Atrial fibrosis in non-atrial fibrillation individuals and prediction of atrial fibrillation by use of late gadolinium enhancement magnetic resonance imaging.

INTRODUCTION: Besides the traditional concept of atrial fibrillation (AF) perpetuating atrial structural remodeling, there is increasing evidence that atrial fibrosis might precede AF, highlighting the need for better characterization of the fibrotic substrate. We aimed to assess atrial fibrosis by use of late gadolinium enhancement magnetic resonance imaging (LGE-MRI) in non-AF individuals and to identify predisposing risk factors. A second aim was to establish a risk score for the prevalence of AF using atrial fibrosis in addition to established clinical variables. METHODS AND RESULTS: Non-AF individuals without structural heart disease (n = 91) and matched AF controls (n = 91) underwent MRI for assessment of LGE. According to the established UTAH classification, atrial LGE ≥20% was considered extensive. Mean left atrial (LA) fibrosis in non-AF and AF individuals were 8.8 ± 6.5% and 12.5 ± 5.8%, respectively. Body mass index (BMI) >30 kg/m 2 and LA volume were predictors of atrial fibrosis. Diastolic function was not significantly different with respect to atrial fibrosis. A novel scoring system for the prevalence of AF (2 points for arterial hypertension and/or left ventricular ejection fraction <55%; 3 points for atrial fibrosis >6%) was derived demonstrating that patients in the intermediate/high-risk group had a significantly increased risk of AF. CONCLUSION: This study reports unexpectedly high atrial fibrosis in non-AF patients without apparent heart disease, highlighting the concept that structural fibrotic alterations may precede AF onset in a significant proportion of individuals. BMI as a predictor of atrial fibrosis suggests that lifestyle and drug intervention, that is, weight reduction, could positively influence fibrosis development. The derived risk score for AF prevalence provides the basis for prospective studies on AF incidence.

Healthcare Costs and Resource Utilization in Patients with Infantile Spasms Treated with H.P. Acthar Gel(®).

INTRODUCTION: The purpose of this study was to describe healthcare resource utilization and costs resulting from early (within 30 days of diagnosis) versus late (>30 days after diagnosis) treatment with prescriptions for H.P. Acthar(®) Gel (repository corticotropin injection; Acthar; Mallinckrodt) to manage infantile spasms (IS). METHODS: We included all patients in the Truven Health MarketScan(®) Commercial Claims and Encounters Database and the Truven Health MarketScan Multi-State Medicaid Database who were diagnosed with IS from 2007 to 2012. We performed unadjusted and adjusted regressions examining the relationship between healthcare resource utilization variables and their associated costs to compare outcomes in the early and late Acthar users. RESULTS: A total of 252 patients with IS who received Acthar fit our study criteria; 191 (76%) were early Acthar users. In adjusted analyses, we found that early Acthar use was associated with, on average, 3.8 fewer outpatient services (99% CI 0.7-6.7 fewer services). We did not find significant associations between early prescriptions for Acthar and number of hospitalizations, emergency room visits, prescription medications filled, or total costs of health services. CONCLUSION: Patients prescribed Acthar within 30 days of their IS diagnoses tended to have fewer outpatient services performed compared to patients prescribed Acthar later in the disease process. Although additional research is needed to confirm these exploratory findings, physicians may consider early treatment with Acthar to manage IS. FUNDING: This study was funded by a grant to the University of Washington from Mallinckrodt Pharmaceuticals.

Healthcare Costs and Resource Utilization in Patients with Multiple Sclerosis Relapses Treated with H.P. Acthar Gel(®).

