years were compared with an equal number of gender and age‐comparable normal controls (NC). We examined the association of neurocognitive variables with age, duration of abstinence, alcohol use measures, and the density of a family history of problem drinking.

Methods: Long‐term abstinent alcoholic individuals and NC underwent comprehensive neuropsychological assessment. Performance was measured in the following 9 domains: abstraction/cognitive flexibility, attention, auditory working memory, immediate memory, delayed memory, psychomotor function, reaction time, spatial processing, and verbal skills.

Results: Long‐term abstinent alcoholic individuals performed similarly to NC, except for deficits in the spatial processing domain. The spatial processing results must be interpreted with caution because of multiple comparison issues; however, spatial processing deficits are among the impairments most often reported in abstinent alcoholic individuals. None of the cognitive measures were associated with length of abstinence, any alcohol use variable, or family history measure.

Conclusions: Very‐long‐term abstinence resolves most neurocognitive deficits associated with alcoholism, except for the suggestion of lingering deficits in spatial processing.
A Theoretical Argument for Inherited Thiamine Insensitivity as One Possible Biological Cause of Familial Alcoholism
Authors: Manzardo Ann M. , Penick Elizabeth C.
Published: August 2006

Thiamine deficiency has been specifically linked to the development of Wernicke–Korsakoff syndrome (WK)—a degenerative brain disorder that is typically associated with alcoholic drinking. Alcoholism‐related thiamine deficiency is a major cause of WK. However, an inherited abnormality in thiamine utilization has been identified in some WK patients that may predispose heavy drinkers to this severe neurological syndrome. Individuals who possess this variant require more thiamine throughout their lives to prevent them from experiencing thiamine deficiency. Recent prospective studies have implicated early childhood nutritional and environmental influences in the etiology of alcoholism in adults. These studies have suggested that developmental abnormalities involving brain white matter growth might precipitate the later development of alcoholism possibly by altering the emerging reward‐related brain systems. Brain white matter growth is highly sensitive to nutritional deficiency (including thiamine deficiency) and oxidative injury, especially during the perinatal period.

The proposed model of familial alcoholism hypothesizes that an inherited insensitivity to thiamine can precipitate brain abnormalities very early in life that will greatly increase the risk of developing alcoholism in adulthood.

This paper offers a heuristic model of a possible mechanism by which both inherited and environmental factors related to thiamine utilization might coaggregate to cause alcoholism.
Neurobehavioral Characteristics of Children with Fetal Alcohol Spectrum Disorders in Communities from Italy: Preliminary Results
Authors: Kodituwakku Piyadasa , Coriale Giovanna , Fiorentino Daniela , Aragón Alfredo S. , Kalberg Wendy O. , Buckley David , Gossage J. Phillip , Ceccanti Mauro , May Philip A.
Published: August 2006

Background: There has been considerable effort expended on defining neurobehavioral characteristics of children with fetal alcohol spectrum disorders (FASD). Children with FASD display a range of cognitive deficits and behavioral problems. In this article, we report on the neurobehavioral characteristics of children with FASD in selected communities in Italy. It was expected that both inattentive and hyperactive/impulsive characteristics would discriminate children with FASD from controls and that the groups would also differ on intellectual functioning, language comprehension, and academic skills.

Methods: Eighty‐two children, 22 diagnosed with FASD and 60 control children, participated in this study. The children were administered tests of nonverbal reasoning, language comprehension, academic achievement, and behavior.

Results: On tests of nonverbal reasoning and language comprehension, the FASD group earned lower scores than did controls. Moreover, on a test of academic achievement the FASD group scored lower. When comparing these 2 groups on disruptive behavioral symptomatology, similar results were obtained, the FASD group showing greater attentional difficulties and hyperactivity/impulsivity behaviors and more overall behavioral problems. Stepwise logistic regression analysis showed that a model containing inattention and error scores on the language comprehension task correctly classified 85% of the participants. Compared with the control group, a significantly greater proportion of children with FASD met the Diagnostic and Statistical Manual of Mental Disorders—fourth edition (DSM‐IV) criteria of ADD, inattentive type, as reported by teachers. In contrast, hyperactive symptoms among children with FASD were comparable with the control group. Teachers rated children with FASD as having more inattentive behaviors and as performing lower in academic skills than controls. The association between reported hyperactivity symptoms and achievement scores was nonsignificant for both language and math scores, suggesting that it is not the hyperactivity causing problems, but the child's inattention.

Conclusions: This research indicates that a nonclinic‐referred sample of Italian children with FASD display a profile of neurobehavioral functioning consistent with that reported by other researchers. Furthermore, the neurobehavioral characteristic most identified with children diagnosed with FASD was inattention followed by hyperactivity.
Maximum Quantity Consumed and Alcohol‐Related Problems: Assessing the Most Alcohol Drunk With Two Measures
Authors: Greenfield Thomas K. , Nayak Madhabika B. , Bond Jason , Ye Yu , Midanik Lorraine T.
Published: August 2006

Purposes: The maximum amount of alcohol consumed on any day is an important indicator of problem drinking. This study examined the ability of 2 maximum measures, taken individually and in combination, to predict alcohol‐related consequences and dependence symptoms.

