AF Group Research Articles

Plasma oxidative stress and inflammatory biomarkers are associated with the sizes of the left atrium and pulmonary vein in atrial fibrillation patients.

Oxidative stress and inflammatory processes are responsible for the pathogenesis of AF, but their relationship with the sizes of the LA and PVs in AF patients remains unclear. Oxidative stress and inflammatory processes are associated with the sizes of the LA and PVs in AF patients. 82 AF patients were compared to 30 control patients by using a case-control study design. Oxidative stress, inflammatory biomarkers and the sizes of the LA and PVs were detected. (1) Hs-CRP, IL-6, IL-8, TNF-α, MDA and ox-LDL were higher, and SOD was lower in AF patients than in control patients. Hs-CRP, MDA and ox-LDL were higher in permanent AF patients than in paroxysmal and persistent AF patients. (2) CsA of LSPV, RSPV, RIPV, LAA and LAV were statistically higher in AF patients than in control patients. CsA of RSPV, LSPV, LIPV and LAV were higher in permanent AF patients than in paroxysmal and persistent AF patients. (3) In the AF group, hs-CRP and TNF-α were positively correlated with LAV; MDA was positively correlated with CsA of LAA, LSPV and LAV; SOD was passively correlated with CsA of LAA and LAV; ox-LDL was positively correlated with CsA of LAA and LAV. Multivariate logistic regression analysis showed hs-CRP, ox-LDL, RSPV CsA, LIPV CsA and LAV were associated with AF. Oxidative stress, inflammatory biomarkers and the sizes of the LA and PVs were significantly increased in AF patients. Hs-CRP, ox-LDL, RSPV CsA, LIPV CsA and LAV were associated with AF persistence.

The significance of the left atrial volume index in prediction of atrial fibrillation recurrence after electrical cardioversion.

Introduction: Electrical cardioversion (ECV) is a safe method for the treatment of atrial fibrillation. It seems that left atrial volume index (LAVI) could be a good marker in predicting the success of ECV. The purpose of this study is to assess of the significance of LAVI measurement before ECV in predicting the recurrence of the AF. Methods: Fifty-one patients with AF, selected for ECV were studied in the cardiology department of Tabriz University of medical sciences. The clinical and demographic data of all the patients were obtained. Echocardiography was performed before and also three months after ECV. Patients were separated into two groups: those who maintained SR and those with relapse of AF diagnosed by clinical manifestations and electrocardiography (ECG). Results: Sinus rhythm (SR) was maintained in 76.5 percent of the patients following the three months after ECV. The age, sex and the body mass index (BMI) were not significantly different between SR and AF groups. Two groups showed no significant differences considering pre-ECV medical history including medications and systemic diseases. The initial LAVI of SR group was 42.21±12.4 mL/m2 and AF group was 96.08±52.21 mL/m2, the initial LAVI was significantly different between two groups (P = 0.000). The LAVI of SR group decreased significantly (5.69±0.74 mL/m2) after three months, LAVI decreased from 42.21 ± 12.4 ml/m2 to 37.51 ± 10.52 mL/m2. (P = 0.000). The cut-off point of LAVI value in predicting the maintenance of SR was 55 mL/m2. Conclusion: The present study indicates that LAVI is a powerful forecaster of the recurrence of AF after ECV. The LAVI measurement could be a useful method in the selection of the patients with AF for ECV.

High Density Mapping of Atrial Fibrillation: Regional Atrial Substrate Abnormalities and Implications for Substrate Ablation

Background: It is well-known that there are progressive changes in AF. However, the use of high density mapping to demonstrate atrial remodelling has not been reported. Objective: We sought to evaluate the utility of high density electroanatomic mapping to demonstrate progressive substrate in patients with paroxysmal and persistent AF. Methods: 33 consecutive patients with AF underwent high-density electroanatomic maps of the LA prior to PVI. The LA was divided into 5 segments for regional analysis of mean bipolar voltage. The Confidense® algorithm was used to collect EGMs from a multipolar Lasso® catheter during distal CS pacing at 600msec (Biosense Webster). Patients with structural heart disease were excluded and comorbidities were evenly matched across both groups. Results: 15 paroxysmal AF and 18 persistent AF patients were studied. Mean age was similar (58.4 ± 10 vs 58.1 ± 7years) and 26 (78%) were male. A mean total of 1600 ± 770 and 1483 ± 773 points were collected in each group. The global mean LA voltage was significantly lower in the persistent AF group (2.05 ± 0.6 vs 1.46 ± 0.4 mV, p < 0.001) and consistent across all 5 segments (Figure). The posterior segment demonstrated the greatest difference in regional voltage between groups (2.13 ± 0.9 vs 1.34 ± 0.5 mV, p < 0.002). Conclusion: High density atrial mapping demonstrates regional LA substrate abnormalities in persistent AF not present in paroxysmal AF. These regions may represent targets for substrate modification in persistent AF

