bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge
Authors: Scheerens H. , Arron J. R. , Zheng Y. , Putnam W. S. , Erickson R. W. , Choy D. F. , Harris J. M. , Lee J. , Jarjour N. N. , Matthews J. G.
Published: October 2013

Background

Interleukin 13 (IL13) is a T‐helper type 2 (Th2) cytokine associated with inflammation and pathology in allergic diseases such as bronchial asthma. We have shown that treatment with lebrikizumab, an anti‐IL13 monoclonal antibody, significantly improves prebronchodilator forced expiratory volume in 1 s (FEV1) in a subset of subjects with uncontrolled asthma.

Objective

To evaluate efficacy and safety of lebrikizumab in subjects with mild asthma who underwent bronchial allergen challenge.

Methods

Twenty‐nine subjects were randomized 1 : 1–5 mg/kg lebrikizumab (n = 13) or placebo (n = 16) administered subcutaneously every 4 weeks over 12 weeks, a total of four doses. Primary efficacy outcome was late asthmatic response (LAR) at Week 13, defined as area under the curve of FEV1 measured 2–8 h following inhaled allergen challenge. Serum biomarkers were measured to verify IL13 pathway inhibition and identify patients with an increased response to lebrikizumab.

Results

At Week 13, the LAR in lebrikizumab subjects was reduced by 48% compared with placebo subjects, although this was not statistically significant (95% confidence interval, −19%, 90%). Exploratory analysis indicated that lebrikizumab‐treated subjects with elevated baseline levels of peripheral blood eosinophils, serum IgE, or periostin exhibited a greater reduction in LAR compared with subjects with lower baseline levels of these biomarkers. Lebrikizumab exerted systemic effects on markers of Th2 inflammation, reducing serum immunoglobulin E (IgE), chemokine ligands 13 and 17 by approximately 25% (P < 0.01). Lebrikizumab was well tolerated.

Conclusion and Clinical Relevance

Lebrikizumab reduced the LAR in subjects with mild asthma. Clinical trial number NCT00781443.
The validity of the body adiposity index in predicting percentage body fat and cardiovascular risk factors among Chinese
Authors: Zhang Zhe‐Qing , Liu Yan‐Hua , Xu Ying , Dai Xiao‐Wei , Ling Wen‐hua , Su Yi‐Xiang , Chen Yu‐Ming
Published: October 2013

Objective

Recent research has suggested that body adiposity index (BAI) correlates more closely with percentage body fat (PBF) than body mass index (BMI). Here, we aimed to evaluate BAI's predictive power for PBF and for obesity‐associated risk factors in the Chinese population.

Subjects

A total of 1707 women and 680 men aged 51–77 years were analysed in this community‐based cross‐sectional study.

Measurements

Body weight, height, waist circumference (WC) and hip circumference (HC) were measured, and BMI and BAI were calculated. Percentage body fat was determined by dual‐energy X‐ray absorptiometry (DXA). Blood pressure, fasting lipid profiles, glucose and Carotid ultrasound examination determined intima‐media thickness (IMT) at the common carotid arteries (CCA) were also measured.

Results

The Pearson correlation analysis indicated a stronger correlation between BAI and PBF when women and men were pooled together, but this effect disappeared in sex‐stratified analysis. Bland–Altman plots suggested that BAI underestimated 5·8% of PBF in women and slightly overestimated 0·28% of PBF in men, but the magnitudes of these biases showed a fat mass‐dependent manner. Both the logistic regression and the receiver operating characteristic curve (ROC) analysis indicated that BAI has an inferior predictive power for the presence of hypertension, dyslipidaemia, metabolic syndrome and CCA‐intima‐media thickening, compared with BMI and WC.

Conclusion

We concluded that BAI was neither a better predictor for PBF nor for cardiovascular risks in Chinese population compared with BMI and WC.
Planning with Multistep Forward Search with Forced Goal‐Ordering Constraints
Authors: Luo Jiangfeng , Zhu Cheng , Zhang Weiming , Liu Zhong
Published: October 2013

To solve a real‐world planning problem with interfering subgoals, it is essential to perform early detection of subgoal dependencies and achieve the subgoals in the correct order. This is also the case for planning problems with forced goal‐ordering (FGO) constraints. In automated planning, forward search with FGO constraints has been proposed many times over the years, but there are still major difficulties in realizing these FGOs in plan generation. Many existing methods such as goal agenda manager and ordered landmarks cannot detect the FGOs accurately, and thus, the undiscovered ordering relationship may cause the forward search to suffer from deadlocks. In this article, we put forward an approach via an effective search heuristic to constrain a planner to satisfy the FGOs. We make use of an atomic goal‐achievement graph in a look‐ahead search under the FGO constraints. This allows a forward search strategy to plan forward efficiently in multiple steps toward a goal state along a search path. Experimental results illustrate that, by avoiding deadlocks, we can solve more benchmark planning problems more efficiently than previous approaches. We also prove several formal properties for search that are related to FGO detection.
Farewell to an old friend: chest X‐ray vs high‐resolution computed tomography in welders' lung disease
Authors: Tutkun Engin , Abusoglu Sedat , Yilmaz Hinc , Gunduzoz Meside , Evcik Ender , Ozis Türkan Nadir , Keskinkilic Bekir , Unlu Ali
Published: October 2013

Introduction

Welder's lung disease originated from a mixed exposure to different kinds of metals and chemicals from welding fumes. Because of these various harmful effects, irreversible morphological changes may occur in all parts of the respiratory tract, airways and lung parenchyma. Parenchymal changes are the main lesions that define the severity of exposure. The grade of these lesions is the main criteria for compensation claims and the clinical threshold for the occupational health physician's decision making of work change in order to protect the worker's health. In this study, our aim was to compare the diagnostic performance of chest X‐ray (CXR) and high‐resolution computed tomography (HRCT) for welders' lung disease.