Method: We analyzed data from 4,296 current drinkers who participated in the 2000 National Alcohol Survey (N10) and provided complete data on several alcohol measures. Items included the most they drank in any day in the past 12 months assessed by 2 questions: a standard question with a 6‐level categorical response format and an open‐ended (continuous) question referencing the occasion that you had the most to drink that followed items on drinking contexts.

Results: In a within‐subjects analysis, more than two‐thirds of the respondents provided consistent responses on both questions (69.9%), 12.4% respondents reported higher maximum quantities on the open‐ended question partitioned into equivalent categories, and 17.7% reported a higher maximum on the initial categorical question. In multiple logistic regression analyses predicting alcohol‐related consequences, the continuous open‐ended maximum or the mean of the 2 maximum items were the strongest predictors, whereas for predicting alcohol dependence symptoms, the maximum of the open‐ended and closed‐ended maximum items was a better predictor than each measure alone.

Conclusion: Although categorical response formats generally capture high‐quantity drinking better than open‐ended formats, use of a second, alternatively formatted “most drunk” question may modestly improve ability to predict survey indicators of alcohol use disorders.
Estimates of the Mean Alcohol Concentration of the Spirits, Wine, and Beer Sold in the United States and Per Capita Consumption: 1950 to 2002
Authors: Kerr William C. , Greenfield Thomas K. , Tujague Jennifer
Published: August 2006

Background: Estimates of per capita consumption of alcohol in the United States require estimates of the mean alcohol content by volume (%ABV) of the beer, wine, and spirits sold to convert beverage volume to gallons of pure alcohol.

Methods: The mean %ABV of spirits is estimated for each year from 1950 to 2002 and for each state using the %ABV of major brands and sales of sprits types. The mean %ABV of beer and wine is extrapolated to cover this period based on previous estimates. These mean %ABVs are then applied to alcohol sales figures to calculate new yearly estimates of per capita consumption of beer, wine, spirits, and total alcohol for the United States population aged 15 and older.

Results: The mean %ABV for spirits is found to be lower than previous estimates and to vary considerably over time and across states. Resultant per capita consumption estimates indicate that more alcohol was consumed from beer and less from wine and spirits than found in previous estimates.

Conclusions: Empirically based calculation of mean %ABV for beer, wine, and spirits sold in the United States results in different and presumably more accurate per capita consumption estimates than heretofore available. Utilization of the new estimates in aggregate time‐series and cross‐sectional models of alcohol consumption and related outcomes may improve the accuracy and precision of such models.
Heart Rate Variability and Sympathetic Skin Response in Male Patients Suffering From Acute Alcohol Withdrawal Syndrome
Authors: Bär Karl‐Jürgen , Boettger Michael Karl , Neubauer Rene , Grotelüschen Marei , Jochum Thomas , Baier Vico , Sauer Heinrich , Voss Andreas
Published: August 2006

Background: Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods.

Methods: We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients suffering from mild AW syndrome (n=20, no treatment required) and in patients with moderate to severe AW syndrome (n=20, clomethiazole treatment) in the acute stage. Sympathovagal influence was quantified using measures of time and frequency domain of HRV as well as modern nonlinear parameters (compression entropy). Furthermore, we obtained latencies and amplitudes of SSR to quantify isolated sympathetic influence. Measures were obtained during the climax of withdrawal symptomatology before treatment, 1 day after climax, and shortly before discharge from hospital. Alcohol withdrawal scores were obtained and correlated to autonomic measures.

Results: Ambulatory blood pressure and AW scores revealed characteristic withdrawal symptoms in both patient groups. Apart from the nonlinear parameter compression entropy, Hc, measures of HRV revealed no sign of autonomic dysfunction in contrast to the significantly increased heart rates at the time of admission. Latencies and amplitudes of SSR did not indicate any increase of sympathetic activity. A negative correlation was found between Hc and mental withdrawal symptoms.

Conclusions: We show here that classical measures for autonomic nervous system activity such as HRV and SSR are not suitable for describing the autonomic changes seen in acute AW, although a major role for the sympathetic nervous system has been proposed. This might be due to multiple dysregulation of metabolites in AWS or to subtle alcohol‐induced damage to neuronal structures, issues that should be addressed in future studies.
Smoke Exposure and Ethanol Ingestion Modulate Intrapulmonary Polymorphonuclear Leukocyte Killing, but Not Recruitment or Phagocytosis
Authors: Vander Top Elizabeth A. , Perry Greg A. , Snitily Mary U. , Gentry‐Nielsen Martha J.
Published: August 2006

Background: People who smoke and abuse alcohol are uniquely susceptible to pulmonary infections caused by Streptococcus pneumoniae, the pneumococcus. The primary cellular defense against pneumococci within the lungs is the polymorphonuclear leukocyte (PMN). Cigarette smoke and ethanol (EtOH) are known to alter certain PMN functions, but little is known about their concurrent effects.

Methods: Male Sprague–Dawley rats were exposed twice daily for 8 weeks to cigarette smoke (smoke‐exposed) or room air (sham‐exposed). During the final week of exposure, the rats were pair‐fed a liquid diet containing either 36 or 0% EtOH calories. Polymorphonuclear leukocytes were prerecruited into the rats' lungs by transtracheal injection of lipopolysaccharide. Five hours later, the rats were infected transtracheally with S. pneumoniae, and PMN recruitment, phagocytosis, and bactericidal activity were quantified within their lungs. Chemokine levels were also measured in bronchoalveolar lavage fluids, lung homogenates, and sera.