Evaluation of intra- and interatrial synchronization in patients with paroxysmal atrial fibrillation by dual gate Doppler

Objective To evaluate intra- and interatrial synchronization in patients with paroxysmal atrial fibrillation (PAF) by dual gate Doppler and discuss the predictive value of atrial asynchrony for detecting PAF. Methods Twenty-nine patients with PAF as AF group and 24 healthy volunteers as control group underwent echocardiography. The time interval of the onset of a′ wave between mitral annular septal and lateral site was T1 by dual gate Doppler, which was used to evaluate left atrial synchronization. The time intervals from the onset of a′ wave at tricuspid annular right ventricular free wall site to a′ wave at tricuspid annular septal site and mitral annular lateral site were T2 and T3, which were respectively used to evaluate right atrial and interatrial synchronization. The greater time interval predicted the worse synchronization. Compared these indexes between two groups, the most valuable index was obtained and combined with left atrial volume index (LAVI) to predict PAF, its optimal values were found out by ROC curve. Results ①There were no significant differences in many other basic indexes between two groups (P>0.05). However, compared with control group, the ratio of early diastolic transmitral flow velocity (E) and mitral annular velocity of septal site (e′), the diameters and volume indexes of atria were significantly increased in AF group. ②T1, T2 and T3 (standardized before and after) increased significantly in AF group (P<0.01). Standardized T1 had the largest area under curve (AUC) for detecting PAF. The AUC of standardized T1 and LAVI were 76.6% and 84.1%. Standardized T1≥29.55 ms and LAVI≥21.60 ml/m2 were combined for detecting PAF (sensitivity 82.8%, specificity 79.2%, AUC 87.1%). ③Standardized T1 was positively correlated with age, left atrial systolic diameter, LAVI, RAVI and E/e′ (P<0.05). Conclusions Patients with PAF have worse intra- and interatrial synchronization and left atrial asynchrony can provide predictive value for detecting PAF. Dual gate Doppler is expected to be a new technique for evaluating intra- and interatrial synchronization accurately and detecting the risk of AF. Key words: Echocardiography; Atrial fibrillation; Atrial function; Dual Gate Doppler

Effects of Long-Term Exposure to an Electronic Containment System on the Behaviour and Welfare of Domestic Cats.

Free-roaming cats are exposed to a variety of risks, including involvement in road traffic accidents. One way of mitigating these risks is to contain cats, for example using an electronic boundary fence system that delivers an electric ‘correction’ via a collar if a cat ignores a warning cue and attempts to cross the boundary. However, concerns have been expressed over the welfare impact of such systems. Our aim was to determine if long-term exposure to an electronic containment system was associated with reduced cat welfare. We compared 46 owned domestic cats: 23 cats that had been contained by an electronic containment system for more than 12 months (AF group); and 23 cats with no containment system that were able to roam more widely (C group). We assessed the cats’ behavioural responses and welfare via four behavioural tests (unfamiliar person test; novel object test; sudden noise test; cognitive bias test) and an owner questionnaire. In the unfamiliar person test, C group lip-licked more than the AF group, whilst the AF group looked at, explored and interacted more with the unfamiliar person than C group. In the novel object test, the AF group looked at and explored the object more than C group. No significant differences were found between AF and C groups for the sudden noise or cognitive bias tests. Regarding the questionnaire, C group owners thought their cats showed more irritable behaviour and AF owners thought that their cats toileted inappropriately more often than C owners. Overall, AF cats were less neophobic than C cats and there was no evidence of significant differences between the populations in general affective state. These findings indicate that an electronic boundary fence with clear pre-warning cues does not impair the long term quality of life of cats.

Regional quantification of left atrial early diastolic strain in two groups of patients with mitral stenosis: normal sinus rhythm vs atrial fibrillation.