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disorder with large annual costs. This study evaluated utilization and costs for the management of MS relapses with H.P. Acthar(®) Gel (repository corticotropin injection; Acthar; Mallinckrodt) compared to receipt of plasmapheresis (PMP) or intravenous immunoglobulin (IVIG) among patients with MS who experienced multiple relapses. METHODS: We identified patients with MS diagnoses who had relapses treated with intravenous methylprednisolone (IVMP), the first-line treatment for MS relapse. Patients who were treated for the subsequent relapses were eligible for the study. We analyzed 12- and 24-month healthcare utilization and costs among patients who received Acthar prescriptions compared to patients who were treated with PMP/IVIG using generalized linear and logistic regression models to calculate unadjusted and adjusted means and 95% confidence intervals. RESULTS: For the 12-month analysis, a total of 213 patients received Acthar prescriptions and 226 were treated with PMP or IVIG. Patients who received Acthar prescriptions were similar to those who received other treatments in terms of most demographic variables. Acthar recipients had fewer hospitalizations (0.2 vs. 0.4; P = 0.01) and received fewer outpatient services (29 vs. 43; P < 0.0001) but received more prescription medications (36 vs. 30; P < 0.0001) compared to recipients of PMP/IVIG. Patients who received Acthar prescriptions had lower inpatient and outpatient costs ($15,000 lower; P = 0.001; and $54,000 lower; P < 0.0001, respectively) but similar total costs. Similar results were seen in the cohort with 24 months of outcome data. CONCLUSION: Acthar may be a useful treatment option compared to PMP/IVIG for patients with MS experiencing multiple relapses. FUNDING: This study was funded by a grant to the University of Washington from Mallinckrodt Pharmaceuticals.

Variation in Outpatient Antibiotic Prescribing for Acute Respiratory Infections in the Veteran Population: A Cross-sectional Study.

BACKGROUND: Despite efforts to reduce antibiotic prescribing for acute respiratory infections (ARIs), information on factors that drive prescribing is limited. OBJECTIVE: To examine trends in antibiotic prescribing in the Veterans Affairs population over an 8-year period and to identify patient, provider, and setting sources of variation. DESIGN: Retrospective, cross-sectional study. SETTING: All emergency departments and primary and urgent care clinics in the Veterans Affairs health system. PARTICIPANTS: All patient visits between 2005 and 2012 with primary diagnoses of ARIs that typically had low proportions of bacterial infection. Patients with infections or comorbid conditions that indicated antibiotic use were excluded. MEASUREMENTS: Overall antibiotic prescription; macrolide prescription; and patient, provider, and setting characteristics extracted from the electronic health record. RESULTS: The proportion of 1 million visits with ARI diagnoses that resulted in antibiotic prescriptions increased from 67.5% in 2005 to 69.2% in 2012 (P < 0.001). The proportion of macrolide antibiotics prescribed increased from 36.8% to 47.0% (P < 0.001). Antibiotic prescribing was highest for sinusitis (adjusted proportion, 86%) and bronchitis (85%) and varied little according to fever, age, setting, or comorbid conditions. Substantial variation was identified in prescribing at the provider level: The 10% of providers who prescribed the most antibiotics did so during at least 95% of their ARI visits, and the 10% who prescribed the least did so during 40% or fewer of their ARI visits. LIMITATION: Some clinical data that may have influenced the prescribing decision were missing. CONCLUSION: Veterans with ARIs commonly receive antibiotics, regardless of patient, provider, or setting characteristics. Macrolide use has increased, and substantial variation was identified in antibiotic prescribing at the provider level. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Centers for Disease Control and Prevention.

Incidental LV LGE on CMR Imaging in Atrial Fibrillation Predicts Recurrence After Ablation Therapy.

