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Graphical abstract, Highlights • Barlow's disease is a degenerative mitral valvulopathy with highly complex anatomy. • Barlow's disease is classically unfavorable for TMVr using MitraClip. • Patients with Barlow's disease, SAM, and high surgical risk may be candidates for TMVr.

Echocardiography is a key tool in the management of patients with pulmonary arterial hypertension (PAH), but many potential parameters could be used to assess response to therapy. In this retrospective study of 48 patients with severe PAH at baseline, we examined echocardiographic variables before and after initiation of PAH-specific therapy to evaluate which measures of right ventricular (RV) function best correlated with clinical response to therapy as assessed by 6-minute walk distance (6MWD) and 3-year all-cause mortality. Tricuspid annular plane systolic excursion (TAPSE), mid-RV and basal-RV diameters, RV systolic pressure, and RV global longitudinal strain were all found to significantly improve after initiation of a PAH therapy. Decreases in right atrial area (r = -0.50, p = 0.002) and mid-RV diameter (r = -0.36, p = 0.03) were most strongly correlated with improvement in 6MWD. Pretreatment values of RA area (hazard ratio [HR] per 1 SD: 2.72; 95% confidence interval [CI] 1.58, 4.69), mid-RV diameter (HR 2.03; 1.20, 3.45), basal-RV diameter (HR 2.27; 1.40, 3.70), and RV global longitudinal strain (HR 2.36; 1.22, 4.56) were all associated with mortality risk. 6MWD and TAPSE were the 2 variables for which pretreatment measures (6MWD - HR 0.35; 0.17, 0.72; TAPSE - HR 0.41; 0.21, 0.82) and change with treatment (6MWD - HR 0.26; 0.10, 0.64; TAPSE - HR 0.40; 0.21, 0.77) were both significantly associated with 3-year mortality. Change in RV systolic pressure with treatment was significantly associated with mortality (HR 2.55; 1.23, 5.28,) but pretreatment baseline had no association (HR 1.48; 0.72, 3.06). Although many echocardiographic parameters change with initiation of PAH treatment, the strong association of both baseline TAPSE and change in TAPSE with mortality supports the ongoing use of TAPSE as an important measure in the assessment of disease severity and treatment response in PAH.

There is considerable interest in AI systems that can assist a cardiologist to diagnose echocardiograms, and can also be used to train residents in classifying echocardiograms. Prior work has focused on the analysis of a single frame. Classifying echocardiograms at the video-level is challenging due to intra-frame and inter-frame noise. We propose a two-stream deep network which learns from the spatial context and optical flow for the classification of echocardiography videos. Each stream contains two parts: a Convolutional Neural Network (CNN) for spatial features and a bi-directional Long Short-Term Memory (LSTM) network with Attention for temporal. The features from these two streams are fused for classification. We verify our experimental results on a dataset of 170 (80 normal and 90 abnormal) videos that have been manually labeled by trained cardiologists. Our method provides an overall accuracy of 91.18%, with a sensitivity of 94.11% and a specificity of 88.24%.