Results: Neither PMN recruitment nor phagocytic uptake of pneumococci was altered by EtOH ingestion or smoke exposure. Killing of the organisms, however, was significantly decreased in sham‐exposed, but not smoke‐exposed, rats ingesting EtOH. Parallel results were determined for serum cytokine‐induced neutrophil chemoattractant‐1 (CINC‐1), with EtOH ingestion significantly decreasing the levels in sham‐exposed, but not smoke‐exposed, rats. Pulmonary levels of macrophage inflammatory protein‐2 (MIP‐2) and CINC‐1 were highly elevated by the combination of EtOH and smoke.

Conclusions: One week of EtOH ingestion by rats impaired the ability of their PMNs to kill S. pneumoniae within their lungs. This was not due to decreased recruitment of the PMNs to the lungs or to diminished phagocytosis of intrapulmonary pneumococci. The addition of twice‐daily cigarette smoke exposure to this short‐term EtOH ingestion model restored PMN bactericidal ability to levels observed in the absence of either treatment. These EtOH‐induced and smoke‐induced alterations in PMN killing may be related to alterations in both pulmonary and systemic inflammatory chemokine levels.
Inhibition of PAR4 Signaling Mediates Ethanol‐Induced Attenuation of Platelet Function In Vitro
Authors: Kasuda Shogo , Sakurai Yoshihiko , Shima Midori , Morimura Yoshifumi , Kudo Risa , Takeda Tomohiro , Ishitani Akiko , Yoshioka Akira , Hatake Katsuhiko
Published: August 2006

Background:Reduction in coronary heart disease morbidity in response to moderate consumption of alcoholic beverages may be partly mediated by ethanol‐induced inhibition of platelet function. However, the precise mechanisms by which ethanol modulates platelet activation induced by thrombin, which plays a central role in hemostasis, remain unclear. The goal of this study was to investigate ethanol‐induced changes in platelet function and clarify the underlying mechanisms including PAR1 and PAR4 activity and [Ca2+]idynamics in vitro.

Methods:Platelet aggregation, increase in intracellular calcium ([Ca2+]i), and release of platelet factor 4 andβ‐thromboglobulin induced byα‐thrombin, PAR1‐agonist peptide (AP), or PAR4‐AP were assessed in the presence or absence of ethanol.

Results:Ethanol exposure inhibited low‐dose thrombin (0.5 nM)‐induced aggregation but not an increase in [Ca2+]i. In contrast, ethanol had no effect on high‐dose thrombin (10 nM)‐induced aggregation or the [Ca2+]iincrease. Ethanol did not significantly inhibit thrombin‐induced release of platelet factor 4 andβ‐thromboglobulin. Ethanol reduced PAR1‐AP‐induced aggregation, but did not affect the spike form of [Ca2+]iincrease. In contrast, ethanol inhibited the increase in [Ca2+]ias well as the aggregation in response to PAR4‐AP and resulted in delayed [Ca2+]ipeak time. Furthermore, ethanol inhibited both PAR1‐AP‐ and PAR4‐AP‐induced platelet factor 4 andβ‐thromboglobulin release.

Conclusions:These data suggest that ethanol inhibits platelet aggregation via inhibition of PAR4 signaling and subsequent inhibition of Ca2+influx and granule release. This phenomenon may contribute to the reduction in coronary heart disease morbidity in response to consumption of alcoholic beverages.
Chronic Ethanol Consumption Inhibits Hepatic Natural Killer Cell Activity and Accelerates Murine Cytomegalovirus‐Induced Hepatitis
Authors: Pan Hong‐na , Sun Rui , Jaruga Barbara , Hong Feng , Kim Won‐Ho , Gao Bin
Published: August 2006

Background: Chronic alcohol drinking accelerates the progression of liver disease in patients with hepatitis viral infection; however, the underlying mechanisms are not fully understood.

Methods: Here, we examined the effects of chronic ethanol feeding on hepatic natural killer (NK) cells and liver injury in 2 murine models of liver injury: injection of synthetic double‐stranded RNA polyinosinic‐polycytidylic acid (poly I:C), which mimics viral infection, and infection with murine cytomegalovirus (MCMV). Mice were fed the Lieber‐DeCarli liquid diet containing 5% (vol/vol) ethanol for 8 weeks, resulting in a significant decrease in the percentage and total number of NK cells in the liver.

Results: In control, pair‐fed mice, poly I:C injection induced NK cell accumulation in the liver and activated hepatic NK cell cytotoxicity, whereas such induction and activation were diminished in ethanol‐fed mice. Treatment with poly I:C also induced expression of NKG2D, granzyme B, perforin, Fas L, TRAIL, and IFN‐γ on liver lymphocytes, which were delayed or reduced in ethanol‐treated mice compared with pair‐fed mice. In contrast, chronic ethanol feeding did not affect poly I:C–induced mild liver injury. Furthermore, MCMV infection activated hepatic NK cells and induced hepatic inflammation and injury. Chronic ethanol consumption inhibited hepatic NK cell activation during MCMV infection, but enhanced MCMV‐induced liver injury, viral titer, and inflammation in the liver.