Objectives

Seventy‐four male welders aged between 25 and 55 years were enrolled to this study.

Methods

Clinical diagnoses were compared by CXR and HRCT. Same radiologists evaluated the scans without any knowledge about the medical history of the patient (double‐blinded evaluation). The agreement between radiologists was compared with Cohen's kappa statistics.

Results

The mean age for 74 welders was 40.7 years. The mean duration of exposure was 18.9 years. Although all were found to be nonpathological on the CXR, 27 mild nodular and nine mild linear opacities, five emphysematous changes, three ground glass infiltrates and one pleural thickening were detected by HRCT.

Conclusions

HRCT provides better diagnostic performance compared to CXR for the diagnosis of welders' lung disease.
Parasitoid genus‐specific manipulation of orb‐web host spiders (Araneae,Araneidae)
Authors: KORENKO STANISLAV , ISAIA MARCO , SATRAPOVÁ JITKA , PEKÁR STANO
Published: October 2013

Araneid spiders of genusAraniellaare attacked by three polysphinctine parsitoid waspsPolysphincta boopsTschek,P. tuberose(Gravenhorst), andSinarachna pallipes(Holmgren). In the present study, the trophic niche of sympatrically occurring parasitoids and the host manipulation they induced were studied. The aim was to identify whether the variation in host response to manipulation is as a result of differences among parasitoids or among host species.

It was found that final instar larva forced the spider host to build athree‐dimensional(3D) ‘cocoon web’ to protect the parasitoid during pupation. The behaviour of parasitoid larva and the induced modification of the web architecture differed between wasps of genusPolysphinctaandSinarachnabut not among three spider species. The larvae of genusPolysphinctaforced the spider host to build the ‘cocoon web’ with a high thread density within which the pupa was positioned horizontally. The larvae ofSinarachnaforced the spider host to build web with sparse threads and the pupa was positioned vertically in the middle of the ‘cocoon web’.

There seems to be an investment trade‐off in parasitoid wasps: some species manipulate the host to build a dense protective web, while pupating in a sparse cocoon, whereas others make the spider produce a sparse web but build a dense pupa wall.
Faecal worm egg count analysis for targeting anthelmintic treatment in horses: Points to consider
Authors: Lester H. E. , Matthews J. B.
Published: October 2013

Equine gastrointestinal nematodes are ubiquitous; in horses that graze contaminated pasture and that are not treated appropriately, large numbers of worms can accumulate, which can lead to serious clinical disease. Nematode control has traditionally followed interval treatment regimens, which involve regular anthelmintic administration to all horses based on the strongyle egg reappearance periods of each drug, usually defined around the time of licensing. Interval treatment programmes have resulted in substantial reductions in large strongyle disease, but have made major contributions to the development of anthelmintic resistance, particularly in cyathostomins. Cyathostomin resistance to 2 of the 3 available anthelmintic classes is widespread, and resistance to both classes in single populations is not uncommon. Reduced efficacy of the most commonly used macrocyclic lactone anthelmintics, as measured by shortened egg reappearance periods after treatment, is emerging in cyathostomins. Macrocyclic lactone resistance is also now commonly reported in Parascaris equorum on stud farms. Faecal worm egg counts (FWEC) are increasingly being used as part of targeted approaches to parasite control, whereby only those horses with moderate to high FWEC within a group are treated with an anthelmintic. The objective of this approach is to reduce environmental contamination, while leaving a proportion of the worm population in some horses unexposed to selection pressure for anthelmintic resistance. This article reviews recent findings in equine parasitology research that will underpin guidelines for control, with a particular focus on how to optimise the value of FWEC methodologies and anthelmintic efficacy analyses.
Dynamics and limitations of phytoplankton biomass along a gradient inMwanzaGulf, southernLakeVictoria (Tanzania)
Authors: Cornelissen I. J. M. , Silsbe G. M. , Verreth J. A. J. , van Donk E. , Nagelkerke L. A. J.
Published: October 2013

We investigated how dynamics in phytoplankton biomass are driven through light and nutrient limitations in theMwanzaGulf,LakeVictoria (Tanzania).

We measured light attenuation, chlorophyllaand water quality parameters along a phytoplankton biomass gradient in theMwanzaGulf at six sampling stations in three different seasons fromAugust 2009 toMarch 2011.

We found a higher rate of attenuation of photosynthetic available radiation than in other gulfs ofLakeVictoria which could only partially be explained by phytoplankton biomass, measured as chlorophylla. Suspended particulate detritus strongly affected light attenuation, particularly in shallow water.

In shallow water in the southern part of theMwanzaGulf, nutrients were in excess and phytoplankton biomass was limited by light. In deeper water near the entrance of the gulf, light was not limiting when nitrogen probably was, as indicated by theN:Pratio.

Low abundance ofN‐fixing phytoplankton species suggests thatN‐fixation was low in shallow water. Phytoplankton biomass was lower inMwanzaGulf than in northern gulfs ofLakeVictoria, but might increase in the future as a result of nutrient enrichment caused by an increase in intensive agriculture and rapid growth of the city ofMwanza.
Efficacy of oral powder compared with chewable tablets for lanthanum carbonate administration in hemodialysis patients
Authors: Sakurada Tsutomu , Oishi Daisuke , Shibagaki Yugo , Yasuda Takashi , Kimura Kenjiro
Published: October 2013

