Incremental healthcare cost burden in patients with atrial flutter only.

Background: Limited information is available on the costs related to atrial flutter only. This study provides a comprehensive estimate of the cost in patients with atrial flutter only versus matched patients without any atrial arrhythmia. Methods: Patients over 20 years of age with a minimum of one inpatient or two outpatient diagnosis codes for atrial flutter in 2005 and a minimum of 12 months of continuous enrollment pre- and post-index were identified using the MarketScan Commercial and Medicare databases. Atrial flutter patients were propensity matched to patients without atrial arrhythmias. Total costs for each patient for 12 months post-index were calculated. National cost was estimated using the projected prevalence of atrial flutter for 2010. Results: A total of 1,042 patients with atrial flutter only were successfully matched with comparison patients. For atrial flutter patients compared to matched controls without atrial arrhythmias, total mean annual cost per patient was 81% higher ($23,008 vs. $12,717) and mean annual inpatient expenditure was 214% higher ($8,518 vs. $2,713). When applied to national atrial flutter prevalence data, total incremental cost burden was estimated to be $687.9 million per year more than patients without atrial arrhythmias, primarily due to cardiovascular specific expenditure ($377 million, 55% of total) with 58% ($218.5 million) of the increased inpatient expenditure due to cardiovascular specific admissions and $159 million (23%) for atrial flutter specific care. Sex-related differences were also present in atrial flutter only patients. Conclusion: Although atrial flutter-only patients are less prevalent than atrial fibrillation patients, the national incremental cost burden in atrial flutter is substantial on a per-patient level.

Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise.

Background: The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model. Methods: Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts. Seven pigs underwent electrophysiology study with venous arterial-extra corporeal membrane oxygenation (VA-ECMO) support. Tissue thickness, scar and heterogeneous tissue (HT) transmurality were calculated at the location of the diastolic electrograms of mapped VT-HC. Results: Diastolic locations had median scar transmurality of 33.1% and a median HT transmurality 7.6%. Diastolic activation was found within areas of non-transmural scar in 80.1% of cases. Tissue activated during the diastolic component of VT circuits was thinner than healthy tissue (median thickness: 5.5 mm vs. 8.2 mm healthy tissue, p < 0.0001) and closer to HT (median distance diastolic tissue: 2.8 mm vs. 11.4 mm healthy tissue, p < 0.0001). Non-scarred regions with diastolic activation were closer to steep gradients in thickness than non-scarred locations with normal EGMs (diastolic locations distance = 1.19 mm vs. 9.67 mm for non-diastolic locations, p < 0.0001). Sites activated late in diastole were closest to steep gradients in tissue thickness. Conclusions: Non-transmural scar, mildly decreased tissue thickness, and steep gradients in tissue thickness represent the structural characteristics of the diastolic component of reentrant circuits in VT-HC in this porcine model and could form the basis for imaging criteria to define ablation targets in future trials.

An image segmentation technique with statistical strategies for pesticide efficacy assessment.

Image analysis is a useful technique to evaluate the efficacy of a treatment for weed control. In this study, we address two practical challenges in the image analysis. First, it is challenging to accurately quantify the efficacy of a treatment when an entire experimental unit is not affected by the treatment. Second, RGB codes, which can be used to identify weed growth in the image analysis, may not be stable due to various surrounding factors, human errors, and unknown reasons. To address the former challenge, the technique of image segmentation is considered. To address the latter challenge, the proportion of weed area is adjusted under a beta regression model. The beta regression is a useful statistical method when the outcome variable (proportion) ranges between zero and one. In this study, we attempt to accurately evaluate the efficacy of a 35% hydrogen peroxide (HP). The image segmentation was applied to separate two zones, where the HP was directly applied (gray zone) and its surroundings (nongray zone). The weed growth was monitored for five days after the treatment, and the beta regression was implemented to compare the weed growth between the gray zone and the control group and between the nongray zone and the control group. The estimated treatment effect was substantially different after the implementation of image segmentation and the adjustment of green area.

Logistic Regression Models with Unspecified Low Dose-Response Relationships and Experimental Designs for Hormesis Studies.

Hormesis refers to a nonmonotonic (biphasic) dose-response relationship in toxicology, environmental science, and related fields. In the presence of hormesis, a low dose of a toxic agent may have a lower risk than the risk at the control dose, and the risk may increase at high doses. When the sample size is small due to practical, logistic, and ethical considerations, a parametric model may provide an efficient approach to hypothesis testing at the cost of adopting a strong assumption, which is not guaranteed to be true. In this article, we first consider alternative parameterizations based on the traditional three-parameter logistic regression. The new parameterizations attempt to provide robustness to model misspecification by allowing an unspecified dose-response relationship between the control dose and the first nonzero experimental dose. We then consider experimental designs including the uniform design (the same sample size per dose group) and the c -optimal design (minimizing the standard error of an estimator for a parameter of interest). Our simulation studies showed that (1) the c -optimal design under the traditional three-parameter logistic regression does not help reducing an inflated Type I error rate due to model misspecification, (2) it is helpful under the new parameterization with three parameters (Type I error rate is close to a fixed significance level), and (3) the new parameterization with four parameters and the c -optimal design does not reduce statistical power much while preserving the Type I error rate at a fixed significance level.

