Applying a technology-based system for weight loss in adults with obesity.

OBJECTIVE: The aim of this study was to compare an in-person, group-based behavioral weight loss intervention to technology-based interventions in adults with obesity. METHODS: Adults (N = 39; body mass index: 39.5 ± 2.8 kg m-2; age: 39.9 ± 11.5 years) participated in a 6-month program with randomization to one of three intervention groups: standard behavioral weight loss, a technology-based system combined with a monthly intervention telephone call (TECH) or an enhanced technology-based system combined with a monthly intervention telephone call (EN-TECH). All groups were prescribed an energy-restricted diet and physical activity. Assessments occurred at 0, 3 and 6 months. Separate mixed-effects models using unstructured dependence structure were fit to the outcomes. RESULTS: Weight loss (least square means ± standard error) at 6 months was -6.57 ± 1.65 kg in standard behavioral weight loss, -5.18 ± 1.72 kg in TECH and -6.25 ± 1.95 kg in EN-TECH (p-value for time effect ≤ 0.0001). A similar pattern was observed for change in body mass index, waist circumference and percent body fat. There was a decrease in total energy intake (p = 0.0005) and percent dietary fat intake (p = 0.0172), and physical activity increased (p = 0.0003). CONCLUSIONS: Findings provide initial information on the use of technology-based interventions that include wearable devices combined with brief monthly telephone calls for weight loss in adults with obesity.

Estimation of the costs of acute gastrointestinal illness in British Columbia, Canada.

The costs associated with gastrointestinal infection (GI) in the province of British Columbia, Canada, were estimated using data from a population-based survey in three health service delivery areas, namely Vancouver, East Kootenay and Northern Interior. The number of cases of disease, consequent expenditure of resources and associated economic costs were modeled as probability distributions in a stochastic model. Using 2004 prices, the estimated mean annual cost per capita of gastrointestinal infection was CAN$128.61 (207.96 euros), with a mean annual cost per case of CAN$1,342.57 (2,170.99 euros). The mean estimate of the overall economic burden to British Columbia was CAN$514.2 million (831.5 million euros) (95% CFI CAN$161.0 million to CAN$5.8 billion; 260.3 million euros to 9.38 billion euros). The major element of this cost was the loss of productivity associated with time away from paid employment by both the sick and their caregivers. Sensitivity analysis suggested that the uncertainty associated with the base model assumptions did not significantly affect the estimates. The results are comparable to those obtained in an earlier study using a similar analytical framework and data from the city of Hamilton, Ontario, Canada.

Drinking water consumption patterns in British Columbia: an investigation of associations with demographic factors and acute gastrointestinal illness.

A cross-sectional telephone survey was performed in the province of British Columbia, Canada, to investigate drinking water consumption patterns and their associations with various demographic characteristics and acute gastrointestinal illness (AGI). Water consumption included plain water and water used in the preparation of cold beverages. The median amount of water consumed daily was four-250 mL servings (1.0 L), although responses were highly variable (0 to 9.0 L). Alternative water use was common: bottled water was the primary source of drinking water (i.e. >or=75% of the total daily water intake) for 23% of respondents and 47% of households used in-home water treatment methods. Approximately 10% of respondents reported an episode of AGI (vomiting or diarrhea) in the previous 4-week period. Such illness was associated with age (continuous variable in years, OR=-0.98), sex (male vs. female, OR=0.8) and the amount of water consumed (continuous variable in 250-mL servings, OR=1.06); however, a causal relationship with water consumption cannot be established based on this study alone. Overall, the associations of drinking water patterns with age, sex, education, and household income serve as important reminders to researchers and public health professionals of the non-uniform nature of drinking water consumption, and indicate potential differences in exposure to waterborne hazards in this population.

Frequency-based analysis of diastolic function: detrimental phase-shift of the pressure-flow relation characterizes the 'delayed relaxation'; transmitral flow pattern.