Conclusions: Taken together, these findings suggest that chronic ethanol consumption decreases hepatic NK activity, thereby accelerating MCMV‐induced hepatitis and liver injury.
Acute and Chronic Alcohol Abuse Modulate Immunity
Authors: Brown Lou Ann S. , Cook Robert T. , Jerrells Thomas R. , Kolls Jay K. , Nagy Laura E. , Szabo Gyongyi , Wands Jack R. , Kovacs Elizabeth J.
Published: August 2006

This article represents the proceedings of the Alcohol and Immunology Research Interest Group (AIRIG) meeting, a satellite workshop held at the 37th Annual Meeting of the Society for Leukocyte Biology. The meeting was sponsored by the AIRIG and the National Institute on Alcohol Abuse and Alcoholism. The presentations were as follows: (1) Effects of Ethanol on Immune Response to Hepatitis C Virus by Jack R. Wands, (2) Alcohol and Alveolar Macrophage Dysfunction: The Role of Chronic Oxidant Stress by Lou Ann S. Brown, (3) T Cell Responses to Listeria monocytogenes in Mice on a Chronic Ethanol Exposure Protocol by Robert T. Cook, (4) Mechanisms of Acute and Chronic Alcohol Consumption on Severity of Viral Infections by the Liver and Pancreas by Thomas R. Jerrells, (5) Acute and Chronic Effects on Macrophage Ectodomain Shedding: Implications for Lung Host Defenses by Jay K. Kolls, (6) Increased Susceptibility to Pseudomonas Infection of Burn‐Injured Mice Given Alcohol Before Injury by Elizabeth J. Kovacs, (7) Regulation of Tumor Necrosis Factor α Expression in Macrophages by Chronic Ethanol by Laura E. Nagy, and (8) Hepatitis C Virus Infection and Alcohol Use by Gyongyi Szabo. Meeting coorganizers were Elizabeth J. Kovacs, Lou Ann S. Brown, Thomas R. Jerrells, and Robert T. Cook.
Using the Internet and Email for Health Purposes: The Impact of Health Status*
Authors: Goldner Melinda
Published: August 2006

Objective. Increasingly, people use the Internet and email for health purposes; however, we know little about whether this varies by health status. This study examines whether sick or healthy people are more likely to access the Internet, conduct online health searches, and exchange emails regarding health issues.

Methods. We conduct multivariate analysis on a random sample of 2,038 adults.

Results. Despite greater Internet access, respondents in excellent/good health are less likely to say they conduct online health searches because they have no health concerns or are satisfied with other health sources. In contrast, sick and disabled respondents are more likely to seek medical information online, and do so more frequently. They are also more likely to exchange health emails with friends and physicians.

Conclusions. Practitioners especially need to educate their sicker patients about the uneven quality of online health information since they are more likely than healthier patients to conduct online health searches.
Robotic Implantation of a Multichamber Cardiac Resynchronization Therapy Defibrillator
Authors: SHALABY ALAA , SHARMA MAHESH S. , ZENATI MARCO A.
Published: August 2006

Transvenous implantation of a cardiac resynchronization therapy defibrillator (CRT‐D) may not be feasible due to anatomic constraints. One of the most notable advances in minimal‐access heart surgery has been the introduction of robotic telemanipulation systems. We present a challenging case in which a CRT‐D system was implanted using a robotic approach. Feasibility of such an approach expands the horizons for delivery of CRT‐D therapy.
Inappropriate ICD Therapy: Does Device Configuration Make a Difference
Authors: SOUNDARRAJ DWARAKRAJ , THAKUR RANJAN K. , GARDINER JOSEPH C. , KHASNIS ATUL , JONGNARANGSIN KRIT
Published: August 2006

Introduction: Inappropriate implantable cardioverter defibrillator (ICD) therapy (IT) is a common complication in patients with ICD. IT is commonly triggered by supraventricular tachycardias (SVT). Dual chamber ICDs (D‐ICDs) may distinguish SVT from ventricular tachycardia/ventricular fibrillation better than single chamber ICDs (S‐ICDs) and may be associated with a smaller incidence of IT.

Methods: We reviewed the charts of 386 patients who had an ICD implanted for an AHA class I indication. Intracardiac electrograms were used to classify shocks as either appropriate or inappropriate.

Results: Of 295 patients with an S‐ICD, 66 (22.3%) received IT, compared to 5 (5.4%) of 91 patients with a D‐ICD. The likelihood of being event‐free at 1, 2, 3, and 4 years was 96.1%, 96.1%, 96.1%, and 89% for patients with D‐ICD and 80.7%, 72.7%, 69.6%, and 66.4%, respectively, for patients with S‐ICD (P < 0.001). Multivariate analysis showed no significant association with age, sex, history of atrial fibrillation, history of hypertension, or ejection fraction. SVTs were the commonest cause of IT in our patients.

Conclusion: Patients with D‐ICD are less likely to receive IT as compared to patients with S‐ICD.
Seasonal Variations of Ventricular Arrhythmia Clusters in Defibrillator Recipients
Authors: STUBER THOMAS , EIGENMANN CHRISTA , DELACRÉTAZ ETIENNE
Published: August 2006

Background: Clustering ventricular arrhythmias are the consequence of acute ventricular electrical instability and represent a challenge in the management of the growing number of patients with an implantable cardioverter‐defibrillator (ICD). Triggering factors can rarely be identified.