Lanthanum carbonate (LC) has been administered in a chewable tablet form for patients with hyperphosphatemia undergoing dialysis. However, some patients have difficulty chewing the tablets. LC oral powder has recently been released in Japan. The purpose of this study was to clarify the efficacy of LC oral powder form compared with that of chewable tablet form. The efficacy and safety of LC oral powder was retrospectively assessed in hemodialysis patients who switched from chewable tablet form to oral powder form without dose modification. Thirty‐six patients (mean age, 66.8 ± 10.5 years; male, 64%; 39% with diabetes; mean duration of dialysis treatment, 99.2 ± 95.6 months) were enrolled in this study between June and July of 2012. Changes in clinical data and adverse events after the switch to oral powder form were investigated. The average dose of LC was 1180 ± 520 mg/day. Serum phosphorus levels were significantly decreased after the switch from chewable tablet form to oral powder form (5.3 ± 1.7 mg/dL at baseline vs. 4.9 ± 1.2 mg/dL at after 1 month after, P = 0.038). In contrast, no significant differences were observed in serum calcium and parathyroid hormone levels. Furthermore, no significant differences were evident in weight gain after the switch to oral powder form (2.5 ± 1.2 kg at baseline vs. 2.4 ± 1.1 kg at 1 month after the switch, P = 0.29). No serious adverse events were recorded. Our results suggest that LC is more effective in oral powder form than chewable tablet form for hemodialysis patients.
Impact of Biventricular Pacing on Mortality in a Randomized Crossover Study of Patients with Heart Failure and Ventricular Arrhythmias
Authors: LOZANO IGNACIO , BOCCHIARDO MARIO , ACHTELIK MICHAEL , GAITA FIORENZO , TRAPPE HANS‐JOACHIM , DAOUD EMILE , HUMMEL JOHN , DUBY CHRISTIAN , YONG PATRICK ,   On behalf of the VENTAK CHF/CONTAK CD INVESTIGATORS STUDY GROUP
Published: October 2013

Biventricular (BV) pacing is under clinical investigation for the treatment of heart failure. Its impact on mortality is unknown. Patients with heart failure and ventricular tachyarrhythmias received an implantable cardioverter defibrillator with BV pacing capability. Patients were randomized 1:1 to BV pacing or no pacing, then crossed over to the alternate mode after 3 months. All‐cause mortality was measured in each arm up to the point of crossover. Fifteen of 222 patients died between implant and crossover. Five patients died while programmed to BV pacing and 19 died while programmed to no pacing. Survival in the BV pacing arm was 93 ± 4% versus 86 ± 6% in the no pacing arm (P = 0.18). In a patient population with symptomatic heart failure and ventricular arrhythmias, BV pacing does not appear to be associated with excess mortality. Larger and longer studies will be needed to determine if BV pacing confers a survival benefit.
Prevalence of Potential Candidates for Biventricular Pacing Among Patients with Known Coronary Artery Disease: A Prospective Registry from a Single Center
Authors: DE SUTTER JOHAN , DE BONDT PIETER , VAN, DE WIELE CHRISTOPH , FONTEYNE WINOC , DIERCKX RUDI , CLEMENT DENIS , TAVERNIER RENE
Published: October 2013

A Prospective Registry from a Single Center. New forms of ventricular pacing are increasingly studied as an option in the management of patients with heart failure. Coronary artery disease (CAD) is the most frequent cause of heart failure, and patients with complete left or right bundle branch block (LBBB and RBBB) and a reduced left ventricular ejection fraction (LVEF) are the best candidates for this new therapy. However, the prevalence of this clinical presentation is uncertain. During a 1‐year period, 433 patients with documented CAD (mean age 64 ± 10 years, 79% men) who were referred for myocardial perfusion imaging were prospectively studied. All patients underwent a 2‐day stress‐rest gated 99mTc‐Tetrofosmin SPECT study with evaluation of resting LV enddiastolic (LVEDV) and endsystolic (LVESV) volumes and LVEF. The resting ECG was examined in all patients for the presence of complete LBBB or RBBB. Of the 433 patients with CAD 36 patients (8.3%) had LBBB (n = 14) or RBBB (n = 22) and a QRS width >120 ms. These 36 patients were in general older and more frequently had diabetes and atrial fibrillation. Patients with LBBB or RBBB had a significantly lower LVEF (41 ± 16%vs 48 ± 14%, P < 0.01) and significantly higher LV volumes compared to patients without LBBB or RBBB (177 ± 79 mL vs 131 ± 53 mL, P < 0.001 for LVEDV and 116 ± 76 mL vs 73 ± 49 mL, P < 0.001 for LVESV). In total, 112 /433 (26%) had an LVEF ≤ 40%; 16 had also a LBBB or RBBB (3.7% of the whole population, 14% of the patients with a LVEF ≤ 40%). Within the group of patients with a LVEF ≥ 40%, patients with BBB had comparable LVEF (26 ± 9% vs 30 ± 8%, P = NS) but significantly higher LVEDV and LVESV (230 ± 70 mL vs 190 ± 64 mL, P < 0.05 for LVEDV and 170 ± 65 mL vs 135 ± 56 mL, P < 0.05 for LVESV). In this prospective registry 3.7% of all patients with known CAD had LBBB or RBBB in combination with a LVEF ≤ 40%. This represented 14% of all patients with a LVEF ≥ 40%. These limited numbers should be kept in mind when considering biventricular pacing as a new therapeutic options in patients with heart failure.
Reversal of Left Ventricular Remodeling by Synchronous Biventricular Pacing in Heart Failure
Authors: LAU CHU‐PAK , YU CHEUK‐MAN , CHAU ELAINE , FAN KATHRYN , TSE HUNG‐FAT , LEE KATHY , TANG MAN‐OI , WAN SIU‐HONG , LAW TIN‐CHU , LEE PUI‐YIN , LAM YUI‐MING , HILL MICHAEL R.S.
Published: October 2013