Cardiologists assess the filling (diastolic) function (DF) of the heart by visually determining whether Doppler echocardiographic transmitral E-waves appear to have "normal", "delayed-relaxation" or "constrictive restrictive" patterns. To achieve a causal method of quantitative DF assessment we present a frequency-based approach. In analogy to impedance of electrical circuits, we characterize DF by analysis of the left ventricular (LV) diastolic pressure (P) to transmitral flow (Q) relation during the Doppler E-wave in the frequency domain in terms of Z(omega) = P(omega) / Q(omega), characteristic and input impedance. This allows DF to be expressed in terms of a complex reflection coefficient R* =/R*/e(iphi). Twenty subjects had simultaneous pressure-flow data recorded during catheterization, were dichotomized according to deceleration time (DT) and had E-waves subjected to model-based image processing (MBIP) to determine model parameter c, related to E-wave deceleration. Results show that phase angle phi is linearly related to c ; that both phi and c were significantly different (p < 0.05) between the short (n=12) and long (n=8) DT group. We conclude that the 'delayed relaxation'; pattern is associated with deviation of the phase angle phi from its optimal (pi) value that minimizes reflection and maximizes filling, resulting in modification of the optimal pressure - flow relation in early diastole.

Echocardiographic characterization of fundamental mechanisms of abnormal diastolic filling in diabetic rats with a parameterized diastolic filling formalism.

Abnormalities of diastolic function (DF) precede systolic dysfunction in diabetic cardiomyopathy. Transmitral Doppler flow analysis is the primary method for noninvasively assessing DF. We used model-based Doppler E-wave analysis to evaluate diastolic function differences between normal and diabetic rat hearts. Control rats and those with diabetes underwent echocardiography with analysis by traditional Doppler indexes and by the parameterized diastolic filling (PDF) formalism, generating 3 parameters, x0, c, and k, that uniquely characterize each E-wave. Significant intergroup differences in the E/A ratios (P <.01), isovolumic relaxation times (P <.01), and the modeling parameter c (P <.05) were found. There were no significant differences in shortening fraction, deceleration time, myocardial collagen content, or the parameters x0 and k between diabetic and control rats. These results indicate that differences in diastolic function may be noninvasively quantified and that diabetic hearts may exhibit defects in uncoupling of the contractile apparatus without concomitant increases in chamber stiffness.

Chamber properties from transmitral flow: prediction of average and passive left ventricular diastolic stiffness.

A chamber stiffness (K(LV))-transmitral flow (E-wave) deceleration time relation has been invasively validated in dogs with the use of average stiffness [(DeltaP/DeltaV)(avg)]. K(LV) is equivalent to k(E), the (E-wave) stiffness of the parameterized diastolic filling model. Prediction and validation of 1) (DeltaP/DeltaV)(avg) in terms of k(E), 2) early rapid-filling stiffness [(DeltaP/DeltaV)(E)] in terms of k(E), and 3) passive (postdiastasis) chamber stiffness [(DeltaP/DeltaV)(PD)] from A waves in terms of the stiffness parameter for the Doppler A wave (k(A)) have not been achieved. Simultaneous micromanometric left ventricular (LV) pressure (LVP) and transmitral flow from 131 subjects were analyzed. (DeltaP)(avg) and (DeltaV)(avg) utilized the minimum LVP-LV end-diastolic pressure interval. (DeltaP/DeltaV)(E) utilized DeltaP and DeltaV from minimum LVP to E-wave termination. (DeltaP/DeltaV)(PD) utilized atrial systolic DeltaP and DeltaV. E- and A-wave analysis generated k(E) and k(A). For all subjects, noninvasive-invasive relations yielded the following equations: k(E) = 1,401. (DeltaP/DeltaV)(avg) + 59.2 (r = 0.84) and k(E) = 229.0. (DeltaP/DeltaV)(E) + 112 (r = 0.80). For subjects with diastasis (n = 113), k(A) = 1,640. (DeltaP/DeltaV)(PD) - 8.40 (r = 0.89). As predicted, k(A) showed excellent correlation with (DeltaP/DeltaV)(PD); k(E) correlated highly with (DeltaP/DeltaV)(avg). In vivo validation of average, early, and passive chamber stiffness facilitates quantitative, noninvasive diastolic function assessment from transmitral flow.