Voltage during atrial fibrillation is superior to voltage during sinus rhythm in localizing areas of delayed enhancement on magnetic resonance imaging: An assessment of the posterior left atrium in patients with persistent atrial fibrillation.

BACKGROUND: Bipolar electrogram voltage during sinus rhythm (VSR) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent atrial fibrillation (AF), but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance. OBJECTIVE: The purpose of this study was determine whether, given adequate temporal sampling, the spatial distribution of mean AF voltage (VmAF) better correlates with delayed-enhancement magnetic resonance imaging (MRI-DE)-detected atrial fibrosis than VSR. METHODS: AF was mapped (8 seconds) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660 ± 28 points/map). After cardioversion, VSR was mapped (557 ± 326 points/map). Electroanatomic and MRI-DE maps were co-registered in 14 patients. RESULTS: The time course of VmAF was assessed from 1-40 AF cycles (∼8 seconds) at 1113 locations. VmAF stabilized with sampling >4 seconds (mean voltage error 0.05 mV). Paired point analysis of VmAF from segments acquired 30 seconds apart (3667 sites; 15 patients) showed strong correlation (r = 0.95; P <.001). Delayed enhancement (DE) was assessed across the posterior left atrial (LA) wall, occupying 33% ± 13%. VmAF distributions were (median [IQR]) 0.21 [0.14-0.35] mV in DE vs 0.52 [0.34-0.77] mV in non-DE regions. VSR distributions were 1.34 [0.65-2.48] mV in DE vs 2.37 [1.27-3.97] mV in non-DE. VmAF threshold of 0.35 mV yielded sensitivity of 75% and specificity of 79% in detecting MRI-DE compared with 63% and 67%, respectively, for VSR (1.8-mV threshold). CONCLUSION: The correlation between low-voltage and posterior LA MRI-DE is significantly improved when acquired during AF vs sinus rhythm. With adequate sampling, mean AF voltage is a reproducible marker reflecting the functional response to the underlying persistent AF substrate.

Imaging assessment of a portable hemodialysis device: detection of possible failure modes and monitoring of functional performance.

BACKGROUND: The purpose of this study was to investigate the utility and limitations of various imaging modalities in the noninvasive assessment of a novel compact hemodialyzer under development for renal replacement therapy, with specific aim towards monitoring its functional performance. METHODS: The prototype is a 4×3×6 cm aluminum cartridge housing "blood" and "dialysate" flow paths arranged in parallel. A sheet of semipermeable silicon nanopore membranes forms the blood-dialysate interface, allowing passage of small molecules. Blood flow was simulated using a peristaltic pump to instill iodinated contrast through the blood compartment, while de-ionized water was instilled through the dialysate compartment at a matched rate in the countercurrent direction. Images were acquired under these flow conditions using multi-detector computed tomography (MDCT), fluoroscopy, high-resolution quantitative computed tomography (HR-QCT), and magnetic resonance imaging (MRI). MDCT was used to monitor contrast diffusion efficiency by plotting contrast density as a function of position along the path of flow through the cartridge during steady state infusion at 1 and 20 mL/min. Both linear and exponential regressions were used to model contrast decay along the flow path. RESULTS: Both linear and exponential models of contrast decay appeared to be reasonable approximations, yielding similar results for contrast diffusion during a single pass through the cartridge. There was no measurable difference in contrast diffusion when comparing 1 mL/min and 20 mL/min flow rates. Fluoroscopy allowed a gross qualitative assessment of flow within the device, and revealed flow inhomogeneity within the corner of the cartridge opposite the blood inlet port. MRI and HR-QCT were both severely limited due to the paramagnetic properties and high atomic number of the target material, respectively. During testing, we encountered several causes of device malfunction, including leak formation, trapped gas, and contrast-mediated nanopore clogging. We illustrate the imaging manifestations of each. CONCLUSIONS: Despite the inherent challenges in imaging a predominantly metallic device, some modalities show potential in the non-invasive assessment of a novel compact hemodialyzer. The approaches described here could potentially be translated to device evaluation in the implanted setting.

Regional myocardial wall thinning at multidetector computed tomography correlates to arrhythmogenic substrate in postinfarction ventricular tachycardia: assessment of structural and electrical substrate.