Strain rate imaging (SRI) is proposed for assessing atrial function. There are limited studies on the role of SRI in assessing the left atrial (LA) function in patients with mitral stenosis (MS). We decided to assess LA early diastolic strain to evaluate LA conduit function in two groups of patients with MS. A total of 49 patients with moderate to severe MS, scheduled for percutaneous transluminal mitral commissurotomy, were categorized into two groups: normal sinus rhythm (NSR, n=24) and persistent atrial fibrillation (AF, n=25). Early diastolic strain was measured via SRI in four mid-left atrial walls by transthoracic echocardiography. Left atrial volume was significantly higher in AF group. LA early diastolic strain was significantly reduced in AF patients in three walls: interatrial septum (-6.78±6.22% vs -11.44±6.35%, P=.016), anterior wall (-4.47±4.30% vs -12.52±10.62%, P=.002), and inferior wall (-2.87±3.23% vs -9.73±9.67%, P=.003). After adjustment for age, heart rate, LA volume, LA thrombus, and LAA emptying velocity, there was a significant correlation between the presence of AF and left atrial average early diastolic strain. This correlation was also remarkable between existence of AF and two LA walls (i.e., anterior and inferior walls of the LA). There was reduced average early diastolic strain in the presence of AF compared to NSR in MS patients regardless of LA volume and age. In AF patients, there is not only a loss of atrial late diastolic contraction, but also there is a reduction in early diastolic shortening of LA myocardium.

Reduction of c-kit positive cardiac stem cells in patients with atrial fibrillation

BackgroundWe aimed to determine expression patterns of cardiac stem cells in the left atrium (LA) tissue from patients with atrial fibrillation. MethodsLA appendages were obtained during open-heart surgery and processed for explant cell culture and tissue analysis (n=319). The total number of grown cells and c-kit positive cells were analyzed by flow cytometry after 4 weeks of culture. The remaining tissue was used for Masson's trichrome staining to determine the area of the fibrosis. ResultsThe diameter of the LA, as measured by echocardiography, was significantly larger in the AF group than in the sinus rhythm group. Reverse transcription polymerase chain reaction analysis revealed higher expression of collagen in the AF group and an increase in the expression of basic fibrosis growth factor and transforming growth factor-2 and -3. Masson's trichrome staining showed progression of fibrosis in the AF tissue. In addition, the expression of apoptosis-related genes were significantly higher in AF group. There was no difference in the expression of connexin-40 between groups, while the expression of connexin-43 was decreased and that of connexin-45 was increased in the AF group. The total numbers of grown cells as well as c-kit positive cells after 4 weeks of cardiac tissue culture were significantly lower in the AF group. ConclusionProgression of remodeling in LA tissue was observed in AF patients. The number of c-kit positive cells cultured from LA appendages was reduced in AF patients, suggesting impairments in self-renewal.

Abstract 3487: Alcohol programs the pituitary to produce aggressive prolactin-producing tumors