OBJECTIVES: This study sought to evaluate the prognostic significance of left ventricular late gadolinium enhancement (LV-LGE) incidentally found in atrial fibrillation (AF) patients who undergo ablation therapy. BACKGROUND: LV-LGE provides prognostic information in patients with ischemic and nonischemic cardiomyopathies. However, data on the clinical significance of incidental LV-LGE in the AF population are limited. METHODS: A total of 778 patients who were referred for radiofrequency ablation of AF underwent cardiac magnetic resonance examinations between June 2006 and January 2013. Patients with a history of myocardial infarction or ablation therapy were excluded. The presence of LV-LGE was assessed by experienced imaging physicians. Patients were followed for arrhythmia recurrence after the radiofrequency ablation procedure. RESULTS: Of 598 patients included in the study, 60% were men with a mean age of 64 years and a median AF duration of 25 months. LV-LGE was detected in 39 patients (6.5%). There were 240 arrhythmia recurrences observed involving 40% of patients over a median follow-up period of 52 months. On univariate analysis, age (hazard ratio [HR]: 1.02; 95% confidence interval [CI]: 1.00 to 1.03), male sex (HR: 0.63; 95% CI: 0.47 to 0.86), diabetes (HR: 1.53; 95% CI: 1.03 to 2.27), CHADS2 score (HR: 1.19; 95% CI: 1.04 to 1.36), CHA2DS2-VASc score (HR: 1.18; 95% CI: 1.08 to 1.30), left atrial (LA) fibrosis (HR: 1.66; 95% CI: 1.41 to 1.96), LV-LGE (HR: 1.83; 95% CI: 1.11 to 3.03), persistent AF (HR: 1.52; 95% CI: 1.11 to 2.09), and LA area (HR: 1.03; 95% CI: 1.01 to 1.05) were significantly associated with arrhythmia recurrence. The recurrence rate was 69% in patients with LV-LGE compared with 38% in patients without LV-LGE (p < 0.001). In a multivariate model, LA fibrosis and LV-LGE were independent predictors of arrhythmia recurrence. CONCLUSIONS: In AF patients without history of myocardial infarction, LV-LGE is a significant independent predictor of arrhythmia recurrence after ablation therapy.

Does universal active MRSA surveillance influence anti-MRSA antibiotic use? A retrospective analysis of the treatment of patients admitted with suspicion of infection at Veterans Affairs Medical Centers between 2005 and 2010.

OBJECTIVES: After the implementation of an active surveillance programme for MRSA in US Veterans Affairs (VA) Medical Centers, there was an increase in vancomycin use. We investigated whether positive MRSA admission surveillance tests were associated with MRSA-positive clinical admission cultures and whether the availability of surveillance tests influenced prescribers' ability to match initial anti-MRSA antibiotic use with anticipated MRSA results from clinical admission cultures. METHODS: Analyses were based on barcode medication administration data, microbiology data and laboratory data from 129 hospitals between January 2005 and September 2010. Hospitalized patient admissions were included if clinical cultures were obtained and antibiotics started within 2 days of admission. Mixed-effects logistic regression was used to examine associations between positive MRSA admission cultures and (i) admission MRSA surveillance test results and (ii) initial anti-MRSA therapy. RESULTS: Among 569,815 included admissions, positive MRSA surveillance tests were strong predictors of MRSA-positive admission cultures (OR 8.5; 95% CI 8.2-8.8). The negative predictive value of MRSA surveillance tests was 97.6% (95% CI 97.5%-97.6%). The diagnostic OR between initial anti-MRSA antibiotics and MRSA-positive admission cultures was 3.2 (95% CI 3.1-3.4) for patients without surveillance tests and was not significantly different for admissions with surveillance tests. CONCLUSIONS: The availability of nasal MRSA surveillance tests in VA hospitals did not seem to improve the ability of prescribers to predict the necessity of initial anti-MRSA treatment despite the high negative predictive value of MRSA surveillance tests. Prospective trials are needed to establish the safety and effectiveness of using MRSA surveillance tests to guide antibiotic therapy.

Documentation of delirium in the VA electronic health record.