Phase plane analysis of left ventricular hemodynamics.

We sought to extract additional physiological information from the time-dependent left ventricular (LV) pressure contour and thereby gain new insights into ventricular function. We used phase plane analysis to characterize high-fidelity pressure data in selected subjects undergoing elective cardiac catheterization. The standard hemodynamic indexes of LV systolic and diastolic function derived from the time-dependent LV pressure contour could be easily obtained using the phase plane method. Additional novel attributes of the phase plane pressure loop, such as phase plane pressure loop area, graphical representation of the isovolumic relaxation time constant, and quantitative measures of beat-to-beat systolic-diastolic coupling were characterized. The asymmetry between the pressures at which maximum isovolumic pressure rise and pressure fall occur, as well as their load dependence, were also easily quantitated. These results indicate that the phase plane method provides a novel window for physiological discovery and has theoretical and applied advantages in quantitative ventricular function characterization.

The relation of the peak Doppler E-wave to peak mitral annulus velocity ratio to diastolic function.

Previous observations (Garcia et al. 1998; Sohn et al. 1997; Nagueh et al. 1997) indicate that mitral annulus velocity may be viewed as a "load-independent" index of filling and that wedge pressure is linearly related to the transmitral flow velocity (V(E)) to mitral annulus velocity (V(MA)) ratio (V(E)/V(MA)) measured at maximum velocity. In healthy subjects, the mean value observed for [V(E)](max)/[V(MA)](max) was 1:0.23 approximately 4. No prior physiologic or physical explanation for the basis of, or for the magnitude of, the ratio has been proposed. We propose a physiologic, model-based, quantitative explanation for these observations and test our simplified model's prediction in an invasive (n = 30) and noninvasive (n = 34) test groups of subjects. The simplified geometric model is based on the known constant volume (within a few percentage points) attribute of the four-chambered heart. Accordingly, left-atrial and left-ventricular volumes reciprocate so that their sum is constant throughout the cardiac cycle. The model predicts that: 1. the ratio (V(E)/V(MA)) is a constant approximately 3 in healthy hearts; and 2. V(E)/V(MA) should be linearly proportional to left ventricular end-diastolic pressure (LVEDP). Model prediction was tested using V(E) and V(MA) echocardiographic data from 34 subjects (noninvasive group), and simultaneous echocardiographic and high-fidelity hemodynamic (LVEDP) data in 30 subjects (invasive group). Excellent agreement was observed between model prediction and observed data. For the noninvasive (healthy) group, [V(E)](max)/[V(MA)](max) = 4.20 +/- 1.11. For the invasive group, [V(E)](max)/[V(MA)](max) was observed to be linearly related to LVEDP, [V(E)](max)/[V(MA)](max) = 0.19 (LVEDP) + 1.54, r = 0.92. Hence, [V(E)](max)/[V(MA)](max) is a legitimate flow-derived index of diastolic function because it is a derivable consequence of the heart's constant-volume pump attribute.

Modeling of diastole.

Modeling methods have been employed to further characterize the physical and physiologic processes of filling and diastolic function. They have led to more detailed understanding of the effect of alteration of physiologic parameters on the Doppler E-wave contour as well as pulmonary vein flow. Depending on the modeling approach, different aspects of the filling process have been considered from AV gradient and net compliance to atrial appendage function to the mechanical suction pump attribute of the heart. The models have been applied for further characterization of diastolic function and elucidation of novel basic physiologic relations. We trust that readers recognize that this article could not serve as a comprehensive and global review of the state-of-the-art in physiologic modeling, but rather as a selective overview, with emphasis on the main modeling principles and options currently in use. Modeling of systems physiology, especially as it relates to the function of the four-chamber heart, remains a fertile area of investigation. Future progress is likely to have profound influence on (noninvasive) diagnosis and quantitation of the effect of therapy and lead to continued discovery of "new" (macroscopic, cellular, and molecular biologic) physiology.