Abstract Chronic alcohol consumption is known to increase prolactin levels in blood and cell proliferation in pituitary prolactin-producing cells known as lactotropes, resulting in hyperprolactinemia in human and animals. We have recently shown that alcohol abuse during pregnancy result in fetal programming that alters lactotropic cell production of prolactin in the offspring during the adulthood. We determined whether fetal alcohol exposure increases the susceptibility to estrogen-induced pituitary prolactin-secreting tumors (prolactinomas). Pregnant Fischer 344 rats were fed between gestational days 7 and 21 with a liquid diet containing alcohol (AF), pair-fed with isocaloric liquid diet (PF), or fed ad libitum with rat chow (AD). At 90 days of age, female offspring rats were ovariectomized and received a subcutaneous estradiol implant. These rats were sacrificed at 3 moths after the estradiol implants. At the time of sacrifice, pituitaries of these animals were inspected for tumor and whole body were inspected for any tumor metastasis. Estradiol treatment increased pituitary weight about 5-folds in AD and PF treated groups and increased about 30-folds in the AF treated group. Most tumors in the AF group were hemorrhagic. About 30% AF rats had some tumors in the non-pituitary sites. AD and PF rats did not show any non-pituitary site tumor. Histopathological evaluation revealed that tumors in AF group were more densely packed cells as compare to the PF and AD groups who showed uniform cells with abundant cytoplasm. Pituitary tumor from AF animals showed strong nuclear p53, Ki67 and prolactin immunoreactivity. When AF rat pituitaries were grown in cultures, cells rapidly grew and formed colonies. Colony formation and rapid growth rate were not observed in cells of the pituitary from PF and AD rats. When pituitary tumor cells of AF-treated pituitary, but not AD- or PF-treated pituitaries were grown in ultra-low attachment plate, spheres developed. These spheres expressed genes and proteins related to multipotency (OCT4, NANOG, KLF4, SOX2, Nestin, CD34 and CD133). Differentiated cells from pituitary tumorspheres of AF animals successfully induce tumor in scid mice after three weeks from cells transplantation. In addition, pituitary tumor from AF animals showed strong immunoreactivity for N-cadherin and Snail, two epithelial-mesenchymal transitions (EMT) factors. Furthermore, RNA-seq of genes in tumor pituitaries of AF and AD rats revealed 8782 genes are significantly changed in AF compared to AD P&amp;lt;0.01. Many of these genes were involved in the cell migration, actin cytoskeletal regulation and cell-cell junction formations which are the most important phenotypes occur during EMT. These data provide evidence for the possible development of aggressive prolactinoma development in the pituitary after estrogen treatment in fetal alcohol exposed female rats. (This work is supported by a National Institute of Health grant R01 AA11591). Citation Format: Shaima Jabbar, Jinhee Park, William Belden, Dipak K. Sarkar. Alcohol programs the pituitary to produce aggressive prolactin-producing tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3487.

Environmental remediation potential of Perinereis aibuhitensis (Polychaeta) based on the effects of temperature and feed types on its carbon and nitrogen budgets

ABSTRACTThe effects of three temperatures (15°C, 20°C and 25°C) and four feed types (artificial feed, AF; sediment, SM; fish faeces, FF; and fish meat, FM) on the growth, carbon budget and nitrogen budget of the polychaete Perinereis aibuhitensis were evaluated over a 35 day period. The final body weight and specific growth rate (SGR) of P. aibuhitensis were significantly affected by temperature and feed types (T, F = 15.831, P = 0.000; Feed, F = 81.827, P = 0.000), but the interaction between these factors was not significant (F = 0.435, P = 0.848). The worms achieved the highest SGR in the AF group at 20°C. However, the SGR in the SM group was only half that of the other groups. The food conversion efficiency (FCE) was significantly lower at 25°C than at 15°C and 20°C (P < 0.05). The FCE was highest in the FM group (P = 0.000), with a mean of 39.83%. The apparent digestibility rate (ADR) at 25°C was significantly higher than at 15°C and 20°C (P < 0.05). These findings suggest that the higher FCE coupled with ADR (78.48%) resulted in higher SGR in worms that were fed artificial feed at 20°C. The slow growth in the SM group was attributed to the lower organic content in sediment and the higher expenditure of carbon and nitrogen in faeces and metabolism. The proportion of total C and N deposited was lower in groups fed with the higher-quality feed used for fish cage farming. Most of feed carbon and nitrogen were released into the water by polychaetes, which was good for the sediment environment recovery under the fish cages.

Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation: A meta-analysis and systematic review of randomized controlled trials.

Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive.A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed.A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction.This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation.

Echocardiographic measures of atrial function may predict atrial fibrillation in stroke patients

Objective: In patients with a prior stroke or transient ischemic attack (TIA) and atrial fibrillation anticoagulant treatment is indicated. This study’s purpose was to investigate if echocardiography can predict unknown AF in patients after stroke.Design: Prospectively, 174 stroke/TIA patients without diagnosed AF underwent echocardiographic evaluation including tissue Doppler imaging (TDI) focusing on functional parameters of the left atrium and left ventricular diastolic function. AF screening was performed during 30 d.Results: Fifteen patients (8.6%) were diagnosed with AF. Echocardiography in the AF group compared to those without AF, showed larger left atrial volume index (LAVI), (37.2 ± 6.7 vs. 31.6 ± 8.6 ml/m2, p = 0.018), lower A’ velocities in ventricular (5.9 ± 2.2 vs. 7.2 ± 1.6, p = 0.010) and atrial (4.8 ± 1.4 vs. 5.9 ± 1.4, p = 0.013) septa, higher LAVI/A’ in ventricular septum (6.7 (5.0–8.7) vs. 4.2 (3.2–5.5), p = 0.001) and atrial septum (8.5 (5.9–11.0) vs. 5.1 (4.1–6.8), p = 0.003). Receiver operating characteristic analyses to detect AF was performed, area under the curve for LAVI was 0.71 (0.61–0.83), p = 0.008, and for LAVI/A’ in ventricular septum 0.76 (0.59–0.93), p = 0.006 and atrial septum 0.78 (0.63–0.93), p = 0.002, respectively.Conclusions: LAVI and measures of atrial contraction as measured by TDI predict unknown AF in patients after an stroke/TIA and may be used to detect silent AF.

