Citations

IntroductionAdjudication of thousands of implantable cardioverter defibrillator (ICD)‐treated arrhythmia episodes is labor intensive and, as a result, is most often left undone. The objective of this study was to evaluate an automatic classification algorithm for adjudication of ICD‐treated arrhythmia episodes.MethodsThe algorithm uses a machine learning algorithm and was developed using 776 arrhythmia episodes. The algorithm was validated on 131 dual‐chamber ICD shock episodes from 127 patients adjudicated by seven electrophysiologists (EPs). Episodes were classified by panel consensus as ventricular tachycardia/ventricular fibrillation (VT/VF) or non‐VT/VF, with the resulting classifications used as the reference. Subsequently, each episode electrogram (EGM) data was randomly assigned to three EPs without the atrial lead information, and to three EPs with the atrial lead information. Those episodes were also classified by the automatic algorithm with and without atrial information. Agreement with the reference was compared between the three EPs consensus group and the algorithm.ResultsThe overall agreement with the reference was similar between three‐EP consensus and the algorithm for both with atrial EGM (94% vs 95%, P = 0.87) and without atrial EGM (90% vs 91%, P = 0.91). The odds of accurate adjudication, after adjusting for covariates, did not significantly differ between the algorithm and EP consensus (odds ratio 1.02, 95% confidence interval: 0.97–1.06).ConclusionsThis algorithm performs at a level comparable to an EP panel in the adjudication of arrhythmia episodes treated by both dual‐ and single‐chamber ICDs. This type of algorithm has the potential for automated analysis of clinical ICD episodes, and adjudication of EGMs for research studies and quality analyses.

Objective: We evaluate the prevalence, etiology, and outcomes of hypoglycemia requiring emergency medical services (EMS) in patients without diabetes mellitus (non-DM). Methods: We reviewed medical records of all ambulance calls for non-DM with blood glucose <70 mg/dl in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2009. Results: A total of 131 patients (age 51 ± 19 years; 54 % females) made 142 EMS calls, while 10 patients made repeated calls. Causes of hypoglycemia were critical illness (42; 32%), alcohol and polysubstance use (36; 27.5 %), insulinoma/ bariatric surgery (10; 8%), restricted oral intake (7; 5%), and multiple factors (3; 27.5 %). Patients with alcohol and polysubstance abuse were younger ( p = .002). A total of 54 patients had additional hypoglycemia predisposing comorbidities/factors [adrenal insufficiency (2), end-stage renal disease (11) and chronic liver disease (7), beta blockers use (34), and pentamidine use (1)]. Repeated calls and emergency room transportation were similar, but hospitalization varied across the etiologies, with the lowest proportion in the multiple-factor-related hypoglycemia group ( p = .01). Duration of follow-up was 1.28 (interquartile range 0.13–2.70) years. A total of 38 patients died, and age-adjusted mortality varied across different etiologies ( p < .001), with highest among critically ill. Cancer caused the highest number of deaths (7/38; 18%), while 1 death was due to hypoglycemia. Conclusions: There were multiple etiologies for hypoglycemic episodes in community-dwelling non-DM that required EMS. Critical illness, multifactorial causes, and alcohol/polysubstance abuse were common causes. Hospitalization and mortality were higher with critical illnesses.

Abstract A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P &lt; 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.