Synchronous biventricular pacing is a new nonpharmacological supplemental treatment of advanced heart failure associated with electromechanical conduction delay. However, the role of pacing on left ventricular remodeling is unknown. Eleven patients with New York Heart Association Class III to IV heart failure, a left ventricular ejection fraction < 35%, and a QRS duration ≥ 140 ms received a biventricular dual chamber pacemaker. Serial echocardiography, 6‐minute hall walk, and Minnesota Living with Heart Failure quality‐of‐life (QOL) questionnaire were performed before and after up to 3 months of pacing. At 3 months there was a significant increase in fractional shortening (P < 0.001), ejection fraction (P < 0.001), and cardiac output (P < 0.05). The left ventricular end‐diastolic volume (245 ± 70 vs 185 ± 37 mL, P < 0.05), end‐systolic volume (209 ± 69 vs 140± 44 mLP < 0.05), and mitral regurgitation were reduced (P < 0.05), and diastolic filling time was lengthened (P < 0.05). There were also improvements in heart failure symptoms, an increase in 6‐minute walk distance, and a decrease in QOL scores. Synchronous biventricular pacing for 3 months was associated with hemodynamic improvements, reversal of left ventricular remodeling, and increase in left ventricular systolic function, and a decrease in secondary mitral regurgitation.
Biventricular Pacing in Severe Heart Failure Patients Reverses Electromechanical Dyssynchronization from Apex to Base
Authors: TOUSSAINT JEAN‐FRANÇOIS , LAVERGNE THOMAS , OLLITRAUT JACKY , HIGNETTE CHANTAL , DARONDEL JEAN‐MARC , DE DIEULEVEULT BARBARA , FROISSART MARC , HEUZEY JEAN‐YVES LE , GUIZE LOUIS , PAILLARD MICHEL
Published: October 2013

Biventricular (BV) pacing is an emerging treatment for patients with severe dilated cardiomyopathy and ventricular asynchrony. Radionuclide angioscintigraphy has shown that BV can reduce activation delays between left (LV) and right ventricles (RV), but alterations of electromechanical asynchrony between the LV base and apex have not been previously described. Radionuclide angioscintigraphy with Tc99m red cell labeling was performed in 21 patients, 64 ± 17 years of age, in NYHA functional Class III or IV, and with a mean QRS duration of 180 ± 15 ms. Right (RVEF) and LV ejection fraction (LVEF), and the synchronization between LV apex and base (Tab) in the left lateral view, were measured by a phase analysis program (1) at baseline, (2) on day 8 after BV pacemaker implantation (D8), and (3) at 12‐month follow‐up in BV (M12). BV pacing reversed Tab from 42 ± 47 ms at baseline to −57 ± 75** on D8, and −37 ± 76** on M12. LVEF increased from 17.8 ± 6.3% to 19.9 ± 8.3 on D8, and 24.2 ± 10.8* on M12, and RVEF increased from 27.6 ± 16% to 29.9 ± 16 on D8 and 34.1 ± 12.1* on M12 (*P < 0.05, **P < 0.001). A close correlation was found between early LV apex‐to‐base resynchronization induced by BV and late increase in LVEF (r = 0.59**). In parallel with its known interventricular resynchronization effect, BV pacing reverses the apex‐to‐base ventricular activation sequence, causing early contraction of the LV base followed by the apex. These changes persisted up to 12 months along with an improvement in LV systolic function.
Which is the Optimal Testing Method for Identifying an AV Delay that Allows Intrinsic Conduction?
Authors: EGUÍA LUIS E. , PINSKI SERGIO L. , HAW JANET , TROHMAN RICHARD G.
Published: October 2013

It is desirable to maintain normal, conducted ventricular activation in patients with dual‐chamber pacemakers and preserved atrioventricular (AV) conduction. The shortest AV delay resulting in consistent ventricular inhibition (avoiding ventricular pseudofusion) was determined by a conventional incremental (inside‐out) technique vs the alternate decremental (outside‐in) technique in 20 such patients. Determinations were made in VDD mode in 20 patients and DDD mode (∼10 beats/min faster than the intrinsic rate) in 19. In VDD mode, the shortest AV delay avoiding ventricular pseudofusion was never found during inside‐out testing. It was identical with both methods in 10 patients (50%), and shorter by 10–80 ms (mean 20 ± 20 ms) with the outside‐in method in the remaining 10 (P = 0.004). In DDD mode, the shortest AV delay resulting in consistent ventricular inhibition was found only once during inside‐out testing. It was the same with both methods in 13 patients (68%), and shorter by 10–20 ms (mean 14 ± 5 ms) with the outside‐in method in the remaining 5 (26%, P = 0.18; Fisher's exact test). The shortest sensed AV delay preventing ventricular pseudofusion is most likely to be found with a decremental method (outside‐in). In rare patients, it identifies AV delays resulting in inhibition, while ventricular pacing persists at longer programmable AV delays with the conventional inside‐out approach.
Neurohumoral Behavior in Recipients of Cardiac Pacemakers Controlled by a Closed‐Loop Autonomic Nervous System‐Driven Sensor
Authors: FILHO MARTINO MARTINELLI , NISHIOKA SILVANA A.D. , LOPES HENO , OLIVEIRA JÚLIO C. , PEDROSA ANISIO A. , SIQUEIRA SERGIO F. , COSTA ROBERTO
Published: October 2013

The purpose of a sensor‐driven pacing system is to physiologically correct chronotropic incompetence (CI). The aim of this study was to evaluate the changes in heart rate provided by a sympathetically driven pacemaker (PM) compared with normal sinus function (NSF). Nine men and six women (age 37–80 years) with AV block and a PM controlled by a closed‐loop system were studied. Group I included eight patients with CI, and group II included seven patients with NSF. All patients underwent Valsalva maneuver and tilt table testing with measurements of plasma catecholamines and renin activity. Pacing was initially programmed in the DDDC mode at a lower rate (60 ppm) and upper rate limit (0.85 × [220 ‐ age]), then in DDDR in group I and VVIR in group II. The second phase of the study consisted of nitroglycerin and phenylephrine infusions, and the third phase of physiological provocative maneuvers. The second and third phases were performed in three patients from each group with sensor activity On and Off. In group I, heart rate changed during tilt only in the DDDR mode. In group II, heart rate changes were comparable in both modes. Catecholamine levels in group I were higher during DDDC than during DDDR pacing (P < 0.05). In group I, heart rate did not change during phases II and IV of the Valsalva maneuver in the DDDC mode, but behaved nearly physiologically after sensor activation. A late and a paradoxical response to nitroglycerin was observed in groups I and II and to phenylephrine in group I. During physiological maneuvers, significantly greater variations in heart rate were observed during DDDR than during DDDC pacing. Sympathetic SDP provides physiological modulations of the heart rate were provided by a sympathetically driven pacing system in patients with AV block and CI.
Benefits in Projected Pacemaker Longevity and in Pacing Related Costs Conferred by Automatic Threshold Tracking
Authors: BORIANI GIUSEPPE , BIFFI MAURO , BRANZI ANGELO , MININNO ANTONIO , SIGLIANO RICCARDO ,   ON BEHALF OF THE PACEMATE STUDY GROUP
Published: October 2013