BACKGROUND: A majority of patients undergoing ablation of ventricular tachycardia have implanted devices precluding substrate imaging with delayed-enhancement MRI. Contrast-enhanced multidetector computed tomography (MDCT) can depict myocardial wall thickness with submillimetric resolution. We evaluated the relationship between regional myocardial wall thinning (WT) imaged by MDCT and arrhythmogenic substrate in postinfarction ventricular tachycardia. METHODS AND RESULTS: We studied 13 consecutive postinfarction patients undergoing MDCT before ablation. MDCT data were integrated with high-density 3-dimensional electroanatomic maps acquired during sinus rhythm (endocardium, 509±291 points/map; epicardium, 716±323 points/map). Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were assessed with regard to the WT. A significant correlation was found between the areas of WT <5 mm and endocardial low voltage (correlation-R=0.82; P=0.001), but no such correlation was found in the epicardium. The WT <5 mm area was smaller than the endocardial low-voltage area (54 cm(2) [Q1-Q3, 46-92] versus 71 cm(2) [Q1-Q3, 59-124]; P=0.001). Among a total of 13 060 electrograms reviewed in the whole study population, 538 LAVA were detected and analyzed. LAVA were located within the WT <5 mm (469/538 [87%]) or at its border (100% within 23 mm). Very late LAVA (>100 ms after QRS complex) were almost exclusively detected within the thinnest area (93% in the WT<3 mm). CONCLUSIONS: Regional myocardial WT correlates to low-voltage regions and distribution of LAVA critical for the generation and maintenance of postinfarction ventricular tachycardia. The integration of MDCT WT with 3-dimensional electroanatomic maps can help focus mapping and ablation on the culprit regions, even when MRI is precluded by the presence of implanted devices.

Model uncertainty and model averaging in the estimation of infectious doses for microbial pathogens.

Food-borne infection is caused by intake of foods or beverages contaminated with microbial pathogens. Dose-response modeling is used to estimate exposure levels of pathogens associated with specific risks of infection or illness. When a single dose-response model is used and confidence limits on infectious doses are calculated, only data uncertainty is captured. We propose a method to estimate the lower confidence limit on an infectious dose by including model uncertainty and separating it from data uncertainty. The infectious dose is estimated by a weighted average of effective dose estimates from a set of dose-response models via a Kullback information criterion. The confidence interval for the infectious dose is constructed by the delta method, where data uncertainty is addressed by a bootstrap method. To evaluate the actual coverage probabilities of the lower confidence limit, a Monte Carlo simulation study is conducted under sublinear, linear, and superlinear dose-response shapes that can be commonly found in real data sets. Our model-averaging method achieves coverage close to nominal in almost all cases, thus providing a useful and efficient tool for accurate calculation of lower confidence limits on infectious doses.

Intraprocedural use of ibutilide to organize and guide ablation of complex fractionated atrial electrograms: preliminary assessment of a modified step-wise approach to ablation of persistent atrial fibrillation.

INTRODUCTION: While able to achieve clinical success, the current step-wise approach to persistent atrial fibrillation (AF) ablation requires considerable "substrate" ablation and frequently mandates multiple procedures to address consequent atrial tachycardias (ATs). An alternative strategy minimizing the amount of ablation while maintaining clinical success would be desirable. We hypothesize that intraprocedural administration of a low-dose antiarrhythmic drug (AAD) during AF will organize areas of passive activation and not affect areas critical to AF maintenance, thereby potentially minimizing the ablation lesion set. METHODS AND RESULTS: Eleven patients (age = 55 +/- 6 years; LA = 48 +/- 15 mm; median AF duration = 3 years) with persistent AF undergoing catheter ablation were enrolled in this exploratory prospective observational study. After pulmonary vein (PV) isolation, a mean cycle length (mCL) map was created and areas with mCL <120 ms were considered to represent complex fractionated atrial electrograms (CFAE). Ibutilide (0.25-1.0 mg) was then administered and a second mCL map created. Ablation lesions were placed at CAFE sites identified after ibutilide administration. Activation and/or entrainment mapping was employed to address ATs. The endpoint of ablation was achieving sinus rhythm. The average LA mCL increased (146 vs 165 ms, P = 0.01) and the LA CFAE surface area decreased after ibutilide administration. Additional ablation organized AF to either sinus rhythm or AT in 10/11 (91%) patients. After a median follow up of 455 days, 8 of 11 (72%) patients were free from AF. Three patients underwent a repeat ablation procedure (average 1.27 ablations/patient). CONCLUSIONS: Ibutilide administration may organize atrial activity and facilitate AF termination during ablation while minimizing the ablation lesion set.