Unsolved problems in diastole.

It is now recognized that a sizable portion of patients who exhibit symptoms of congestive heart failure have relatively well-preserved systolic function, but have significantly elevated LV filling pressures. This syndrome, termed "diastolic heart failure," is associated with various conditions such as aging, anatomic abnormalities, hypertension, ischemic disease, tachycardia, and atrial fibrillation. Advances in the proper medical and surgical management of these patients will depend on the continued delineation of the basic physiologic mechanisms that account for normal and pathologic cardiac diastolic function. This goal can only be achieved by the integration of information acquired from basic science investigations conducted in vitro and in vivo, mathematic modeling simulation studies, and prospective, community-based investigations that characterize the incidence, prevalence, and natural history of the disease. In addition, randomized clinical trials will be needed to determine the optimal treatment strategies for this group of patients--strategy choices undoubtably complicated by a disease whose treatment is influenced to a large extent by its origin. The future therapies evaluated in these randomized clinical trials will most likely range from medical therapies that target either the heart directly or the peripheral vascular system, to surgical interventions such as direct myocardial revascularization, to gene therapy. Finally, it is worth mentioning one more unresolved issue that is of general practical concern not only to the physiologist studying diastolic function, but also to the clinician: whether or not it is even feasible to develop a single, sensitive, specific, clinically relevant index of diastolic function that is free from the contaminating influences of rate, contractility, and load. As observed by Glantz 20 years ago, developing indexes with the hope that one might fully delineate the left ventricle's diastolic properties, rather than concentrating on discovering the physiologic significance of such indexes, is probably counterproductive. More recently, in a related article, Slinker implied that an operational definition of any aspect of cardiac function must allow for the measurement of that function over an adequate range of essential variables. Therefore, as previously mentioned, the physiologist studying cardiac function has the daunting task of trying to understand, in a precise way, how the processes and mechanisms of the various phases of the cardiac cycle couple together to produce either a normal or abnormal functioning heart. It seems clear that because of the complex weave of factors that control overall cardiac diastolic function, the derivation of any single index that adequately describes LV diastolic function in vivo may not be possible.

Prognostic value of diastolic filling parameters derived using a novel image processing technique in patients > or = 70 years of age with congestive heart failure.

Conventional echocardiographic characterization of diastolic function requires manual analysis of Doppler E-and A-wave amplitudes, deceleration times, isovolumic relaxation times, and pulmonary venous flow patterns. Mathematic modeling of the suction pump activity of the heart permits characterization of diastolic function through model-based image processing, which relies solely on transmitral Doppler images. This automated method uniquely specifies the entire E-wave contour using 3 parameters (x(o), k, and c) that determine E-wave amplitude, width, and rate of decay. Moreover, the index beta = c2 - 4k, reflecting the balance between chamber viscosity and stiffness/recoil, represents a novel parameter for characterizing diastolic function. We analyzed Doppler E waves from 39 patients (mean age 79 years, 61% women, mean ejection fraction 47%) using the model-based image processing technique. A value of beta <-900 was selected as indicative of severe diastolic dysfunction. Of 17 subjects with beta <-900, 8 (47%) were no longer alive at 1 year. Of 22 subjects with beta >-900, all were alive (p = 0.001). The index beta, dichotomized at <-900, had a predictive accuracy of 0.769 (30 of 39), a negative predictive value of 1.0 (22 of 22 alive), and a positive predictive value of 0.471 (8 of 17 deceased) for 1-year vital status. Of 14 subjects with deceleration time < or =160 ms, 5 (36%) were deceased at 1 year, whereas for deceleration time >160 ms, 22 of 25 patients were alive (p = NS). Of 16 subjects with ejection fraction <45%, 6 (38%) were deceased at 1 year. Of 23 subjects with ejection fraction >45%, 21 were alive at 1 year (p = 0.074). On multivariate analysis, beta dichotomized at -900 was the strongest independent predictor of 1-year mortality. We conclude that evaluation of diastolic function using model-based image processing provides valuable prognostic information in elderly patients with heart failure.