Objectives: Several studies have revealed seasonal variations in the frequency of cardiovascular events and life‐threatening arrhythmias, and we sought to establish whether seasonal factors may exacerbate ventricular electrical instability leading to arrhythmia clusters and electrical storm.

Methods: Two hundred and fourteen consecutive defibrillator recipients were followed‐up during 3.3 ± 2.2 years. Arrhythmia cluster was defined as the occurrence of three or more arrhythmic events triggering appropriate defibrillator therapies within 2 weeks. Time intervals between two clusters were calculated for each month and each season, and were compared using Kruskal‐Wallis test and Wilcoxon‐Mann‐Whitney test with Bonferroni adjustment.

Results: During a follow‐up of 698 patient years, 98 arrhythmia clusters were observed in 51 patients; clustering ventricular arrhythmias were associated with temporal variables; they occurred more frequently in the winter and spring months than during the summer and fall. Accordingly, the time intervals between two clusters were significantly shorter during winter and spring (median and 95% CI): winter 16 (5–19), spring 11.5 (7–25), summer 34.5 (15–55), fall 50.5 (19–65), P = 0.0041.

Conclusion: There are important seasonal variations in the incidence of arrhythmia clusters in ICD recipients. Whether these variations are related to environmental factors, change in physical activity, or psychological factors requires further study.
Evidence for Increased Atrial Sympathetic Innervation in Persistent Human Atrial Fibrillation
Authors: GOULD PAUL A. , YII MICHAEL , MCLEAN CATRIONA , FINCH SAMARA , MARSHALL TANNEALE , LAMBERT GAVIN W. , KAYE DAVID M.
Published: August 2006

Objective: In this study, we aimed to compare the level of atrial sympathetic innervation in human atrial fibrillation (AF) to that in sinus rhythm (SR).

Background: Histological studies of atrial tissue obtained from animals with experimentally induced AF indicate that sympathetic hyperinnervation could play a role in the pathogenesis of AF.

Methods: In 24 patients (12 in SR and 12 in AF) undergoing bypass surgery, we collected right atrial appendage tissue. In AF patients, left atrial appendage tissue was also acquired. The degree of sympathetic innervation was quantified by measuring the amount of staining for tyrosine hydroxylase (TH) and tissue norepinephrine (NE). In conjunction, nerve growth factor (NGF) mRNA expression was assessed by real‐time polymerase chain reaction (PCR). Growth‐associated protein 43 (GAP43) immunostaining was used to assess degree of new neural growth.

Results: When corrected for differences in tissue fibrosis, the expression of both TH (AF 0.45 ± 0.1%, SR 0.09 ± 0.03%, P = 0.02) and tissue NE (AF 358 ± 49 pg/mg, SR 225 ± 39 pg/mg, P = 0.04) was greater in atrial tissue of the AF cohort. The degree of atrial TH staining (P = 0.01) and NE content (P < 0.001) was also significantly greater in the right compared with left atrial samples in the AF cohort. There were no differences in NGF mRNA expression or GAP43 staining.

Conclusion: This study provides evidence for the presence of heightened atrial sympathetic innervation in patients with persistent AF, suggesting autonomic remodeling may be part of atrial substrate for AF.
QRS Duration in High‐Resolution Methods and Standard ECG in Risk Assessment After First and Recurrent Myocardial Infarctions
Authors: KORHONEN PETRI , HUSA TERHI , TIERALA ILKKA , VÄÄNÄNEN HEIKKI , MÄKIJÄRVI MARKKU , KATILA TOIVO , TOIVONEN LAURI
Published: August 2006

Background: Prolonged QRS duration (QRSd) is associated with increased mortality after myocardial infarction (MI). Only little data exist about its predictive ability and relationships to clinical variables in the present era of active treatment of myocardial ischemia and cardiac dysfunction. We investigated whether QRSd in high‐resolution methods and standard ECG predict arrhythmic events and cardiac death in post‐infarction patients with cardiac dysfunction and how it relates to clinical variables, with a special emphasis on history of previous MI.

Methods and Results: Patients (n = 158) with acute MI and cardiac dysfunction had magnetocardiography (MCG), signal‐averaged ECG (SAECG), and ECG registered at discharge. Patients with a previous MI had significantly longer QRSd although their left ventricular function was almost similarly impaired. During the mean follow‐up of 50 ± 15 (range 1–72) months, 32 patients died and 17 (53%) of the deaths were classified as cardiac. Eighteen patients had an arrhythmic event. QRSd >121 ms in MCG and >114 ms in SAECG were significant predictors of arrhythmic events and cardiac death, whereas QRSd in ECG predicted only cardiac death. In multivariate analysis, QRSd in MCG (hazard ratio (HR) = 3.6, P = 0.007) and SAECG (HR = 4.6, P = 0.016) predicted only arrhythmic events, whereas QRSd in ECG was an independent predictor of cardiac death.