Summary A low‐diversity microbial community, dominated by the γ ‐proteobacterium H alomonas sulfidaeris , was detected in samples of warm saline formation porewater collected from the C ambrian Mt. S imon S andstone in the I llinois B asin of the N orth A merican M idcontinent (1.8 km/5872 ft burial depth, 50° C , pH 8, 181 bars pressure). These highly porous and permeable quartz arenite sandstones are directly analogous to reservoirs around the world targeted for large‐scale hydrocarbon extraction, as well as subsurface gas and carbon storage. A new downhole low‐contamination subsurface sampling probe was used to collect in situ formation water samples for microbial environmental metagenomic analyses. Multiple lines of evidence suggest that this H . sulfidaeris ‐dominated subsurface microbial community is indigenous and not derived from drilling mud microbial contamination. Data to support this includes V 1‐ V 3 pyrosequencing of formation water and drilling mud, as well as comparison with previously published microbial analyses of drilling muds in other sites. Metabolic pathway reconstruction, constrained by the geology, geochemistry and present‐day environmental conditions of the Mt . S imon S andstone, implies that H . sulfidaeris ‐dominated subsurface microbial community may utilize iron and nitrogen metabolisms and extensively recycle indigenous nutrients and substrates. The presence of aromatic compound metabolic pathways suggests this microbial community can readily adapt to and survive subsurface hydrocarbon migration.

Introduction Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF). While it is known the severity of left atrial (LA) enlargement affect the success of AF ablation, little is known the impact of intracardiac pressure on the ablation outcome. Methods This prospective study consisted of 63 patients (mean age 57±9 years, 73% male) who underwent catheter-based pulmonary vein isolation for drug refractor symptomatic AF (48% paroxysmal, 52% persistent). All patients underwent simultaneous echocardiography and haemodynamic measurements including left ventricular end systolic pressure (LVEDP), mean left atrial pressure (LAP) and dP/dtmax using Millar catheter at the time of procedure during AF. Left atrial volume (LAV) was measure by biplane area length method. Recurrence of AF was defined as episodes of AF more than 5 min documented in 24h ambulatory ECG or event monitor. Results After a mean follow-up duration of 16±7 months, AF elimination off anti-arrhythmic drugs was achieved in 70 % (44/63) of patients. Among the echographic and haemodynamic measurements, the baseline LAV and mean LAP were 57.62±25.39 ml and 12.19±4.57 mm Hg in AF free patients compared to 81.20±40.88 ml (p=0.02) and 16.46±4.14 mm Hg (p=0.01) in AF recurrence groups. Univariate and multivariate analysis showed LAP was the only independent predictor of the recurrence with an adjusted odd ratio of 1.27 (95% CI 1.04 to 1.54, p=0.03, table). Conclusion LAP is a determinant of AF recurrence after AF ablation. Therapies towards reduction of LA filling pressure, especially in patients with elevated LAP, may improve the outcome of ablation. Table Baseline clinical characters in the recurrence group and non-recurrence group Non-recurrence (N=44) recurrence (N=19) Univariate Multivariate P 95% CI P 95% CI Age (ys) 57.39±9.92 59.26±10.47 0.49 0.97, 1.08 – – AF type, persistent AF no. (%) 23 (53%) 10 (50%) 0.97 0.34, 2.98 – – AF duration (ys) 5.84±5.43 8.08±7.66 0.20 0.99, 1.05 – – LA volume (mL) 57.62±25.39 81.20±40.88 0.02 1.01, 1.05 0.30 0.99, 1.05 LVEDP (mm Hg) 10.25±14.54 11.25±5.75 0.81 0.96, 1.06 – – dP/dt max (mm Hg/s) 1294.02±337.13 1211.77±225.36 0.47 0.99, 1.02 – – Mean LAPmean (mm Hg) 12.19±4.57 16.46±4.14 0.01 1.06, 1.50 0.02 1.04, 1.54 Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF) but the success rate ranged wide. This study aimed to investigate the effect of LAP on AF recurrence.