The aim of this study was to calculate the battery current drain of different VVI‐VVIR pulse generators, with and without automatic adjustment of stimulation output, from the same manufacturer, and obtain projections on pacemaker longevity and pacing related costs. Twenty‐five patients who had received a VVIR pacemaker (Microny SR + 2425T) with Autocapture function, an algorithm able to provide automatic adaptation of device output coupled with continuously monitored capture threshold, were analyzed. Calculations of current drain and projections of device longevity were based on diagnostic data retrieved from device memory and on comparisons of multiple programmed settings of the same device (Microny SR + 2425T with Autocapture, Low Output [output = 2 × Autocapture threshold, but not less than 2.4 V] versus Standard Output [5 V]). In addition, devices with Autocapture but with different battery capacities (0.35 Ah and 0.79 Ah, Microny and Regency, respectively) were compared to a standard device (battery capacity = 0.78 Ah) at 2.5‐V and 5‐V output settings. According to a series of assumptions, Autocapture increased device longevity by 53% (Microny) and by 245% (Regency) over a 15‐year follow‐up with a consequent reduction in pacing related costs of 25% (Microny) and of 57% (Regency) compared to the standard settings of a VVIR device from the same manufacturer. In conclusion, pacing with constant adaptation of generator output coupled with continuous monitoring of stimulation threshold has the potential to increase generator longevity and to reduce pacing related costs as compared to a standard device from the same manufacturer.
Cardioinhibition During Tilt Testing Identifies Patients Who May Benefit from Pacing
Authors: KURBAAN ARVINDER S. , FRANZÉN ANN‐CHRISTINE , HEAVEN DAVID , MATHUR GITA , BOWKER TIMOTHY J. , PETERSEN MARK , SUTTON RICHARD
Published: October 2013

This study examined whether the various hemodynamic collapse patterns observed during tilt testing in patients with suspected neurocardiogenic syncope are relevant when planning therapy, particularly whether a predominantly cardioinhibitory response predicts a beneficial response from pacing. Methods: The effects of temporary atrioventricular (A‐V) sequential pacing were studied during tilt testing in 34 patients 48.2 ± 18.5 years of age. The patient population was divided into a cardioinhibitory group (VASIS classes 2A and 2B) or mixed group (VASIS classes 1 and 3) according to their response to baseline tilt testing. The test was then repeated during A‐V pacing with rate hysteresis. A positive response to A‐V pacing was defined as a ≥ 30‐second increase between onset of symptoms and syncope, or mitigation of symptoms compared with the baseline tilt test. Results: The study protocol was not successfully completed in three patients. Among the remaining 31 patients, a baseline cardioinhibitory response was observed in 17, and a mixed response in 14 patients. A‐V sequential pacing was successful in 13 of 17 patients with a cardioinhibitory response versus 5 of 14 patients with a mixed response (P = 0.024). Conclusion: The presence of a predominantly cardioinhibitory collapse pattern (VASIS 2A and 2B) during baseline tilt testing doubled the likelihood of successful temporary A‐V sequential pacing, and may identify patients with neurocardiogenic syncope most likely to benefit from permanent dual chamber pacing.
Diagnostic Value of Stored Electrograms in Single‐Lead VDD Systems
Authors: ISRAEL C. W. , GASCON D. , NOWAK B. , CAMPANALE G. , PASCOTTO P. , HARTUNG W. , LELLOUCHE D. ,   On behalf of the Pulsar/Selute Picotip VDD Study Group
Published: October 2013

Evaluation of the quality of atrial sensing is indispensable to monitor the performance of VDD single‐lead systems. In addition to counters, a new VDD system offers storage of intracardiac electrograms (EGMs), The clinical contribution of stored EGMs in a VDD pacemaker was prospectively examined in a multicenter study, and the reliability of its counters was evaluated on the basis of EGM information. Methods: A VDD system (Pulsar 870, Guidant Co.) was implanted in 46 patients with atrioventricular block. EGM storage was activated upon detection of ventricular tachycardia (VT), recurrent premature ventricular complexes (PVCs), and mode switch (“atrial tachy reaction,” ATR). Stored EGMs were retrieved before discharge of the patients from the hospital, and at 6‐week, 3‐month, and 6‐month follow‐up. Results: A total of 440 stored EGMs were retrieved and analyzed. Of 30 VT episodes detected, 2 (7%) were confirmed, and all others were attributable to ventricular oversensing. One postmortem interrogation documented VT as the cause of sudden death. Of 175 EGMs stored upon detection of PVCs, 43 episodes (25%) were confirmed and 124 (70%) showed intermittent atrial undersensing with spontaneous AV conduction; in 8 episodes (5%) no abnormality was observed. Of 235 episodes stored upon ATR, 82 (35%) were confirmed and 153 were due to atrial oversensing. Conclusions: (1). Stored EGMs indicated a high percentage (69%) of event misdiagnoses by the pacemaker. Thus, pacemaker counter information without the availability of stored EGMs should be interpreted with caution. (2). Misclassified events are of high clinical importance since they unmask otherwise unsuspected intermittent under‐ or oversensing.
Role of Rapid Focal Activation in the Maintenance of Atrial Fibrillation Originating from the Pulmonary Veins
Authors: KUMAGAI KOICHIRO , YASUDA TOMOO , TOJO HIDEAKI , NOGUCHI HIROO , MATSUMOTO NAOMICHI , NAKASHIMA HIDEKO , GONDO NAOKI , SAKU KEIJIRO
Published: October 2013