Conclusions: Prolonged QRSd in MCG and SAECG are powerful indicators of the arrhythmia substrate in post‐infarction patients with cardiac dysfunction, whereas prolonged QRSd in standard ECG associates with increased risk of cardiac death.
Magnetic Resonance Imaging Abnormalities in Right Ventricular Outflow Tract Tachycardia and the Prediction of Radiofrequency Ablation Outcome
Authors: KRITTAYAPHONG RUNGROJ , SAIVIROONPORN PAIRASH , BOONYASIRINANT THANANYA , NAKYEN SUPAPORN , THANAPIBOONPOL PRAJAK , WATANAPRAKARNCHAI WIPAWIN , RUKSAKUL KRONGKARN , KANGKAGATE CHARUWAN
Published: August 2006

Background: Recent reports have shown abnormalities on cardiac magnetic resonance imaging (MRI) in patients with right ventricular outflow tract (RVOT) tachycardia.

Objectives: Objectives of this study were to demonstrate abnormalities on MRI and signal‐averaged ECG (SAECG) in patients with RVOT tachycardia and their correlation with the outcome of radiofrequency (RF) ablation.

Methods: We studied 41 patients with symptomatic RVOT tachycardia and 15 controls. SAECG and cardiac MRI were performed on every subject. An evaluation of structural abnormality, chamber size, function, and wall motion abnormality of the left and right ventricle was performed by MRI. Focal wall thinning was evaluated by the black blood technique and fatty infiltration was evaluated by the T1 image with and without fat suppression.

Results: MRI abnormalities were demonstrated in 24 (58.5%) patients with RVOT tachycardia. The abnormalities included localized wall bulging in 22 (53.7%), focal wall thinning in 10 (24.4%), and fatty replacement in 9 (22%) patients. MRI abnormality was found in only one patient in the control group (P < 0.001). Late potentials from SAECG were demonstrated in six (10.7%) patients but none in the controls (P = 0.117). Among 29 patients who underwent RF ablation, 3 patients had a failed procedure and 3 having arrhythmia recurrence needed repeated ablation. MRI abnormalities and late potentials were associated with an unfavorable outcome of RF ablation.

Conclusions: MRI abnormalities were frequently found in patients with RVOT tachycardia. MRI abnormalities and late potentials can predict outcomes of RF ablation.
Predictors of Response to the Head‐Up Tilt Test in Patients with Unexplained Syncope or Presyncope
Authors: KAZEMI BABAK , HAGHJOO MAJID , ARYA ARASH , SADR‐AMELI MOHAMMAD ALI
Published: August 2006

Background: Unexplained syncope is a relatively frequent symptom, mostly caused by a neurocardiogenic reaction. The purpose of this study was to determine predictors of response to head‐up tilt testing (HUTT) in patients with unexplained syncope or presyncope.

Methods: HUTT was done in 640 consecutive patients with unexplained syncope or presyncope (393 men, mean age 45±19 years) after initial workup including history, physical examination, and appropriate laboratory evaluation.

Results: Three hundred and forty‐four (54%) patients had a positive result. The most common type of response was mixed type (46%) followed by vasodepressor (39%) and cardioinhibitory (15%) types. Age, gender, presence of structural heart disease, baseline heart rhythm, and the presenting symptom before the test failed to predict a positive response to HUTT, but among patients with a positive response to the test, age (OR: 1.54, CI = 1.04–2.47, P = 0.016) and presyncope (OR: 2.16, CI = 1.2–3.85, P = 0.008) as the presenting symptom predicted a vasodepressor type of response. The age (OR: 1.58, CI = 1.29–3.94, P = 0.01) and presyncope (OR: 4.6, CI = 1.74–12.24, P = 0.001) were also predictors for test positivity in the active stage.

Conclusions: There is an age‐related gradient in hemodynamic response during neurocardiogenic syncope. The elderly patients more commonly had a vasodepressor and late response, in the active stage, but young subjects more commonly experienced an earlier and cardioinhibitory or mixed responses in the passive stage.
Ultrasound‐Guided Venous Access for Permanent Pacemaker Leads
Authors: JONES DAVID G. , STILES MARTIN K. , STEWART JAMES T. , ARMSTRONG GUY P.
Published: August 2006

Background: Existing methods of venous access for permanent pacemaker leads have disadvantages. We documented learning times for ultrasound‐guided lead implantation and compared them with cephalic venotomy technique.

Methods: Two implanters learnt ultrasound‐guided technique by implanting consecutive pacemaker patients. When procedural times stabilized, we reverted to our normal cephalic approach. We measured lead placement time and screening time from skin incision until all leads were placed in superior vena cava were measured.

Results: Initial strategy adopted was ultrasound for 60, then cephalic for 38 patients. There were no significant differences between groups in baseline characteristics or number of leads implanted. Lead placement and screening times were significantly shorter for ultrasound, despite inclusion of all learning cases. There was a high success rate for both strategies (88% ultrasound, 87% cephalic). There was significantly greater use of pressure dressings with ultrasound, but no difference in pocket hematoma or pneumothorax. There was a trend for more predictable lead implant times with ultrasound and fluoroscopy times were shorter and more predictable. Independent predictors of lead placement time were body mass index, operator, initial strategy (ultrasound vs cephalic), and procedure number.