Pharmacokinetics and protein binding of eprosartan in hemodialysis-dependent patients with end-stage renal disease.

STUDY OBJECTIVES: To compare eprosartan pharmacokinetics in hemodialysis patients and in volunteers with normal renal function, and to determine the effect of hemodialysis on these values. DESIGN: Open-label, parallel-group, single-dose study. SETTING: Outpatient hemodialysis treatment center and an industry-affiliated clinical pharmacology unit. PATIENTS: Ten healthy volunteers and nine hemodialysis patients. INTERVENTION: A single oral dose of eprosartan 400 mg was administered to volunteers on 1 day and to patients on 2 days (a nondialysis and a dialysis day). Patients underwent high-flux hemodialysis. MEASUREMENTS AND MAIN RESULTS: Concentrations of eprosartan in plasma and dialysate were assayed by high-performance liquid chromatography; plasma protein binding was determined by ultrafiltration. Eprosartan pharmacokinetics showed greater variability in patients than in volunteers. However, six of nine patients had exposures that were within the range observed for volunteers. Mean total AUC(0-t) was increased approximately 60% (95% CI-22, 225) in patients. Total Cmax was similar between groups (PE = 1.01, 95% CI -40, 71). Mean percent fraction unbound (%f(u)) in patients (3.02%) was significantly greater than that in volunteers (1.74%). Unbound AUC(0-t) and unbound Cmax were, on average, approximately 172% (95% CI 28, 479) and 73% (95% CI -1, 199) greater, respectively, in patients. After hemodialysis, the mean %f(u) decreased from 3.19-2.01%. Mean recovery of eprosartan in dialysate was 6.8 mg (range 0-23.1 mg) and hemodialytic clearance was approximately 11 ml/minute, which does not represent a significant portion of total clearance. CONCLUSIONS: Eprosartan was safe and well tolerated in both groups. Based on its known safety profile and because of its exaggerated pharmacokinetic variability in patients undergoing hemodialysis, treatment should be individualized based on tolerability and response. Supplemental doses of eprosartan after hemodialysis are unnecessary.

Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: intraindividual variability and correlation under basal conditions and conditions of CYP 3A4 induction.

A single spot urine collection to measure the ratio of 6 beta-hydroxycortisol (6 beta-OHC) to free cortisol (C) has been proposed as a research tool for the assessment of CYP3A4 induction. However, intraindividual variability in 6 beta-OHC/C under basal conditions and conditions of induction has not been prospectively evaluated, and findings on the correlation between morning spot and 24-hour urinary ratios have been conflicting. In this study, the variability in morning spot and 24-hour urinary 6 beta-OHC/C ratios was assessed in 15 healthy adult male volunteers before, during, and after oral administration of rifampin 600 mg once daily for 14 days. In addition, the correlation between morning spot and 24-hour urinary ratios measured under baseline, maximum induction, and postinduction was determined. Intraindividual coefficients of variation (CVs) at baseline for the morning spot and 24-hour ratios were 54.3% and 57.1%, respectively, and were not changed significantly during induction. No significant differences were detected in the variability between the morning spot and 24-hour ratios at baseline, maximum induction, or postinduction. A good correlation (r = 0.61, p < 0.0001) was detected between the mean morning spot and 24-hour urinary ratios. Mean (+/- SEM) percent increases in the morning spot and 24-hour ratios at maximum induction relative to baseline were 320% +/- 73% and 137% +/- 30%, respectively (p = 0.019). All 15 subjects had an increase in the mean morning spot ratio at maximum induction relative to baseline, whereas 12 subjects showed an increase in the mean 24-hour ratio. The time course of changes in the mean morning spot urinary ratio in response to a 14-day course of rifampin was also similar to that reported previously in a study using 24-hour urine collections. These findings suggest that measurement of the morning spot urinary 6 beta-OHC/C ratio is an effective and efficient method for evaluating the potential of investigational agents to induce CYP3A4.