Most episodes of focal atrial fibrillation (AF) can be initiated by premature beats originating from the pulmonary veins (PV). However, the role of rapid focal activation in the maintenance of AF is unclear. Thirty‐two patients with focal AF who underwent focal ablation of triggering ectopic beats were studied. Bipolar electrograms from all four PVs were recorded simultaneously. The cycle length (CL) of RFA at sites that triggered AF was measured at AF onset, after 5 minutes of sustained AF, and just before the spontaneous termination of 32 episodes of nonsustained AF. Fifteen episodes of sustained AF (> 10 minutes) and 17 episodes of nonsustained AF (5–120 seconds, mean 56 ± 59 seconds) were analyzed. In sustained AF, the mean CL of RFA in the PV from which it originated was not significantly different than in the other PVs, and RFA was continuously observed. In nonsustained AF, the mean CL of RFA in a PV from which it originated was significantly shorter than in other PVs and, when RFA disappeared, AF terminated. RFA in 1 PV induced RFA in another PV. In conclusion, widespread conduction of RFA from a PV at its source to the other sites may be necessary for the sustenance of AF. A PV interaction, a RFA triggering another, may be involved in the maintenance of AF. RFA arising from PVs is important not only as a trigger of onset, but also in the maintenance of AF.
Multiple Sources Initiating Atrial Fibrillation from a Single Pulmonary Vein Identified by a Circumferential Catheter
Authors: HOCINI MÉLÈZE , HAÏSSAGUERRE MICHEL , SHAH DIPEN , JAÏS PIERRE , PENG JING TIAN , YAMANE TEIICHI , DEISENHOFER ISABEL , GARRIGUE STÉPHANE , FUIMAONO KRISTINE , PIKE ROB , CLÉMENTY JACQUES
Published: October 2013

The pulmonary veins are the predominant source of ectopic activity initiating AF. The reproducibility of intrapulmonary vein activation during ectopic activity and/or initiation of multiple AF episodes was examined. Eighty‐nine pulmonary veins (PVs) among 29 patients undergoing radiofrequency ablation of AF were studied with a 15‐ to 20‐mm diameter, circumferential PV catheter equipped with ten electrodes and a deflectable shaft. Local electrograms were recorded simultaneously during sinus rhythm, ectopic activity, or AF onset, spontaneously or induced via the catheter left in a stable position. Fifty‐four arrhythmogenic veins were identified, 39 showing isolated ectopy, and 8 displayed repetitive ectopy (in salvos). The earliest site of activation and the sequence of intra‐PV activation during isolated ectopy was identical to that observed during consecutive ectopic complexes in 77% and variable in 23% during isolated ectopy. The earliest activity was sometimes limited to a single bipole. During repetitive ectopy and AF initiation, multiple sources and/or variable activation patterns were noted in 53% of instances, indicating the presence of multiple arrhythmogenic foci within the same PV. Simultaneous electrogram recordings with a circumferential PV catheter identified the presence of multiple arrhythmogenic foci within a single PV.
Treatment of Mixed Atrial Fibrillation and Typical Atrial Flutter by Hybrid Catheter Ablation
Authors: KUMAGAI KOICHIRO , TOJO HIDEAKI , YASUDA TOMOO , NOGUCHI HIROO , MATSUMGTO NAOMICHI , NAKASHIMA HIDEKO , GONDO NAOKI , SAKU KEIJIRO
Published: October 2013

Successful isthmus ablation of typical atrial flutter mixed with atrial fibrillation (AF) may favorably modify the subsequent course of paroxysmal AF. However, the source of ectopic beats triggering AF may be located in the pulmonary veins (PV). This study compared the results of combined isthmus and focal ablation with ablation limited to the isthmus in patients with mixed AF and typical atrial flutter. Thirty patients with typical atrial flutter and AF were treated. Ablation limited to the isthmus was performed in 14 patients (group A), and 16 patients underwent focal ablation of triggering ectopic beats combined with isthmus ablation (group B). Successful linear ablation of the isthmus was accomplished in all patients. In group A, AF was eliminated in 4 patients (29%) after isthmus ablation. In group B, the origin of 26 foci triggering AF (1 focus in 38% of patients, 2 foci in 31 %, 3–4 foci in 31 %) was found in the PV in 93% (left superior: 46% left inferior: 21%, right superior: 25%) and the right atrium in 7% of instances. AF was eliminated in 11 patients (69%) after ablation of these foci. The success rate in group B was significantly higher than in group A (P < 0.05). In conclusion, in cases of mixed AF and typical atrial flutter, episodes of AF originated from PV foci in >90% of instances. These findings suggest that isthmus ablation combined with PV focal ablation may be effective in mixed AF and typical atrial flutter.
Noncontact System‐Guided Simplified Right Atrial Linear Lesions Using Radiofrequency Transcatheter Ablation for Treatment of Refractory Atrial Fibrillation
Authors: GASPARINI MAURIZIO , COLTORTI FERNANDO , MANTICA MASSIMO , GALIMBERTI PAOLA , CERIOTTI CARLO , BEATTY GRAYDON
Published: October 2013