Conclusion: Ultrasound‐guided venepuncture for placement of permanent pacing leads is quick to learn and achieves faster lead placement times with shorter and more predictable fluoroscopy time when compared with the cephalic venotomy technique.
Multi‐Center Clinical Experience with a Lumenless, Catheter‐Delivered, Bipolar, Permanent Pacemaker Lead: Implant Safety and Electrical Performance
Authors: GAMMAGE MICHAEL D. , LIEBERMAN RANDY A. , YEE RAYMOND , MANOLIS ANTONIS S. , COMPTON STEVEN J. , KHAZEN CÉSAR , SCHAAF KATIE , OLESON KIMBERLY A. , CROSSLEY GEORGE H. ,   for the Worldwide SelectSecure Clinical Investigators
Published: August 2006

Purpose: Reduced lead diameter and reliability can be designed into transvenous permanent pacing leads through use of redundant insulation and removal of the stylet lumen. The model 3830 lead (Medtronic Inc., Minneapolis, MN, USA) is a bipolar, fixed‐screw, steroid‐eluting, lumenless, 4.1‐Fr pacing lead. Implantation can be performed in a variety of right heart sites using a deflectable catheter (Model 10600, Medtronic). Lead performance and safety were studied.

Methods: Two prospective trials of 338 implanted subjects from 56 global sites were conducted. Electrical and safety data were obtained at implant, pre‐discharge, and up to 18 months post‐implant. Leads were implanted at traditional and alternate right heart sites.

Results: The study enrolled 338 subjects (204 males, 70.6 ± 11.6 years) followed‐up for a mean of 10.2 months (range, 0–21.6). Mean P‐wave amplitudes ranged from 3.2 mV at 3 months to 2.9 mV at 18 months, while mean atrial pulse width thresholds at 2.5 V ranged from 0.07 ms at 3 months to 0.09 ms at 18 months. Mean R‐wave amplitudes ranged from 11.3 mV to 11.1 mV and mean ventricular pulse width thresholds at 2.5 V ranged from 0.10 ms to 0.14 ms. There were 22 ventricular and 12 atrial lead complications within 3 months post‐implant. Survival from lead‐related complications improved to a clinically acceptable rate in the cohort of patients when revised implant techniques were employed.

Conclusions: With the use of recommended implant techniques, the study results support the electrical efficacy and safety of a catheter‐delivered, lumenless lead in traditional or alternate right atrium or right ventricle sites through 18 months post‐implant.
Role of Rate Control and Regularization Through Pacing in Patients With Chronic Atrial Fibrillation and Preserved Ventricular Function: The VRR Study
Authors: CIARAMITARO GIANFRANCO , SGARITO GIUSEPPE , SOLIMENE FRANCESCO , MAGLIA GIANPIERO , VICENTINI ALFREDO , DI DONATO GIOVANNI , RACITI GIOVANNI , PARRINELLO GIOVANNI , DEL GIUDICE GIOVANNI BATTISTA
Published: August 2006

Aim: High heart rates in chronic atrial fibrillation (CAF) is one of the factors responsible for hemodynamic alterations and may lead to tachycardiomyopathies. The ventricular rate regulation (VRR) study evaluates the effect of ventricular rate regularization in CAF patients with preserved ventricular function, marked ventricular rate variability, and indications for pacemaker (PM) implantation owing to symptomatic pauses. Rate regularization was achieved using VRR algorithm (INSIGNIA® pacemakers, Guidant Corp., St. Paul, MN, USA).

Methods: One month after PM implantation, 58 patients followed two 3‐month crossover periods (VRR‐OFF; VRR‐ON) in which the VRR algorithm was randomized and compared to fixed rate stimulation at 60 ppm. During follow‐up visits a 6‐minute walk test was performed under partially inhibited conditions (PM at 40 ppm) and ventricular response was recorded. The following parameters were measured: mean ventricular rate (MR), rate variability (RR30), rate recovery after exercise (SLOPE = (R‐END – R‐REC)/(R‐END – 40)), R‐END being the rate at end of walk and R‐REC the rate 1 minute after exercise.

Results: The VRR algorithm decreased rate variability (RR30: −7.36 ± 8.8; P < 0.01) without increasing ventricular rate (MR: −1.11 ± 8.3 P = NS), while SLOPE improved significantly (SLOPE: +15.41 ± 16.8 P < 0.01).

Conclusions: VRR effectively stabilizes rate, without increasing pacing rate above spontaneous rhythm and helps achieve a more favorable autonomic balance, improving rate recovery after exercise.
Percutaneous Lead Implantation Connected to an External Device in Stimulation‐Dependent Patients with Systemic Infection—A Prospective and Controlled Study
Authors: BRAUN MARTIN U. , RAUWOLF THOMAS , BOCK MANIA , KAPPERT UTZ , BOSCHERI ALESSANDRA , SCHNABEL ANDREAS , STRASSER RUTH H.
Published: August 2006

Background: Permanent pacemaker implantation usually is contraindicated in patients with systemic infection. The aim of the present study was to compare two different techniques of transvenous temporary pacing to bridge the infectious situation until permanent pacemaker implantation under infection‐free conditions is possible.

Methods and Results: Forty‐nine patients with systemic infection and hemodynamic‐relevant bradyarrhythmia/asystole were temporarily paced using either a conventional pacing wire/catheter (n = 26, reference group) or a permanent bipolar active pacing lead, which was placed transcutaneously in the right ventricle and connected to an external pacing generator (n = 23, external lead group). In both groups, there were no significant differences in patient characteristics. Whereas the sensing values were almost identical, the median pacing threshold was significantly higher in the reference group (1.0 V vs 0.6 V, P < 0.05). Within comparable duration of pacing (median: 8.2 vs 7.7 days), there were 24 pacing‐related adverse events (including dislocation, resuscitation due to severe bradycardia, or local infection) in the reference group as compared to one event in the external lead group (P < 0.01). None of these complications resulted in cardiac death.