IMPORTANCE: Patients with abnormal (positive) exercise electrocardiography, but normal stress echocardiography (+ECG/−Echo) are commonly encountered in clinical practice; however, the prognostic significance of this discordant result is unclear. OBJECTIVE: To determine whether patients with +ECG/−Echo have a higher rate of adverse clinical events and a poorer prognosis than patients with negative exercise ECG and normal stress Echo imaging (−ECG/−Echo). DESIGN, SETTING, AND PARTICIPANTS: Between January 1, 2000, and February 28, 2014, a total of 47 944 consecutive patients without known coronary artery disease who underwent exercise stress Echo at Duke University Medical Center were evaluated for inclusion in this observational cohort study. Data analysis was conducted from January 1, 2000, to December 31, 2016. INTERVENTIONS/EXPOSURES: Patients were categorized as having −ECG/−Echo, +ECG/−Echo, or +Echo (−ECG/+Echo and +ECG/+Echo). MAIN OUTCOMES AND MEASURES: The primary outcome was a composite end point of death, myocardial infarction, hospitalization for unstable angina, and coronary revascularization. Secondary outcomes included individual adverse events and downstream testing. RESULTS: After excluding submaximal tests and nondiagnostic ECG or stress imaging results, 15 077 patients (mean [SD] age, 52 [13] years; 6228 [41.3%] men) were classified by stress test results. Of these, 12 893 patients (85.5%) had −ECG/−Echo, 1286 patients (8.5%) had +ECG/−Echo, and 898 patients (6.0%) had +Echo. Through a median follow-up of 7.3 (interquartile range, 4.4-10.0) years, the composite end point occurred in 794 patients with −ECG/−Echo (8.5%), 142 patients with +ECG/−Echo (14.6%), and 297 patients with +Echo (37.4%). Death occurred in 425 patients with −ECG/−Echo (4.8%), 50 patients with +ECG/−Echo (5.9%), and 70 patients with +Echo (11.2%). Myocardial infarction occurred in 195 patients with −ECG/−Echo (2.2%), 31 patients with +ECG/−Echo (3.6%), and 59 patients with +Echo (8.7%). The addition of stress ECG findings to clinical and exercise data yielded incremental prognostic value. Patients with −ECG/−Echo imaging results had the least downstream testing (2.3%), followed by +ECG/−Echo (12.8%), and +Echo (33.6%) (P

BACKGROUND Pulmonary hypertension (PH) is frequently reported in patients with advanced chronic kidney disease and is associated with early allograft failure and death. However, the causes of PH are heterogeneous, and patient prognosis may vary by etiologic subtype. METHODS Data from the University of North Carolina Cardiorenal Registry were examined to determine associations between PH, with or without elevated left atrial pressure (eLAP), and mortality in candidates for kidney transplantation. PH and eLAP were determined by Doppler echocardiography and by tissue Doppler imaging, respectively. RESULTS From 2006 to 2013, 778 registry patients were screened preoperatively by echocardiography. Most patients were black (64%) and men (56%); the mean age was 56 years. PH was identified in 97 (12%) patients; of these, eLAP was prevalent in half. During a median follow-up of 4.4 years, 179 (23%) received a kidney transplant, and 195 (25%) died. After adjustments for demographics, comorbidities, dialysis vintage, and kidney transplantation, PH was associated with twice the 5-year mortality (hazard ratio [HR] = 2.11; 95% confidence interval [CI]: 1.48-3.03), with stronger associations in the absence of eLAP (HR = 2.87; 95% CI: 1.83-4.49) than with eLAP (HR = 1.11; 95% CI: 0.57-2.17), P for interaction = 0.01. CONCLUSIONS The mortality risk associated with PH among patients with advanced chronic kidney disease appears to differ by etiology. Patients with PH in the absence of eLAP are at high risk of death and in need of focused attention. Future research efforts should investigate potential strategies to improve outcomes for these patients.

Objective Progression of mitral regurgitation (MR) after orthotopic lung transplantation (OLT) may be an underrecognized phenomenon due to the overlapping symptomatology of pulmonary and valvular disease. Literature evaluating the progression of MR after OLT currently is limited to case reports. Therefore, the hypothesis that MR progresses after OLT was tested and the association of preprocedure MR with postoperative mortality was assessed. Design A retrospective cohort. Setting A tertiary-care hospital. Participants Patients who underwent OLT between January 1, 2003 and February 4, 2012. Interventions After receiving institutional review board approval, a preprocedure transesophageal echocardiogram was compared with a postoperative transthoracic echocardiogram (TTE) to determine the progression of MR. Univariate and multivariate association between preprocedure MR grade and 1- and 5-year mortality was assessed. A p value of