BACKGROUND: Delirium is a life-threatening, clinical syndrome common among the elderly and hospitalized patients. Delirium is under-recognized and misdiagnosed, complicating efforts to study the epidemiology and construct appropriate decision support to improve patient care. This study was primarily conducted to realize how providers documented confirmed cases of delirium in electronic health records as a preliminary step for using computerized methods to identify patients with delirium from electronic health records. METHODS: The Mental Health Consult (MHC) team reported cases of delirium to the study team during a 6-month study period (December 1, 2009 - May 31, 2010). A chart extraction tool was developed to abstract documentation of diagnosis, signs and symptoms and known risk factors of delirium. A nurse practitioner, and a clinical pharmacist independently reviewed clinical notes during each patients hospital stay to determine if delirium and or sign and symptoms of delirium were documented. RESULTS: The MHC team reported 25 cases of delirium. When excluding MHC team notes, delirium was documented for 5 of the 25 patients (one reported case in a physician's note, four in discharge summaries). Delirium was ICD-9 Coded for 7 of the 25 cases. Signs and symptoms associated with delirium were characterized in 8 physician notes, 11 discharge summaries, and 14 nursing notes, accounting for 16 of the 25 cases with identified delirium. CONCLUSIONS: Documentation of delirium is highly inconsistent even with a confirmed diagnosis. Hence, efforts to use existing data to precisely estimate the prevalence of delirium or to conduct epidemiological studies based on medical records will be challenging.

The degree of left atrial structural remodeling impacts left ventricular ejection fraction in patients with atrial fibrillation.

OBJECTIVES: The extent of left atrial (LA) wall structural remodeling (fibrosis) detected by late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) is correlated with advanced atrial fibrillation (AF). The concomitant occurrence of AF and left ventricular (LV) dysfunction is not uncommon. We studied the effect of LA fibrosis, a confounder of both AF and LV dysfunction, on LV ejection fraction (EF). STUDY DESIGN: For the analysis, we identified and included 384 patients from our retrospective AF database who underwent LGE-MRI and transthoracic echocardiography prior to AF ablation. Based on the degree of LA fibrosis, patients were categorized into four stages as: Utah 1 (<5% LA fibrosis), Utah 2 (5-20% fibrosis), Utah 3 (20-35% fibrosis), and Utah 4 (>35% fibrosis). RESULTS: The average pre-ablation LVEF was 60.5%±8.5% (n=24) in Utah stage 1 patients, 55.7%±10.3% (n=240) in Utah stage 2 patients, 51.7±11.5% (n=90) in Utah stage 3 patients, and 48.9%±11.6% (n=30) in Utah stage 4 patients (p<0.001, one-way ANOVA). The percentage of LA fibrosis was significantly negatively correlated to LVEF pre-ablation in a univariate analysis (p<0.001). In a multivariate model accounting for age, gender, AF type, and comorbidities such as diabetes and hypertension, Utah stage remained a significant predictor of pre-ablation EF (p<0.001). CONCLUSION: Patients with extensive LA fibrosis appear to have depressed LV function pre-ablation, suggesting that structural remodeling in the LA may also be triggering and promoting remodeling within the ventricular myocardium.

Atrial fibrillation ablation outcome is predicted by left atrial remodeling on MRI.

BACKGROUND: Although catheter ablation therapy for atrial fibrillation (AF) is becoming more common, results vary widely, and patient selection criteria remain poorly defined. We hypothesized that late gadolinium enhancement MRI (LGE-MRI) can identify left atrial (LA) wall structural remodeling (SRM) and stratify patients who are likely or not to benefit from ablation therapy. METHODS AND RESULTS: LGE-MRI was performed on 426 consecutive patients with AF without contraindications to MRI before undergoing their first ablation procedure and on 21 non-AF control subjects. Patients were categorized by SRM stage (I-IV) based on the percentage of LA wall enhancement for correlation with procedure outcomes. Histological validation of SRM was performed comparing LGE-MRI with surgical biopsy. A total of 386 patients (91%) with adequate LGE-MRI scans were included in the study. After ablation, 123 patients (31.9%) experienced recurrent atrial arrhythmias during the 1-year follow-up. Recurrent arrhythmias (failed ablations) occurred at higher SRM stages with 28 of 133 (21.0%) in stage I, 40 of 140 (29.3%) in stage II, 24 of 71 (33.8%) in stage III, and 30 of 42 (71.4%) in stage IV. In multivariate analysis, ablation outcome was best predicted by advanced SRM stage (hazard ratio, 4.89; P<0.0001) and diabetes mellitus (hazard ratio, 1.64; P=0.036), whereas increased LA volume and persistent AF were not significant predictors. LA wall enhancement was significantly greater in patients with AF versus non-AF controls (16.6±11.2% versus 3.1±1.9%; P<0.0001). Histological evidence of remodeling from surgical biopsy specimens correlated with SRM on LGE-MRI. CONCLUSIONS: Atrial SRM is identified on LGE-MRI, and extensive LGE (≥30% LA wall enhancement) predicts poor response to catheter ablation therapy for AF.

Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action.

Multiple sclerosis (MS) is a debilitating neurological disorder that affects nearly 2 million adults, mostly in the prime of their youth. An environmental trigger, such as a viral infection, is hypothesized to initiate the abnormal behavior of host immune cells: to attack and damage the myelin sheath surrounding the neurons of the central nervous system. While several other pathways and disease triggers are still being investigated, it is nonetheless clear that MS is a heterogeneous disease with multifactorial etiologies that works independently or synergistically to initiate the aberrant immune responses to myelin. Although there are still no definitive markers to diagnose the disease or to cure the disease per se, research on management of MS has improved many fold over the past decade. New disease-modifying therapeutics are poised to decrease immune inflammatory responses and consequently decelerate the progression of MS disease activity, reduce the exacerbations of MS symptoms, and stabilize the physical and mental status of individuals. In this review, we describe the mechanism of action, optimal dosing, drug administration, safety, and efficacy of the disease-modifying therapeutics that are currently approved for MS therapy. We also briefly touch upon the new drugs currently under investigation, and discuss the future of MS therapeutics.

Phylogeography of Aedes aegypti (yellow fever mosquito) in South Florida: mtDNA evidence for human-aided dispersal.

The invasive dengue vector Aedes aegypti has persisted for > 200 years in South Florida in the United States. We tested the hypotheses that Florida's landscape creates dispersal barriers and corridors and that long-distance human-aided dispersal structures populations of Ae. aegypti. We evaluated the phylogeography of 362 individuals from Florida's East and West Coasts with a 760-bp (418- and 342-bp fragments of ND5 and ND4, respectively) mitochondrial sequence. Populations from these two coasts were not significantly differentiated, suggesting that limited urbanization in central Florida is not a strong barrier to gene flow. Evidence for long-distance dispersal between Ft. Lauderdale and the West and Ft. Myers and the East indicates the importance of human-aided dispersal. West Coast populations showed no genetic differentiation, indicating that West Coast rivers and bays did not significantly impede gene flow. Phylogeographic analysis of haplotypes showed two distinct matrilines with no geographic patterns, suggesting multiple introductions or balancing selection.

Relationship between left atrial tissue structural remodelling detected using late gadolinium enhancement MRI and left ventricular hypertrophy in patients with atrial fibrillation.

AIMS: Therapeutic effectiveness of ablation of atrial fibrillation (AF) is related to cardiovascular comorbidities. We studied the relationship between left ventricular hypertrophy (LVH) and left atrial tissue structural remodelling (LA-SRM), in patients presenting for AF ablation. METHODS AND RESULTS: We identified 404 AF patients who received a late gadolinium enhancement magnetic resonance imaging (LGE-MRI) prior to catheter ablation. Left ventricular hypertrophy was defined as LV mass index >116 g/m(2) in men and >104 g/m(2) in women. One hundred and twenty-two patients were classified as the LVH group and 282 as the non-LVH group. We stratified patients into four stages based on their degree of LA-SRM (minimal, <5% fibrosis; mild, >5-20%; moderate, >20-35%; and extensive, >35%). All patients underwent catheter ablation with pulmonary vein isolation and posterior wall and septal debulking. The procedural outcome was monitored over a 1-year follow-up period. The mean LA-SRM was significantly higher in patients with LVH (19.4 ± 13.2%) than in non-LVH patients (15.3 ± 9.8%; P< 0.01). Patients with LVH generally had extensive LA-SRM (moderate and extensive stages; 38.5% of LVH group) as compared with non-LVH patients (23.1% of non-LVH group; P < 0.01). A Cox regression analysis showed that patients with LVH also had significantly higher AF recurrence rates than non-LVH patients (43.2 vs. 28%; P = 0.008) during the 1-year follow-up period post-ablation. CONCLUSION: Patients with LVH tend to have a significantly greater degree of LA-SRM, when compared with patients without LVH. Moreover, LA-SRM is a predictor for procedural success in patients undergoing AF ablation procedure.