Conclusion: Thus, transvenous pacing with active fixation is safe and associated with a significantly lower rate of pacing‐related adverse events as compared to the standard technique of transvenous pacing using a passive external pacing catheter.
Improvement of Congestive Heart Failure by Upgrading of Conventional to Resynchronization Pacemakers
Authors: MARAI IBRAHIM , GUREVITZ OSNAT , CARASSO SHEMY , NOF EYAL , BAR‐LEV DAVID , LURIA DAVID , ARBEL YARON , FREIMARK DOV , FEINBERG MICHA S. , ELDAR MICHAEL , GLIKSON MICHAEL
Published: August 2006

Aims: To compare the clinical response of patients with right ventricular apical pacing (RVAP) upgraded to cardiac resynchronization therapy (CRT) to that of previously nonpaced heart failure (HF) patients who had de novo CRT implantation.

Background: The role of CRT in patients with wide QRS and HF due to RVAP is less well established than in other CRT candidates.

Methods: Ninety‐eight consecutive patients with CRT were studied (mean age 70, mean ejection fraction 0.23). Group A: patients having RVAP prior to CRT implantation (n = 25), group B: patients without prior RVAP (n = 73). Clinical and echocardiographic parameters were recorded prior to, and 3 months after, CRT implantation.

Results: Group A patients had a wider QRS at baseline compared to group B (203 ± 32 ms vs 163 ± 30 ms respectively, P < 0.001), and a shorter 6‐minute walking distance (222 ± 118 m vs 362 ± 119 m, respectively, P < 0.005). Otherwise, clinical and echocardiographic parameters were not different. At follow up, group A patients had an average 0.7 ± 0.5 decrease in their NYHA functional class, compared to 0.3 ± 0.7 in group B patients (P < 0.05). Six‐minute walking distance increased by 93 ± 113 m in group A, versus 36 ± 120 m in group B (P = 0.22). There was no difference in echocardiographic response to CRT between the groups.

Conclusions: HF patients with prior RVAP demonstrate clinical improvement after upgrading to CRT that is comparable, and in some aspects, even better than that observed in HF patients with native conduction delay who undergo de novo CRT implantation.
Present Understanding of Shock Polarity for Internal Defibrillation: The Obvious and Non‐Obvious Clinical Implications
Authors: KROLL MARK W. , EFIMOV IGOR R. , TCHOU PATRICK J.
Published: August 2006

Background: Uncertainty about the best electrode configuration has combined with the programming flexibility in modern implantable cardioverter‐defibrillators (ICDs) to result in routine polarity reversal during an implant to deal with a high defibrillation threshold (DFT). We feel that this practice is not always supported by the clinical data and the present scientific understanding of defibrillation.

Method: A meta‐analysis of the clinical studies on ICD shock polarity was performed. Subgroup analyses were also performed to test the impact of high DFTs, various tilts, and the use of the hot can electrode. A review of the basic research surrounding the effects of polarity in defibrillation is also presented.

Results: A total of 224 patients were studied. The use of an anodal right ventricular (RV) coil lowers the mean DFT by 14.8% (P = 0.00001). It provides thresholds equal to or lower than cathodal defibrillation in 83% of patients. The fraction of patients with lower anodal DFTs was 94/224 versus 38/224 for cathodal polarity. This phenomenon may be explained by virtual electrode effects. In particular, anodal electrodes tend to produce collapsing wavefronts while cathodal electrodes tend to produce expanding proarrhythmic wavefronts.

Conclusion: In an ICD implant, the RV coil should be the anode. Furthermore, DFT testing beginning with cathodal defibrillation is most likely unnecessary and needlessly extends the procedure's duration and increases the risks for the patient.
The Role of Heart Rate Variability in Prognosis for Different Modes of Death in Chronic Heart Failure
Authors: SANDERCOCK GAVIN RICHARD H. , BRODIE DAVID A.
Published: August 2006

Classic risk factors for mortality due to chronic heart failure (CHF), such as low left ventricular ejection fraction, NYHA functional stage, and increased heart rate perform well in the prediction of death from pump failure. The prediction of sudden cardiac death (SCD) remains somewhat problematic. Numerous studies have analyzed the potential contribution heart rate variability (HRV) can make to risk assessment in CHF. The aim of this review was to summarize the literature and identify the role HRV might play in identifying mode of death, as well as overall mortality risk. In studies where all‐cause mortality or cardiac events were the clinical end point(s), global and slow oscillatory measures of HRV were the strongest risk predictors. In the fewer studies that used SCD as an end point, the strongest risk factors were HRV measures of short‐term oscillations and sympathovagal interaction. We concluded from these findings that different HRV measurements predict different modes of death in CHF.
Additionally, further studies using short‐term analysis of HRV and non‐linear analyses are warranted. Furthermore, studies with multiple end points, which clearly delineate pump failure from SCD, may be useful to identify more clearly the role HRV measures can play in the prediction of SCD.