This retrospective study evaluated the diagnostic characteristics of a combination of echocardiographic parameters for pulmonary hypertension (PH). Right ventricular systolic pressure (RVSP) estimation by echocardiography (echo) is used to screen for PH. However, the sensitivity of this method is suboptimal. We hypothesized that RVSP estimation in conjunction with other echo parameters would improve the value of echo for PH. The Duke Echo database was queried for adult patients with known or suspected PH who had undergone both echo and right heart catheterization (RHC) within a 24 h period between 1/1/2008 and 12/31/2013. Patients with complex congenital heart disease, heart transplantation, ventricular assist device, or on mechanical ventilation at time of study were excluded. Diagnostic characteristics of several echo parameters (right atrial enlargement, pulmonary artery (PA) enlargement, RV enlargement, RV dysfunction, and RVSP) for PH (mean PA pressure 25 mmHg on RHC) were evaluated among 1007 patients. RVSP ≥40 had a sensitivity of 77% (accuracy 77), while RVSP ≥35 had the highest sensitivity at 88% (81% accuracy). PA enlargement had the lowest sensitivity at 17%. The area under the curve (AUC) for RVSP was 0.844. A model including RVSP, RA, PA, RV enlargement and RV dysfunction had a higher AUC (AUC = 0.87) than RVSP alone. The value of echo as a screening test for PH is improved by a model incorporating a lower RVSP in addition to other right heart parameters. These findings need to be validated in prospective cohorts.

Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects.

Background Chronic kidney disease ( CKD ) is an adverse prognostic marker for valve intervention patients; however, the prevalence and related outcomes of valvular heart disease in CKD patients is unknown. Methods and Results Included patients underwent echocardiography (1999–2013), had serum creatinine values within 6 months before index echocardiogram, and had no history of valve surgery. CKD was defined as diagnosis based on the International Classification of Diseases, Ninth Revision or an estimated glomerular filtration rate 2 . Qualitative assessment determined left heart stenotic and regurgitant valve lesions. Cox models assessed CKD and aortic stenosis ( AS ) interaction for subsequent mortality; analyses were repeated for mitral regurgitation ( MR ). Among 78 059 patients, 23 727 (30%) had CKD ; of these, 1326 were on hemodialysis. CKD patients were older; female; had a higher prevalence of hypertension, hyperlipidemia, diabetes, history of coronary artery bypass grafting/percutaneous coronary intervention, atrial fibrillation, and heart failure ≥mild AS; and ≥mild MR (all P AS for CKD patients were 40%, 34%, and 42%, respectively, and 69%, 54%, and 67% for non‐CKD patients. Five‐year survival estimates of mild, moderate, and severe MR for CKD patients were 51%, 38%, and 37%, respectively, and 75%, 66%, and 65% for non‐CKD patients. Significant interaction occurred among CKD , AS / MR severity, and mortality in adjusted analyses; the CKD hazard ratio increased from 1.8 (non‐ AS patients) to 2.0 (severe AS ) and from 1.7 (non‐ MR patients) to 2.6 (severe MR ). Conclusions Prevalence of at least mild AS and MR is substantially higher and is associated with significantly lower survival among patients with versus without CKD . There is significant interaction among CKD , AS / MR severity, and mortality, with increasingly worse outcomes for CKD patients with increasing AS / MR severity.

For the 2015 American College of Cardiology Scientific Sessions in San Diego, California, several Duke Cardiology fellows decided to try something different. Instead of staying in private hotel rooms, we rented a house in Old Town San Diego where we stayed together in a family-style atmosphere. We

Background— The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. Methods and Results— The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography–catheterization difference of P =0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI ( P Conclusions— A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies.

Myocardial elasticity is an important indicator of cardiac function and is affected in many disorders associated with heart failure. Ultrasound based interrogation of cardiac stiffness has been extensively studied in ex-vivo, open chest and intracardiac imaging environments. The ability to make these measurements robustly through non-invasive means such as transthoracic imaging would make them more clinically viable and widely applicable. However, transthoracic imaging is a challenging environment for displacement estimation due to poor SNR, acoustic clutter and complex cardiac motion. This work aims to address some of those challenges on a clinical ultrasound system. Sequences to make M-mode measurements of acoustic radiation force induced displacements in the heart over the entire cardiac cycle were implemented on the Siemens SC2000 and a cardiac phased array probe. Pulse inversion harmonic tracking was employed on the tracking beams to suppress the effect of stationary clutter on displacement estimation. Two families of motion filters, high pass filters and polynomial fit filters were analyzed for their performance in being able to remove the background cardiac motion and isolate the radiation force induced tissue response. Clinical data was acquired on 4 subjects and analyzed for repeatability of diastolic vs. systolic displacements. A high pass filter with a cutoff of 100 Hz and a 2nd order polynomial fit filter were found to be equally effective in suppressing intrinsic motion. Diastolic-to-systolic displacement ratios measured in the interventricular septum ranged from 1.3 to 2.2 across subjects but were found to be fairly consistent between the parasternal long axis and the parasternal short axis views for each subject.