Rapid ungated myocardial perfusion cardiovascular magnetic resonance: preliminary diagnostic accuracy.

BACKGROUND: Myocardial perfusion cardiovascular magnetic resonance (CMR) is a well-established method for detection of ischemic heart disease. However, ECG gating problems can result in image degradation and non-diagnostic scans, particularly in patients with arrhythmias. METHODS: A turboFLASH saturation recovery pulse sequence was used without any ECG triggering. One saturation pulse followed by 4-5 slices of undersampled radial k-space images was acquired rapidly, on the order of 40-50 msec per image. The acquisition of the set of 4-5 slices was continuously repeated approximately 4 times per second. An iterative constrained reconstruction method was used to reconstruct the ungated images. The ungated perfusion images were post-processed into three different sets of images (ungated, self-gated to near systole, and self-gated to near diastole). To test the ungated approach and compare the different processing methods, 8 patients scheduled for coronary angiography underwent stress and rest perfusion imaging with the ungated acquisition. Six patients had a history of atrial fibrillation (AF). Three blinded readers assessed image quality and presence/absence of disease. RESULTS: All 8 subjects successfully completed the perfusion CMR protocol and 7/8 underwent coronary angiography. Three patients were in atrial fibrillation during CMR. Overall, the CMR images were of high quality as assessed by the three readers. There was little difference in image quality between patients in AF compared to those in sinus rhythm (3.6±0.7 vs. 3.3±0.5). Stress/rest perfusion imaging showed normal perfusion in 4 patients, fixed perfusion defects in 2 patients, and reversible perfusion defects in 2 patients, corresponding with angiographic results. Pooled results from the independent readers gave a sensitivity of 0.92 (CI 0.65-0.99) and specificity of 0.92 (CI 0.65-0.99) for the detection of coronary artery disease using ungated perfusion imaging. The same sensitivity, and a specificity of 1 (CI 0.76-1), was achieved when the images were self-gated after acquisition into near systole or near diastole. CONCLUSIONS: Ungated radial dynamic perfusion CMR can give high quality imaging in patients in sinus rhythm and during atrial fibrillation. In this small cohort, high diagnostic accuracy was possible with this rapid perfusion imaging sequence. An ungated approach simplifies the acquisition and could expand the role of perfusion CMR to include patients with arrhythmia and those with gating problems.

Higher degree of left atrial structural remodeling in patients with atrial fibrillation and left ventricular systolic dysfunction.