Blood pool agent strongly improves 3D magnetic resonance coronary angiography using an inversion pre-pulse.

The ability of a blood pool contrast agent to enhance MR coronary angiography was defined. The proximal coronary vessels of pigs were imaged before and after administration of Gd-DTPA bound covalently to bovine serum albumin (0.2 mmol/ kg). The contrast agent resulted in a reduction of the blood T1 value to 33+/-5 msec, as determined in vivo with a Look-Locker technique. Both 2D and 3D imaging techniques were performed. An inversion pulse suppressed the signal of nonblood tissue postcontrast. After contrast agent administration, in the 3D data set the signal-to-noise ratio (SNR) of blood and contrast-to-noise ratio (CNR) of blood to myocardium were improved by factors of 2.0+/-0.2 and 15+/-8, respectively (P < 0.05). Postcontrast, the 3D acquisition was superior to the 2D technique in terms of spatial resolution, SNR of blood, and CNR of blood to myocardium. The high contrast of the 3D data set allowed for direct and rapid display of coronary arteries using a "closest vessel projection."

Beat averaging alternatives for transmitral Doppler flow velocity images.

To characterize diastolic function from transmitral Doppler data, the image's maximum velocity envelope (MVE) is fit by a model for flow velocity. To reduce the physiologic beat-to-beat variability of best-fit determined model parameters, averaging of multiple cardiac cycles is indicated. To assess variability mathematically, we modeled physiologic noise as a random (normally-distributed) process and evaluated three methods of averaging (1, averaging model parameters from single images; 2, averaging images; and 3, averaging MVEs) using clinical datasets (50 continuous beats from 5 subjects). Method 2 generates a positive bias because low-velocity beats will not contribute to the composite MVE. The difference between Methods 3 and 1 is less than 2.0 E-5 (m/s)2 for uncorrelated model parameters. Input having 10% beat-to-beat variation yields a bias of <4% for model parameter mean. Hence, Method 1 was, in general, more robust than Method 3.

Urinary excretion of 6 beta-hydroxycortisol as an in vivo marker for CYP3A induction: applications and recommendations.

OBJECTIVE: To evaluate the usefulness of 6 beta-hydroxycortisol as a screen for CYP3A induction in early-phase drug development. METHODS: Five groups of 12 healthy elderly men were randomized to one of five treatment regimens: (1) 600 mg rifampin (INN, rifampicin) once daily, (2) placebo once daily, (3) 40 mg SB 216469 twice a day, (4) 60 mg SB 216469 twice a day, or (5) 40 mg SB 216469 three times a day. All medications were taken orally and administered for 7 consecutive days. Urine was collected over a 24-hour period for each subject before administration and on the last day of administration for each respective regimen for measurement of 6 beta-hydroxycortisol and 17-hydroxycorticosteroid concentrations. RESULTS: Subjects in the rifampin group had a significant increase from predose value in the 24-hour urinary excretion of 6 beta-hydroxycortisol and the ratio of 6 beta-hydroxycortisol to 17-hydroxycorticosteroid. All 12 subjects in the rifampin group had increases in 6 beta-hydroxycortisol excretion, whereas 11 of 12 had an increase in the ratio. The placebo and three active treatment groups did not show significant changes in either parameter. CONCLUSIONS: Urinary excretion of 6 beta-hydroxycortisol may be useful as a screening tool in early-phase development to assess the potential for an investigational drug to induce CYP3A.

Urine drug screening results from volunteers in phase I clinical pharmacology studies: are we being misled?