Background In patients with suspected native valve infective endocarditis, current guidelines recommend initial transthoracic echocardiography (TTE) followed by transesophageal echocardiography (TEE) if clinical suspicion remains. The guidelines do not account for the quality of initial TTE or other findings that may alter the study's diagnostic characteristics. This may lead to unnecessary TEE when initial TTE was sufficient to rule out vegetation. Methods The objective of this study was to determine if the use of a strict definition of negative results on TTE would improve the performance characteristics of TTE sufficiently to exclude vegetation. A retrospective analysis of patients at a single institution with suspected native valve endocarditis who underwent TTE followed by TEE within 7 days between January 1, 2007, and February 28, 2014, was performed. Negative results on TTE for vegetation were defined by either the standard approach (no evidence of vegetation seen on TTE) or by applying a set of strict negative criteria incorporating other findings on TTE. Using TEE as the gold standard for the presence of vegetation, the diagnostic performance of the two transthoracic approaches was compared. Results In total, 790 pairs of TTE and TEE were identified. With the standard approach, 661 of the transthoracic studies had negative findings (no vegetation seen), compared with 104 studies with negative findings using the strict negative approach (meeting all strict negative criteria). The sensitivity and negative predictive value of TTE for detecting vegetation were substantially improved using the strict negative approach (sensitivity, 98% [95% CI, 95%–99%] vs 43% [95% CI, 36%–51%]; negative predictive value, 97% [95% CI, 92%–99%] vs 87% [95% CI, 84%–89%]). Conclusions The ability of TTE to exclude vegetation in patients is excellent when strict criteria for negative results are applied. In patients at low to intermediate risk with strict negative results on TTE, follow-up TEE may be unnecessary.

To evaluate the use of surrogate measures in pulmonary hypertension (PH) clinical trials and how it relates to clinical practice.Studies of pulmonary arterial hypertension (PAH) employ a variety of surrogate measures in addition to clinical events because of a small patient population, participant burden, and costs. The use of these measures in PH drug trials is poorly defined.We searched PubMed/MEDLINE/Embase for randomized or prospective cohort PAH clinical treatment trials from 1985 to 2013. Extracted data included intervention, trial duration, study design, patient characteristics, and primary and secondary outcome measures. To compare with clinical practice, we assessed the use of surrogate measures in a clinical sample of patients on PH medications at Duke University Medical Center between 2003 and 2014.Between 1985 and 2013, 126 PAH trials were identified and analyzed. Surrogate measures served as primary endpoints in 119 trials (94.0%). Inclusion of invasive hemodynamics decreased over time (78.6%, 75.0%, 52.2%; P for trend = .02), while functional testing (7.1%, 60.0%, 81.5%; P for trend.0001) and functional status or quality of life (0%, 47.6%, 62.8%; P for trend.0001) increased in PAH trials over the same time periods. Echocardiography data were reported as a primary or secondary outcome in 32 trials (25.4%) with increased use from 1985-1994 to 1995-2004 (7.1% vs 35.0%, P = .04), but the trend did not continue to 2005-2013 (25.0%). In comparison, among 450 patients on PAH therapies at our institution between 2003 and 2013, clinical assessments regularly incorporated serial echocardiography and 6-minute walk distance tests (92% and 95% of patients, respectively) and repeat measurement of invasive hemodynamics (46% of patients).The majority of PAH trials have utilized surrogate measures as primary endpoints. The use of these surrogate endpoints has evolved significantly over time with increasing use of patient-centered endpoints and decreasing or stable use of imaging and invasive measures. In contrast, imaging and invasive measures are commonly used in contemporary clinical practice. Further research is needed to validate and standardize currently used measures.