Active and Passive Application of the Phosphoric Acid on the Bond Strength of Lithium Disilicate.

The objective of this study was to evaluate the effect of passive or active phosphoric acid (PA) application after hydrofluoric acid (HA) treatment on the microshear bond strength of lithium disilicate. Thirty ceramic discs were made with IPS Emax 2 (10 mm thick and 10 mm diameter). The specimens were divided into 3 groups, A: 9.6% HA application; AF: 9.6% HA application + cleaning with 37% PA in passive mode and AFF: 9.6% HA application + cleaning with 37% PA in active mode. For the microshear test, four tygons (0.9 mm diameter and 0.2 mm high) were filled with resin cement (RelyX Ultimate) and placed on the ceramic disks. After testing, the fracture modes were examined under scanning electron microscopy. Data were analyzed by one-way ANOVA and Tukey's post test (α=0.05). The bond strength values were significantly higher in Group AFF (11.0±2.5 MPa) compared with group A (8.1±2.6 MPa) (p<0.002). AF group was not statistically different (9.4±2.5 MPa) from Group A. It was concluded that the active application of 37% PA after 9.6% HA increases the microshear bond strength values between the resin cement and lithium disilicate ceramic.

"Immunonutrition" Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents.

BackgroundImmunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats.DesignRats were fed with enteral Peptamen® HN (HN group), Peptamen® AF containing n-3 PUFAs (AF group) or Peptamen® AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed.ResultsCompared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05) and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats.ConclusionsAlthough n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore, mortality was higher after L-arginine supplementation.

Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up

Background and purposeHealth related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. Material and methods750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1–2, N0 glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2Gy/day, 5days/week in 49days, total dose 68Gy) or accelerated fractionation (1.1+2.0Gy/day, 5days/week in 35days, total dose 68Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6months and 1, 2 and 5years after start of treatment. ResultsThe AF group reported HRQoL was significantly lower at eRT and at 3months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6months and 5years. Scores related to functional oral intake never reached baseline. ConclusionIn comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.

The Correlation between Left Atrial Deformation Indices and the CHA2DS2 - VASc Risk Score in Patients with Atrial Fibrillation

Objectives: To assess the relation between left atrial systolic strain and CHA2DS2 -VASc score in patients with non valvular atrial fibrillation and to assess whether it can be used in guiding the decision for oral anticoagulation. Methods: The study included 100 patients with non- valvular persistent AF (group I) compared to 100 individuals with sinus rhythm of matching age and gender (group II). Standard two-dimensional echocardiography, PW Doppler and TDI derived velocity and strains were used to assess LA function then its correlation with CHA2DS2-VASc score in group I was evaluated. Results: The prevalence of DM (P<0.001), HTN (P=0.001), prior stroke (P<0.001), heart failure (P < 0.001) and peripheral vascular disease (P < 0.001) was increased in patients in group I. Group I showed significant increase in LA diameters (anterio-posterior, transverse and longitudinal) P E‚ 0.001, LA volumes (maximal and minimal P < 0.001 and mitral E/e ratio P E‚ 0.05. The correlation between LA emptying fraction and CHA2DS2 - VASc score was negative and significant (P < 0.05). Systolic LA strain was significantly reduced in patients with AF (P < 0.001) and it was negatively correlated to CHA2DS2 - VASc score but without statistical significance. There was no significant difference of LA systolic strain between the CHA2DS2 - VASc score of < 2 points and ≥ 2 points (P = 0.52). Systolic LA strain ≤ 17.44 was shown to have the best diagnostic accuracy (sensitivity = 42.11 %; specificity = 62.07%) in predicting CHA2DS2 - VASc ≥ 2. Conclusion: LA systolic strain is significantly reduced in AF patients and negatively correlated to CHA2DS2- VASc score and no significant difference between LA systolic strain in patients with CHA2DS2 - VASc score of < 2 points and ≥ 2 points so LA strain may be a tool that helps in guiding the decision for oral anticoagulation.

Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats1–3

Background: Zinc deficiency has been well documented in alcoholic liver disease.Objective: This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-induced gut leakiness and endotoxemia.Methods: Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) Lieber-DeCarli liquid diet for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00–5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed with the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot analysis.Results: The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin concentrations of the AF rats were 136% greater than those of the PF rats, whereas the AF/Zn rats did not differ from the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group had reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group had upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with those of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group.Conclusions: The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats.

Abstract 14355: Sinus Rhythm Prior to Catheter Ablation Positively Impacts Ablation Outcome in Non-Paroxysmal Atrial Fibrillation Patients

Background: Catheter ablation of non-paroxysmal atrial fibrillation (NPAF) is associated with longer procedure times and lower long-term success rates than that of paroxysmal AF. We tested the hypothesis that NPAF patients entering the EP laboratory (lab) with sinus rhythm (SR) have shorter procedure time and better ablation-outcome than those with AF as the entry-rhythm. Methods: Total of 804 consecutive NPAF patients undergoing radiofrequency catheter ablation at our center were included in this prospective analysis. Based on the presenting rhythm in the EP lab, patients were classified into two groups; patients on SR (group 1, n=236, age 63±10 years, male 71%, LVEF 55.2±8.4, LA size 4.5±0.9 cm), patients in AF (group 2, n=568, age 64±10 years, male 69%, LVEF 54.4±11.4, LA size 4.6±0.6 cm). All patients were followed up for 38±6 months for arrhythmia recurrence by event recorder, ECG and Holter monitoring. Results: The baseline characteristics were not different between the groups. When comparing the procedural parameters between the groups, patients presenting with SR required significantly shorter radiofrequency time (64.1±30.7 min vs. 82.3±29.4 min in AF group, p&lt;0.0001) and procedure times (143.9±91.2 min vs. 162.3±62.2 min in AF group, p=0.019). At the end of follow-up, significantly higher recurrence rate was noted in those presenting with AF compared to patients on SR at the procedure; 264 of 568 (47%) vs. 80 of 236 (34%) respectively, log-rank p=0.002 (unadjusted hazard ratio 1.55 [1.17 - 2.05]) (figure). After adjusting for AF type, age, gender, LA size, and LVEF in multivariable Cox model, patients presenting with AF at procedure were twice more likely to fail compared to those on SR (hazard ratio 1.91 (95% CI 1.19 to 4.15), p=0.001). Conclusion: Sinus rhythm prior to catheter ablation for non-paroxysmal AF decreases the duration of ablation and increases the long-term efficacy of the procedure. Figure: Kaplan-Meier curve showing recurrence by study groups

Abstract 14766: Pulmonary Vein Isolation Alone is Not Superior to Amiodarone for the Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Randomized Trial

Introduction: The best treatment option for the management of patients (pts) with heart failure (HF) and persistent AF is unknown. The AATAC trial showed that catheter ablation (CA) is superior to Amiodarone in achieving freedom from AF at follow up. In this analysis we present the outcome sorted by type of AF procedure. Methods: AATAC was a randomized multicenter study. Pts with persistent AF, dual chamber ICD or CRTD, NYHA II-III and LV EF &lt;40% within the last 6 months were randomly assigned (1:1 ratio) to undergo CA for AF (group 1=102 pts) or receive AMIO, (group 2=101 pts). Recurrence of AF was the primary end point. Based on operator’s choice patients could undergo pulmonary vein isolation alone (PVI) or PVI plus posterior wall plus non PV trigger ablation (PVI+PW+NPV) as detected by high dosage of isoproterenol. Results: PVI was performed in 22 patients undergoing ablation, while PVI+PW+NPV ablation was performed in 80 patients. Baseline characteristics were not different between the groups. At 26±8 months follow-up, the success rates in PVI, PVI+PW+NPV, and AMIO groups were 8 [36.4%] and 63 [78.8%] and 34 (34.0%) respectively, p&lt;0.001 (figure). Patients receiving PVI+PW+NPV ablation, showed significantly higher success than those with PVI alone or amiodarone (p &lt;0.001). The outcome in the PVI alone group was not different from AMIO group (p= 0.67). No patient was lost to follow-up during the study period. At the time of analysis, all recurrence-free patients had completed ≥6 month follow-up. Conclusion: This randomized study shows that PVI alone has a low success rate similar to Amiodarone when compared to PVI plus posterior wall plus non pv trigger in patients with heart failure and persistent AF.