Background Neurohormonal dysregulation contributes to heart failure (HF) progression. We sought to determine the effect of cardiac resynchronisation therapy (CRT) on the nerve growth factor (NGF), a biomarker that promotes the maturation, and survival of sympathetic nerve endings, and amino-terminal propeptide of type III procollagen (PIIINP), a marker of type III collagen synthesis. Methods This prospective study enrolled 20 healthy age-matched controls and 45 consecutive patients (pts) who received CRT-D. NYHA class, distance of 6-min walk and echocardiography and plasma concentrations of NGF, PIIINP, b-type natriuretic peptide (BNP), norepinephrine (NE), epinephrine (EPI) and dopamine (DA) were measured before and 6 month after CRT. Response to CRT was defined as ≥15% reduction in left ventricular end-systolic volume index (LVESVI) at 6-month follow-up. Results The baseline BNP (557±692 vs 47±35, p<0.01) and PIIINP (8.22±3.76 vs 5.36±1.47, p<0.01) were elevated in HF compared to controls, while NGF, NE, EPI and DA levels were not different. Twenty two of 45 pts (49%) responded to CRT. The responder group demonstrated significant decrease only in BNP level (p=0.04) at 6-month follow-up, parallelling with the clinical improvements (table 1). The baseline PIIINP was lower in CRT responders than non-responders (p=0.04), and it correlated with the reduction of LVESVI (p=0.01, r=−0.50) after CRT. The further multivariate analysis showed only the plasma PIIINP level among clinic characters and all the biomarkers can predict the improvement of LVESV index (OR=8.33, P=0.01). Conclusion The low PIIINP level, which is consistent with possible less cardiac fibrosis and a more plastic ventricle at baseline, is associated with CRT responsiveness. Contrary to previous reports, the NGF levels were not reduced during HF and that there was no NGF rebound in CRT responders.

Introduction Lateral or posteriolateral coronary vein has been considered the optimal location of left ventricular (LV) lead placement for cardiac resynchronisation therapy (CRT). However, the long-term clinical outcomes of CRT based on LV lead location have not been sufficiently addressed. Methods Seven hundred and eighteen CRT-P/CRT-D recipients from Jan 2002 to Dec 2008 were studied. At the CRT implant, the LV lead placement was prioritised as posterolateral/lateral (PL, 50%), anterior lateral (AL, 31%), anterior interventricular (AI, 12%) or middle cardiac veins (MC, 7%). NYHA class and echocardiography were assessed before and after CRT. Clinical outcomes of CRT were compared among 4 LV lead locations. Results Patient baseline demographics, except the gender (P=0.03), were similar among four groups. After CRT, the improvement in NYHA class, LV ejection fraction (EF), and LV diastolic diameter were significantly improved comparably across four LV lead locations (table). The increase in LVEF by >5% were 46%, 47%, 41% and 42% in PL, AL, AI and MC groups (p=0.87). Conclusion The present study suggests that LV lead positioned in the alternative coronary veins, other than posteriolateral or lateral location, achieve comparable benefit in improvement of HF symptoms, and LV function after CRT. Table Comparison of clinic outcomes before and after CRT in different LV lead locations Lateral vein (N=359) Anterolateral vein (N=226) middle cardiac vein (N=49) anterior interventricular vein (N=84) Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT NYHA 3.02±0.46 2.34±0.81* 2.92±0.53 2.34±0.89* 3.10±0.45 2.70±0.85* 2.98±0.52 2.43±0.86* LVEF (%) 23.57±7.28 30.82±11.67* 24.19±7.96 30.44±12.06* 24.97±7.62 30.72±11.43* 22.45±7.25 28.40±11.73* LVEDD (mm) 65.71±9.12 63.00±9.73* 65.79±8.87 63.88±9.88* 65.39±9.32 62.61±10.25* 68.48±8.92 64.86±9.67* LVESD (mm) 57.91±9.89 52.83±11.68* 56.69±10.23 53.03±12.01* 56.18±11.56 52.24±13.11* 59.09±10.04 55.32±13.30 RVD (mm) 0.90±0.86 0.82±0.85 0.85±0.92 0.82±0.85 0.86±0.83 1.01±0.84 0.56±0.77 0.78±0.91 RV dysfunction 1.05±0.92 0.88±0.92* 1.03±0.93 0.93±0.91 1.06±0.97 1.06±0.90 0.74±0.86 0.79±0.96 MR (m/s) 1.54±0.78 1.30±0.75* 1.57±0.83 1.35±0.75* 1.53±0.71 1.15±0.70* 1.36±0.69 1.19±0.68 * P<0.05 compared to pre-CRT.