BACKGROUND: Catheter ablation significantly improves the left ventricular (LV) function in patients with atrial fibrillation (AF) and LV systolic dysfunction. In this study, we compared the degree of left atrial structural remodeling (LA-SRM) in patients with normal versus reduced LV ejection fraction (LVEF). We also studied the impact of LA-SRM on LVEF improvement in patients undergoing ablation of AF. METHOD AND RESULTS: We categorized 384 patients into 2 groups based on their cardiac function: reduced LVEF group (LVEF ≤50%; n = 105) and normal LVEF group (LVEF > 50%; n = 279). LVEF was determined prior and mean 8 ± 3 months after catheter ablation for AF. Percentage of LA-SRM was quantified using LGE-MRI and patients were classified into 4 groups based on the amount of structural remodeling in their LA wall: minimal ≤ 5%, mild = 5-20%, moderate = 20-35%, and extensive ≥ 35%. The average preablation LA-SRM (21.5 ± 13.2% vs 15.4 ± 10.0%; P < 0.001) was significantly higher in reduced LVEF group than normal LVEF group. Among the 105 patients with reduced LVEF, while there was a modest 11.7 ± 8.4% average increase in LVEF following ablation, the greatest increase was seen in patients with less extensive LA-SRM (minimal = 19.3 ± 5.1%, n = 3, P = 0.02 and mild = 16.6 ± 9.9%, n = 48, P < 0.001). Patients with moderate and extensive fibrosis had an average EF improvement of 8.7 ± 11.1% and 2.8 ± 6.4%, respectively (n = 39, P < 0.001 and n = 15, P = 0.11, respectively). CONCLUSION: Patients with LV systolic dysfunction displayed a comparatively greater LA-SRM than patients with normal LVEF. Patients with lesser LA-SRM experienced a greater improvement in LVEF after catheter ablation for AF.

The effect of fat pad modification during ablation of atrial fibrillation: late gadolinium enhancement MRI analysis.

BACKGROUND: Magnetic resonance imaging (MRI) can visualize locations of both the ablation scar on the left atrium (LA) after atrial fibrillation (AF) ablation and epicardial fat pads (FPs) containing ganglionated plexi (GP). METHODS: We investigated 60 patients who underwent pulmonary vein antrum (PVA) isolation along with LA posterior wall and septal debulking for AF. FPs around the LA surface in well-known GP areas (which were considered as the substitution of GP areas around the LA) were segmented from the dark-blood MRI. Then the FP and the ablation scar image visualized by late gadolinium enhancement (LGE)-MRI on the LA were merged together. Overlapping areas of FP and the ablation scar image were considered as the ablated FP areas containing GP. Patients underwent 24-hour Holter monitoring after ablation for the analysis of heart rate variability. RESULTS: Ablated FP area was significantly wider in patients without AF recurrence than those in patients with recurrence (5.6 ± 3.1 cm(2) vs 4.2 ± 2.7 cm(2) , P = 0.03). The mean values of both percentage of differences greater than 50 ms in the RR intervals (pRR > 50) and standard deviation of RR intervals over the entire analyzed period (SDNN), which were obtained from 24-hour Holter monitoring 1-day post-AF ablation, were significantly lower in patients without recurrence than those in patients with recurrence (5.8 ± 6.0% vs 14.0 ± 10.1%; P = 0.0005, 78.7 ± 32.4 ms vs 109.2 ± 43.5 ms; P = 0.005). There was a significant negative correlation between SDNN and the percentage of ablated FP area (Y = -1.3168X + 118.96, R(2) = 0.1576, P = 0.003). CONCLUSION: Extensively ablating LA covering GP areas along with PVA isolation enhanced the denervation of autonomic nerve system and seemed to improve procedural outcome in patients with AF.

Distributions of Competing Container Mosquitoes Depend on Detritus Types, Nutrient Ratios, and Food Availability.

Coexistence of competitors may result if resources are sufficiently abundant to render competition unimportant, or if species differ in resource requirements. Detritus type has been shown to affect interspecific competitive outcomes between Aedes albopictus (Skuse) and Aedes aegypti (L.) larvae under controlled conditions. We assessed the relationships among spatial distributions of detritus types, nutrients, and aquatic larvae of these species in nature. We collected mosquitoes, water, and detritus from artificial containers across 24 Florida cemeteries that varied in relative abundances of Ae. aegypti and Ae. albopictus.We measured nutrient content of fine particulate organic matter in water samples as total N, P, and C and ratios of these nutrients. We quantified food availability via a bioassay, raising individual Aedes larvae in the laboratory in standard volumes of field-collected, particulate-containing water from each cemetery. Quantities of detritus types collected in standard containers were significant predictors of nutrients and nutrient ratios. Nutrient abundances were significant predictors of relative abundance of Ae. aegypti, and of larval survival and development by both species in the bioassay. Survival and development of larvae reared in particulate-containing water from sites decreased with decreasing relative abundance of Ae. aegypti. These data suggest that N, P, and C availabilities are determined by detritus inputs to containers and that these nutrients in turn determine the feeding environment encountered by larvae, the intensity of interspecific competition among larvae, and subsequent relative abundances of species at sites. Detritus inputs, nutrients, and food availability thus seem to contribute to distributions of Ae. aegypti and Ae. albopictus in cemetery containers throughout Florida.