The general intent of phase I clinical pharmacology studies is to demonstrate the safety and tolerability of investigational new drugs in healthy human volunteers. There is emerging evidence that people who volunteer for these studies are not always truthful with investigators during the screening process. All healthy volunteers who participate in studies at the SmithKline Beecham Clinical Pharmacology Unit in Philadelphia, Pennsylvania, are required to submit to urine drug testing. During 11 months of 1996, a total of 1,469 urine samples were collected and tested for eight different drugs or classes of drugs of abuse. The urine samples collected during the first five months of 1996 were all analyzed using EMIT (Syva Corporation) and interpreted according to the guidelines established by the National Institutes of Drug Abuse (NIDA). Of 534 samples, 12 (2.2%) were reported as positive. During the last 6 months of 1996, a new methodology using a fluorescence polarization immunoassay (FPIA) was used. This assay had lower limits of quantification than EMIT, and more stringent interpretation guidelines than those of the NIDA were used. Of 935 samples analyzed by FPIA, 89 (9.5%) were positive. Of the 89 positive test results, 59 were below the cut-offs specified by the NIDA guidelines and would have been reported as negative. Interpretation of urine drug screen results according to the NIDA guidelines is not acceptable for clinical pharmacology investigations.

Evaluation of model-based processing algorithms for averaged transmitral spectral Doppler images.

In an effort to characterize more fully diastolic function using Doppler echocardiography, we have previously developed an automated method of model-based image processing for spectral Doppler images of transmitral blood flow. In this method, maximum velocity envelopes (MVEs) extracted from individual Doppler images are aligned and averaged over several cardiac cycles. The averaged waveform is fit by the solution of a kinematic model of diastolic filling. The results are estimates of the model parameters. As expected, the mean and standard deviation of the model parameter estimates depend on many factors such as noise, the number of cardiac cycles averaged, beat-to-beat variation, waveform shape, observation time and the processing methods used, among others. A comprehensive evaluation of these effects has not been performed to date. A simulation was developed to evaluate the performance of three automated processing methods and to measure the influence of noise, beat-to-beat variation and observation time on the model parameter estimates. The simulation's design and a description and analysis of the three automated processing methods are presented. Of the three methods evaluated, using the inflection point in the acceleration portion of the velocity contour as the first data point to be fit was found to be the most robust method for processing averaged E-wave MVE waveforms. Using this method under nominal conditions, the average bias was measured to be < 3% for each of the model parameters. As expected, the biases and standard deviations of the estimates increased as a result of increased noise levels, increased beat-to-beat variation and decreased observation time. Another important finding was that the effects of noise, beat-to-beat variation and waveform observation time on the parameter estimates are dependent on the location in model parameter space.

Can trasmitral Doppler E-waves differentiate hypertensive hearts from normal?

Physiological models of transmitral flow predict E-wave contour alteration in response to variation of model parameters (stiffness, relaxation, mass) reflecting the physiology of hypertension. Accordingly, analysis of only the E-wave (rather than the E-to-A ratio) should be able to differentiate between hypertensive subjects and control subjects. Conventional versus model-based image processing methods have never been compared in their ability to differentiate E-waves of hypertensive subjects with respect to age-matched control subjects. Digitally acquired transmitral Doppler flow images were analyzed by an automated model-based image processing method. Model-derived indexes were compared with conventional E-wave indexes in 22 subjects: 11 with hypertension and echocardiographically verified ventricular hypertrophy and 11 age-matched nonhypertensive control subjects. Conventional E-wave indexes included peak E, E, and acceleration and deceleration times. Model-based image processing-derived indexes included acceleration and deceleration times, potential energy index, and damping and kinematic constants. Intergroup comparison yielded lower probability values for model-based compared with conventional indexes. In the subjects studied, Doppler E-wave images analyzed by this automated method (which eliminates the need for hand-digitizing contours or the manual placement of cursors) demonstrate diastolic function alteration secondary to hypertension made discernible by model-based indexes. The method uses the entire E-wave contour, quantitatively differentiates between hypertensive subjects and control subjects, and has potential for automated noninvasive diastolic function evaluation in large patient populations, such as hypertension and other transmitral flow velocity-altering pathophysiological states.