Although exercise stress echocardiography has been used for over 20 years, uncertainty remains regarding discordant electrocardiography (ECG) and echocardiogram (echo) results in patients without known coronary artery disease (CAD). In particular, the prognostic significance of positive ECG in the

The authors hypothesized that average precardiopulmonary bypass (pre-CPB) transesophageal echocardiographic (TEE) mean gradient (PGm) and aortic valve area (AVA) values would be significantly different from preoperative transthoracic (TTE) values in the same patients and that these changes would affect pre-CPB TEE grading of aortic stenosis (AS).Retrospective, observational design.Single university hospital.The study comprised 92 patients who underwent aortic valve replacement with or without coronary artery bypass grafting between 2000 and 2012 at Duke University Hospital and who had PGm and AVA values recorded in both pre-CPB TEE and preoperative TTE reporting databases.None.PGm with pre-CPB TEE was lower by 6.6 mmHg (95% confidence interval, -4.0 to -9.3 mmHg; p0.001), whereas AVA was higher by 0.10 cm(2) (95% confidence interval, 0.04 to 0.15 cm(2); p0.001), compared with preoperative TTE values. When using PGm, pre-CPB TEE generated an AS severity 1 grade lower 39.1% of the time and revealed no difference 55.4% of the time compared to preoperative TTE. When using AVA by continuity, pre-CPB TEE generated an AS severity 1 grade lower 14.1% of the time and revealed no difference 81.5% of the time compared to preoperative TTE. When using either PGm or AVA, preoperative TTE exhibited moderate or severe AS for all study patients, whereas, pre-CPB TEE demonstrated mild AS in 5.4% (n = 92) of patients.The authors confirmed their hypothesis that pre-CPB TEE generates different PGm and AVA values compared with preoperative TTE. These differences often underestimate AS severity. Hemodynamic standardizations or adjustments of pre-CPB TEE PGm and AVA values may be necessary in anesthetized patients before assigning an AS grade using these parameters.

Introduction: Aortic valve replacement (AVR) for aortic stenosis (AS) carries additional surgical risk in patients with left ventricular dysfunction (LVD) but has been associated with survival benefit. The current use of AVR and its relationship to mortality in patients with moderate or severe AS and LVD is ill defined. Hypothesis: We hypothesized that AVR was underutilized among patients with moderate/severe AS and LVD, and that it was associated with lower mortality. Methods: We queried the Duke Echocardiographic Database for patients with moderate (mean gradient >25 mmHg and/or peak velocity >3m/s) or severe AS (mean gradient >40 mmHg and or peak velocity >4m/s) and LVD (left ventricular ejection fraction [LVEF] Results: We identified a total of 1,634/132,804 patients with moderate (1,095, 67%) or severe (539, 33%) AS and LVD. Severe LVD (LVEF ≤35%) was present in 35% of the cohort. The median age of the cohort was 75 (IQR 67-83), and patients with moderate AS were more likely than those with severe AS to have a history of ischemic heart disease, diabetes, peripheral vascular disease, cerebrovascular disease, and renal disease (all p Median follow-up time was 1.2 years (IQR 0.2- 3.9). There were 863 deaths in the cohort. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. After multivariable adjustment, AVR with (n=270) or without CABG (n=280), compared to medical therapy was associated with lower mortality (HR=0.47 [0.38, 0.59], p Conclusions: Among patients with significant AS and LVD, AVR with or without CABG is associated with significant mortality benefit and may be underutilized in this population. Further research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.