This article describes our experience with a staged “hybrid” approach to the treatment of drug resistant AF, in which the completeness of a single linear lesion in the RA was verified with a noncontact mapping system. Inferior vena cava‐tricuspid annulus ablation was performed and followed by the creation of a single intercaval lesion. The study population consisted of 24 patients with a 3.4 ± 1.6‐year history of drug resistant, severely symptomatic, lone paroxysmal (n = 19), or persistent (n = 5) AF. During a follow‐up of 8 ± 2.6 months, 12 (50%) patients remained asymptomatic and 6 (25%) had a significant decrease in AF episodes, while the arrhythmia was unchanged in 5 (21 %) patients and aggravated in 1 (4%) patient. Overall, a favorable clinical result was achieved in 18 (75%) patients.
Comparison of Pulsed Versus Continuous Radiofrequency Energy Delivery: Diameter of Lesions Induced with Multipolar Ablation Catheter
Authors: ERDOGAN ALI , CARLSSON JOERG , ROEDERICH HANS , SCHULTE BRITTA , SPERZEL JOHANNES , BERKOWITSCH ALEXANDER , NEUZNER JOERG , PITSCHNER HEINZ F.
Published: October 2013

The aim of this study was to compare the efficacy of pulsed versus continuous RF energy delivery via multipolar ablation catheters. In vitro tests were performed in endomyocardial preparations of fresh bovine hearts in a bath of physiological saline solution (37°C) at constant flow conditions (1.5 L/min). The catheters were applied to the endocardium at a constant pressure. Energy was delivered pulsed (to 4 electrodes simultaneously, 5‐ms duty cycle) or continuously (to each electrode separately). In vivo experiments were performed under fluoroscopy in eight anesthetized pigs, guided by endocardial electrograms to place the catheters in 22 different intraatrial positions. Lesion volume was calculated from measurements of the lesion diameter with a microcaliper. The homogeneity of the lesions was classified from 1 (highest) to 4 (least). More homogeneous linear lesions were produced in significantly less time with pulsed than with continuous energy delivery. There were no differences in electrode temperature or impedance values in vitro and in vivo. The results in the in vitro experiments were reproducible in the intact animal experiments. Significantly larger and more homogeneous linear lesions were created more rapidly with pulsed than with continuous energy delivery.
Efficacy and Safety of Transvenous Atrial Cardioversion in Patients with Mitral Valve Disease and Long‐standing Atrial Fibrillation
Authors: GRÖNEFELD GERIAN C. , LI YI‐GANG , BOGUN FRANK , HOHNLOSER STEFAN H.
Published: October 2013

Background: Transvenous internal cardioversion (ICV) of atrial fibrillation (AF) may be successful after unsuccessful external CV. However, the safety and efficacy of ICV in patients with significant mitral valve disease and AF of long duration have not been evaluated prospectively. Methods: This study included 22 consecutive patients (mean age = 59 ± 14 years, 12 women) with mitral regurgitation grade = II (n = 14) or after mitral valve replacement (n = 8), who underwent ICV with 3/3 ms biphasic shocks delivered via two defibrillation catheters placed in the right atrium and the coronary sinus, respectively. The mean left atrial diameter was 53 ± 7 mm (range 45–68), and AF had been diagnosed for a median of 24 months. All patients received oral amiodarone pretreatment followed by a maintenance dose of 200 mg/day. Results: Sinus rhythm (SR) was restored by ICV in 15/20 patients (75%), and returned spontaneously in two patients during amiodarone pretreatment. The mean threshold for ICV was 6.2 ± 3.5 J. Sinus node disease was present in one patient after ICV, and two patients developed amiodarone‐induced hyperthyroidism. During a follow‐up of 11 ± 5 months, 8 patients had recurrent AF. The remaining 11 patients who were successfully cardioverted remained in stable SR. Conclusion: SR can be safely and successfully restored by ICV in patients with MVD and longstanding AF. During intermediate‐term follow‐up, a significant proportion of patients remained in SR with oral amiodarone therapy.
Predictors of Atrial Defibrillation Threshold in Internal Cardioversion
Authors: BORIANI GIUSEPPE , BIFFI MAURO , CAMANINI CLAUDIA , BACCHI LETIZIA , ZANNOLI ROMANO , LUCERI RICHARD , BRANZI ANGELO
Published: October 2013

This study examined the clinical, echocardiographic, and electrophysiological factors influencing the atrial defibrillation threshold (ADFT) in patients with chronic, persistent AF undergoing transvenous, low energy, atrial cardioversion. Twenty‐two patients (age 57 ± 15 years) with a mean AF duration of 7.8 ± 7.1 months (range 2–32 months) underwent internal cardioversion with catheters placed in the right atrium and coronary sinus. Biphasic shocks (3/3 ms) were delivered in a step‐up protocol. ADFT was defined as the lowest energy shock that converted AF to sinus rhythm. All patients were successfully cardioverted at a mean ADFT of 5.62 ± 2.82 J (range 2.6–12.9 J). Fifteen variables, including clinical characteristics (age, body mass index, AF duration, etiology), echocardiographic measurements (atrial diameter and volumes, indexes of ventricular performance), hemodynamic measurements, and mean atrial cycle during AF were analyzed as possible predictors of ADFT. In univariate regression analysis, AF duration, mean RR interval, and cardiac index correlated with ADFT. In multivariate regression analysis, AF duration remained as the only significant predictor of ADFT (B coefficient 0.311, P < 0.001; 95% confidence interval [CI] 0.194‐0.427). AF duration was the most powerful predictor of ADFT. It should be considered when planning internal CV of AF to limit the number of shocks delivered. Furthermore, long intervals between AF onset and CV should be avoided.
Multiple AV Nodal Pathways with Multiple Peaks in the RR Interval Histogram of the Holter Monitoring ECG during Atrial Fibrillation
Authors: WEISMÜLLER PETER , BRAUNSS CAROLINE , RANKE CARSTEN , TRAPPE HANS‐JOACHIM
Published: October 2013