The effect of visual feedback and training in auditory-perceptual judgment of voice quality

The aim of the present investigation was to evaluate the effect of visual feedback on rating voice quality severity level and the reliability of voice quality judgment by inexperienced listeners. For this purpose two training programs were created, each lasting 2 hours. In total 37 undergraduate speech–language therapy students participated in the study and were divided into a visual plus auditory-perceptual feedback group (V + AF), an auditory-perceptual feedback group (AF), and a control group with no feedback (NF). All listeners completed two rating sessions judging overall severity labeled as grade (G), roughness (R), and breathiness (B). The judged voice samples contained the concatenation of continuous speech and sustained phonation. No significant rater reliability changes were found in the pre- and posttest between the three groups in every GRB-parameter (all p > 0.05). There was a training effect seen in the significant improvement of rater reliability for roughness within the NF and AF groups (all p < 0.05), and for breathiness within the V + AF group (p < 0.01). The rating of the severity level of roughness changed significantly after the training in the AF and V + AF groups (p < 0.01), and the breathiness severity level changed significantly after the training in the V + AF group (p < 0.01). The training of V + AF and AF may only minimally influence the reliability in the judgment of voice quality but showed significant influence on rating the severity level of GRB parameters. Therefore, the use of both visual and auditory anchors while rating as well as longer training sessions may be required to draw a firm conclusion.

Abstract 3460: Fetal alcohol exposure increases susceptibility to carcinogenesis in the pituitary

Abstract The idea that exposure to adverse environmental conditions and lifestyle choices during pregnancy can result in fetal programming that underlies disease susceptibility in adulthood is now widely accepted. Fetal alcohol exposed offspring display many behavioral and physiological abnormalities including neuroendocrine-immune functions, which often carry over into their adult life. Since neuroendocrine-immune system is critically involved in the regulation of tumor surveillance, we determined whether fetal alcohol exposure increases the susceptibility to estrogen-induced pituitary prolactin-secreting tumors (prolactinomas), commonly occurring pituitary tumors in humans. Pregnant Fischer 344 rats were fed between gestational days 7 and 21 with a liquid diet containing alcohol (AF), pair-fed with isocaloric liquid diet (PF), or fed ad libitum with rat chow (AD). At 90 days of age, female offspring rats were ovariectomized and received a subcutaneous estradiol implant. These rats were sacrificed between 4 and 5 months after the estradiol implants. At the time of sacrifice, pituitaries of these animals were inspected for tumor and whole body were inspected for any tumor metastasis. Estradiol treatment increased pituitary weight about 5-folds in AD and PF treated groups and increased 20-30-folds in the AF treated group. Most tumors in the AF group were hemorrhagic. About 30% AF rats had some tumors in the non-pituitary sites. AD and PF rats did not show any non-pituitary site tumor. When AF rat pituitaries were grown in cultures, cells rapidly grew and formed colonies. Colony formation and rapid growth rate were not observed in cells of the pituitary from PF and AD rats. Histopathological evaluation revealed that tumors in AF group were more densely packed cells as compare to the PF and AD groups who showed uniform cells with abundant cytoplasm. Pituitary tumor from alcohol exposed animals showed strong nuclear p53 and monoclonal Ki67 immunoreactivity in almost all tumor cells. Significantly higher mRNA levels of hemorrhage-associated genes (VEGF and MMP-9) were also observed in pituitary tumor tissues from AF group as compare with PF and AD groups. Tumor cells showed positivity to prolactin staining but showed negativity to other pituitary hormones staining. Histological evaluation of the pituitary tissues revealed that tumors were prolactin producing in all groups, and tumors in AF pituitaries were highly proliferative. These data provide evidence for aggressive, possible neoplastic, prolactinoma development in the pituitary after estrogen treatment in fetal alcohol exposed female rats. (This work is supported by a National Institute of Health grant R01 AA11591). Citation Format: Shaima Jabbar, George Maglakelidze, Dipak K. Sarkar. Fetal alcohol exposure increases susceptibility to carcinogenesis in the pituitary. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3460. doi:10.1158/1538-7445.AM2015-3460