BACKGROUND: Transesophageal echocardiography (TEE) is often recommended to exclude infective endocarditis (IE) in patients presenting with bacteremia despite a negative transthoracic echocardiogram (TTE). Previous studies showing inadequate sensitivity of TTE for native valve endocarditis are dated, and do not reflect modern advances in ultrasound image optimization technology. We hypothesized that with current generation echocardiography technology, a TTE absent mobile echo targets and without significant valvular abnormalities would have sufficient negative predictive value to exclude IE. METHODS: The Duke Echocardiographic Database was queried from 1/1/2007 [[Unable to Display Character: –]] 2/28/2014 for TTEs performed within 7 days prior to a TEE ordered for bacteremia/endocarditis. The dominant imaging platform used for both TTE and TEE during this era was the Philips IE33, with frequent use of fundamental frequencies to enhance spatial resolution beyond that of harmonic imaging alone. TTE studies identified as having poor sound transmission were excluded. A normal TTE was defined by the demonstration of normal cardiac anatomy, at most trivial valvular regurgitation, and absence of valvular stenosis, mobile/oscillating echo targets on valves, and hardware including catheters. The demonstration of an oscillating target on TEE along with clinical criteria based on chart review defined IE. RESULTS: A total of 974 unique patients had a TTE followed by a TEE within a week. IE was suggested in 209 of these patients by TEE. Among 107 patients meeting the a priori normal criteria on TTE, 3 patients had an abnormal TEE consistent with IE. These results correspond to a negative predictive value (NPV) of 97.2% (95% C.I. 91.4% - 99.3%) for a normal TTE to exclude IE. CONCLUSIONS: In this retrospective analysis from an academic medical center echocardiography laboratory, we demonstrated that an adequate quality TTE alone in a patient with a structurally normal heart without indwelling hardware has a high NPV for IE. Current TTE image optimization approaches may obviate the need to pursue TEE in patients after a recent preceding normal TTE.

Heart rate variability (HRV) falls in humans with sepsis, but the mechanism is not well understood. We utilized a mouse model of endotoxemia to test the hypothesis that cytokines play a role in abnormal HRV during sepsis. Adult male C57BL/6 mice underwent surgical implantation of probes to continuously monitor electrocardiogram and temperature or blood pressure via radiotelemetry. Administration of high-dose LPS ( Escherichia coli LPS, 10 mg/kg, n = 10) caused a biphasic response characterized by an early decrease in temperature and heart rate at 1 h in some mice, followed by a prolonged period of depressed HRV in all mice. Further studies showed that LPS doses as low as 0.01 mg/kg evoked a significant decrease in HRV. With high-dose LPS, the initial drops in temperature and HR were temporally correlated with peak expression of TNFα 1 h post-LPS, whereas maximal depression in HRV coincided with peak levels of multiple other cytokines 3–9 h post-LPS. Neither hypotension nor hypothermia explained the HRV response. Pretreatment with dexamethasone prior to LPS significantly blunted expression of 7 of the 10 cytokines studied and shortened the duration of depressed HRV by about half. Interestingly, dexamethasone treatment alone caused a dramatic increase in both low- and high-frequency HRV. Administration of recombinant TNFα caused a biphasic response in HR and HRV similar to that caused by LPS. Understanding the role of cytokines in abnormal HRV during sepsis could lead to improved strategies for detecting life-threatening nosocomial infections in intensive care unit patients.

The Global Reference Analysis and Visualization Environment (GRAVE) is a research prototype multimedia system that manages a diverse variety of data types and presents them to the user in a format that is geographically referenced ton the surface of a globe. When the user interacts with the globe, the system automatically manages the `level-of-detail' issues to support these user actions (allowing flexible functionality without sacrificing speed or information content). To manage the complexity of the presentation of the (visual) information to the user, data instantiations may be represented in an iconified format. When the icons are picked, or selected, the data `reveal' themselves in their `native' format. Object-oriented programming and data type constructs were employed, allowing a single`look and feel' to be presented to the user for the different media types. GRAVE currently supports the following data types: imagery (from various sources of differing resolution, coverage, and projection); elevation data (from DMA and USGS); physical simulation results (atmospherics, geological, hydrologic); video acquisitions; vector data (geographical, political boundaries); and textual reports. GRAVE was developed in the Application Visualization System (AVS) Visual Programming Environment (VPE); as such it is easily modifiable and reconfigurable, supporting the integration of new processing techniques/approaches as they become available or are developed.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.