Two or more peaks on the 24‐hour electrocardiogram (ECG) RR interval histogram of patients with atrial fibrillation suggests the presence multiple AV nodal pathways. The prevalence of multiple AV nodal pathways in this population is unknown. The study included 250 patients with permanent atrial fibrillation during 24‐hour ECG. The number of peaks on the RR interval histogram was measured in each patient. A single peak was present in 153 patients (61%), 80 patients (32%) had two peaks, 13 patients (5%) had three, and 4 patients (2%) had four peaks. Among the 97 patients (39%) with >1 AV nodal pathway, the estimated mean heart rate reduction by hypothetical ablation of all supernumerary AV nodal pathways with short refractory periods was 16 beats/min, from 82 to 65 beats/min. Among the overall population, 16 patients (6%) with >1 AV nodal pathway had a mean heart rate >100 beats/min. In this subgroup, modulation of AV node conduction by hypothetical ablation of all supernumerary AV nodal pathways with short refractory periods yielded an estimated reduction in mean heart rate of 26 ± 15 beats/min, from 110 ±9 beats/min to 84 ± 14 beats/min (P < 0.01), a 23% decrease. The presence of >1 AV nodal pathway was suspected in 39% of all patients with permanent atrial fibrillation. The hypothetical ablation of all supernumerary AV nodal pathways with short refractory periods resulted in a clinically significant reduction in heart rate in 6% of patients in this population.
Implantation and Follow‐Up of ICD Leads Implanted in the Right Ventricular Outflow Tract
Authors: LUBINSKI ANDRZEJ , LEWICKA‐NOWAK EWA , KRÓLAK TOMASZ , KEMPA MACIEJ , BIELAWSKA BEATA , WILCZEK RAJMUND , SWIATECKA GRAZYNA
Published: October 2013

Unipolar ICD electrodes are routinely implanted at the right ventricular apex (RVA). However, inappropriate pacing/sensing parameters and/or high DFT may limit the appropriateness of the lead's implantation at the RVA. This study examined the effects on DFT of ICD leads implanted in the RVOT, attached to the high interventricular septum as an alternate location. DFT, defibrillation impedance, and sensing and pacing characteristics were measured at the time of implantation in 28 consecutive patients. Group A consisted of 12 patients in whom the ICD implantation criteria in the RVA were not satisfied, and whose lead was placed in the RVOT. Group B consisted of 16 patients with ICD electrodes implanted at the RVA. Mean DFT in group A was 11 ± 4 J (4.5–20 J) versus 12 ± 6 J (4–20 J) in the group B (P = 0.58). Defibrillation impedance was 81 ± 9 Ω (69–92 Ω) in group A versus 77 ± 15 Ω (46–93 Ω) in group B (P = 0.43). R wave amplitude, slew rate, pacing threshold, and pacing impedance were comparable in both groups. In the perioperative period, the electrode needed to be repositioned in two patients from group A. There was no further dislodgment of RVOT defibrillation leads or other lead related complications during a follow‐up of 23 ± 9 months. The placement of ICD leads in the RVOT is an alternative to the RVA position. However, active‐fixation ICD leads should be considered to limit the risk of electrode dislodgment.
Tissue Oximetry for the Diagnosis of Neurally Mediated Syncope
Authors: SINGER IGOR , EDMONDS HARVEY L.
Published: October 2013

This study examined the potential clinical contribution of noninvasive brain and skeletal muscle oximetry as a diagnostic aid in neurally mediated syncope. Tilt table testing was performed in 15 patients with a history of syncope and 9 healthy volunteers. Spatially resolved reflectance near‐infrared spectroscopy was used to examine regional oxyhemoglobin saturation in the frontal cerebral cortex and pectoral muscle. During upright tilt, syncope occurred in four patients. Each episode was associated with bradycardia, hypotension, and brain oxygen desaturation of > 20% from the supine reference baseline, while the largest desaturation in non‐syncopal patients was 13%. In two syncopal patients, a sudden increase in pectoral oxygen saturation preceded cerebral oxygen desaturation and unconsciousness, suggesting a sudden loss of peripheral sympathetic tone. Simultaneous desaturation in both tissues in the other two patients appeared to be in response to a diminished cardiac output. The muscle and brain oxygen saturation ratio increased by 75% with apparent sympathetic dysfunction, but never changed by > 25% in the other patients, and varied by < 15% in the volunteers. These results suggest that during tilt table testing, simultaneous assessment of brain and skeletal muscle oxygenation may provide a simple, objective aid for the identification of contributory sympathetic dysfunction.
Diagnostic Accuracy of KL‐6 as a Marker of Amiodarone‐Induced Pulmonary Toxicity
Authors: ENDOH YASUHIRO , HANAI RITSUKO , UTO KENTA , TANAKA TSUGURO , OHTA YOSHIMI , KASANUKI HIROSHI , OHNISHI SATOSHI
Published: October 2013

The diagnostic accuracy of KL‐6 as an indicator of amiodarone‐induced pulmonary toxicity was studied in 14 men (mean age =62 ± 12, range 33–76 years) treated with amiodarone. The indications for amiodarone were sustained ventricular tachycardia in 13 patients and atrial fibrillation in 1 patient with refractory heart failure. The KL‐6 cut‐off level was set at 520 U/mL. Group A consisted of two patients with amiodarone‐induced pulmonary toxicity, group B of five patients with other pulmonary disorders, and group C of seven patients without pulmonary disease. KL‐6 levels, percent diffusing capacity for carbon monoxide (%DLCO), and other laboratory markers were compared among these three groups. KL‐6 levels were significantly higher in group A than in group B and C (2550 ± 36, 252 ± 99, 198 ± 82 U/mL, respectively; P < 0.0001). KL‐6 levels in group B were below the cutoff value. %DLCO, C‐reactive protein (CRP), and lactic dehydrogenase (LDH) were abnormal in group A. The abnormal rates of CRP and LDH in group B were 80% and 40%, respectively. Of the seven patients with pulmonary disease, three patients (43%) could not undergo %DLCO testing because of poor physical condition. In one patient with amiodarone‐induced pulmonary toxicity, the KL‐6 level increased from 695 to 2,100 U/mL at a time of progression of interstitial changes. KL‐6 may be a useful marker of amiodarone‐induced pulmonary toxicity.