Do natural container habitats impede invader dominance? Predator-mediated coexistence of invasive and native container-dwelling mosquitoes.

Predator-mediated coexistence of competitors occurs when a species that is superior in competition is also more vulnerable to a shared predator compared to a poorer competitor. The invasive mosquito Aedes albopictus is usually competitively superior to Ochlerotatus triseriatus. Among second instar larvae, A. albopictus show a lesser degree of behavioral modification in response to water-borne cues from predation by the larval midge Corethrella appendiculata than do O. triseriatus, rendering A. albopictus more vulnerable to predation by C. appendiculata than O. triseriatus. The hypothesis that C. appendiculata predation favors coexistence of these competitors predicts that C. appendiculata abundances will be negatively and positively correlated with A. albopictus and O. triseriatus abundances, respectively, and that coexistence will occur where C. appendiculata are common. Actual abundances of O. triseriatus, A. albopictus, and C. appendiculata in three habitats fit this prediction. In natural container habitats like tree holes, C. appendiculata were abundant and competitors co-existed at similar densities. In cemeteries and tires, which occur primarily in non-forested, human-dominated habitats, A. albopictus dominated, with abundances twice those found in tree holes, but C. appendiculata and O. triseriatus were rare or absent. We also tested for whether antipredatory behavioral responses of A. albopictus differed among habitats or populations, or were correlated with local C. appendiculata abundances. We could detect no differences in A. albopictus antipredatory behavioral responses to water-borne cues from predation. Tree hole habitats appear to promote co-existence of O. triseriatus and A. albopictus through interactions with predatory C. appendiculata, and this predator effect appears to limit invasion success of A. albopictus in tree holes. There are many studies on predator-mediated coexistence in natural habitats but to our knowledge this is the first study to suggest differential predator-mediated coexistence between natural and man-made habitats.

Threat-Sensitive Behavioral Responses to Concentrations of Water-Borne Cues from Predation.

Aquatic organisms often detect predators via water-borne chemical cues, and respond by showing reduced activity. Prey responses may be correlated with the concentration of predation cues, which would result in graded antipredator behavioral responses that adjust potentially costly behavioral changes to levels that are commensurate with the risk of predation. Larvae of the predatory mosquito Toxorhynchites rutilus prey upon other container-dwelling insects, including larvae of the mosquito Ochlerotatus triseriatus. Previous work has established that O. triseriatus reduce movement, foraging, and time below the surface, and increase the frequency of resting at the surface, in the presence of water-borne cues from predation by T. rutilus. We tested whether these responses by O. triseriatus are threat sensitive by recording behavior of fourth instar larvae in two runs of an experiment in which we created a series of concentrations (100, 10, 1, 0.1, and 0.01% and 100, 70, 40, 20, and 10%) of water that had held either O. triseriatus larvae alone (control) or a T. rutilus larva feeding on O. triseriatus (predation). We also tested whether associated effects on time spent feeding are threat sensitive by determining whether frequencies of filtering or browsing are also related to concentration of cues. The frequencies of resting and surface declined, whereas frequency of filtering (but not browsing) increased more rapidly with a decrease in concentration of predation cues compared with control cues. Thus, O. triseriatus shows a threat sensitive behavioral response to water-borne cues from this predator, adjusting its degree of behavioral response to the apparent risk of predation.