Platelet Apoptotic Response May Be Associated With the Capacity of Aspirin to Inhibit Platelets.

An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.

Mitral valve navigator. A new diagnostic tool for effective regurgitant orifice quantification in mitral regurgitation.

INTRODUCTION: Mitral regurgitation severity assessment is usually carried out using qualitative, semiquantitative, and quantitative parameters. The mitral valve navigation (MVN) tool allows to measure the mitral effective regurgitant orifice (MERO) from 3D echo datasets. Our aim was to validate the MVN as a new tool to quantify MERO. A secondary aim was to assess the intra- and interobserver variability. METHODS: This is a retrospective study in which consecutive subjects undergoing a transoesophageal echocardiogram for more than mild mitral regurgitation evaluation were included. MERO measurement obtained by means of 3D color Doppler was used as the gold standard method for comparison. In every patient, MERO was also obtained using the MVN tool. RESULTS: Fifty-nine consecutive patients were analyzed (47.5% female; mean age 50.8 years). Mitral regurgitation was moderate in 23 (39%) and severe in 36 (61%) patients. Forty patients (67.8%) had a primary and 19 (32.2%) a secondary mitral regurgitation. The intraclass correlation coefficient (ICC) between 3D color Doppler and MVN was excellent (ICC: 0.95; 95% CI: 0.82 to 0.98; P < 0.001) in the total group and for patients with primary and secondary mitral regurgitation. Intra- and interobserver agreements were also good. CONCLUSIONS: Mitral valve navigator shows an excellent accuracy for measuring MERO when the transoesophageal 3D color Doppler is used as the reference method, either primary or secondary mitral regurgitation. Intraobserver reproducibility and interobserver reproducibility are also excellent. These findings make this software a good alternative method to measure mitral regurgitation severity.

FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms.

AIMS: To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus. METHODS: AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol l-1 rivaroxaban. RESULTS: AAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 levels released from AAA [Control: median: 23.45 (interquartile range: 16.17-37.15) vs. AAA: median: 153.07 (interquartile range: 100.80-210.69) pg ml-1  mg tissue-1 , P < 0.05] and the expression levels of nitric oxide synthase 2 were significantly higher in AAA than in control. The protein expression level of NADPH oxidase subunits gp67-and gp91-phox, but did not gp47-phox, were also significantly higher in the AAA sites than in control. Addition of rivaroxaban to AAA sites explants significantly reduced the release of interleukin-6 [median: 51.61 (interquartile range: 30.87-74.03) pg ml-1  mg tissue-1 , P < 0.05 with respect to AAA alone] and the content of nitric oxide synthase 2, gp67 and gp91-phox NADPH subunits. The content of matrix metallopeptidase 9 was significantly higher in the AAA sites as compared to control. Rivaroxaban also reduced matrix metallopeptidase 9 content in AAA sites to similar levels to control. CONCLUSIONS: FXa inhibition by rivaroxaban exerted anti-inflammatory and antioxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA.

Thromboembolic risk in atrial fibrillation: association between left atrium mechanics and risk scores. A study based on 3D wall-motion tracking technology.

BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a significantly high risk of stroke and systemic embolism. The aim of our study was to assess the association between left atrium (LA) mechanics measured by 3D wall-motion tracking (3DWMT) technology and the most common thromboembolic risk scores (CHADS2, CHA2DS2-VASc). METHODS: A total of 101 consecutive patients with permanent AF referred were included. Conventional bidimensional (2D) LA parameters, and LA mechanics by means of 3DWMT were studied. Association between LA 2D and 3DWMT parameters and both risk scores was evaluated as well as its correlation with every component of the score individually. RESULTS: Mean age was 78 ± 10 years. Mean CHADS2 was 2.7 ± 1.3 and mean CHA2DS2-VASc was 4.4 ± 1.7. Values of 2D and 3DWTM LA parameters were: 2D area 26.4 ± 9.7 cm(2) , 2D volume index 49.4 ± 10.1 mL/m(2) , 3DWMT left atrial emptying fraction (LAEF) 15.9 ± 8.4%, longitudinal strain 9.1 ± 4.5% and area strain 14.9 ± 8.8%. Linear regression analysis showed statistically significant correlation between LA longitudinal strain and LAEF with CHADS2 and CHA2DS2-VASc scores. For each 10% variation in longitudinal strain, CHADS2 and CHA2DS2-VASc scores change in 0.7 and 0.8 points, respectively. CONCLUSIONS: Left atrial longitudinal strain and emptying fraction assessed by 3D WMT technology have correlation with both CHADS2 and CHA2DS2-VASc scores. Each 10% of variation in longitudinal strain represents a 0.7 and 0.8 points change in those risk scores. LA mechanics evaluation might provide additional value to risk scores and could be considered to be a predictor of stroke in patients with AF.

[Validity and usefulness of B-type natriuretic peptide (BNP) for early detection of left ventricular dysfunction in high-risk patients in primary care]. / Validez y utilidad del péptido ventricular natriurético tipo B (BNP) en la detección de disfunción ventricular izquierda en pacientes de alto riesgo en atención primaria.

OBJECTIVE: The aim of this study was to determine the accuracy of BNP test for early diagnosis of left ventricular dysfunction in patients at high-risk for heart failure. DESIGN: Cross-sectional descriptive study. SETTING: 7 Primary Care Centres in Madrid (Spain). PARTICIPANTS: A consecutive sample of 204 consecutive asymptomatic patients with high risk for heart failure (Stages A-B, AHA/ACC Classification). MAIN MEASUREMENTS: BNP plasma levels were measured in the clinical setting using Triage BNP Test(®) (Biosite(®)) and an echocardiography was performed in the following 3 days in a single hospital unit as a reference standard. Plasma BNP levels were compared depending on the presence/absence of left ventricular dysfunction (LVD), type and severity degree. Sensitivity, specificity, positive and negative predictive values, and Área under the receiver operating characteristic curve (ROC) for BNP assay were calculated. RESULTS: BNP values were significantly higher (P<.001) in patients with left ventricular systolic dysfunction (LVSD). No significant differences were found for diastolic dysfunction. The best cut-off value to discriminate the patients with LVSD was 71.00 pg/ml, with an Área under the ROC curve of 0.757 (95% CI 0.64-0.87). Sensitivity for LVD diagnosis was 75% (95% CI 50.66-99.34), specificity 70.19% (95% CI 62.81-77.57), positive predictive value (PPV) 20% (95% CI 9.05-30.95), and negative predictive value (NPV) 96.58% (95% CI 92.86-100), with LVSD prevalence of 9.04% in this population. CONCLUSIONS: BNP determinations are of value in diagnosing LVSD in a primary care setting, with similar sensitivities and specificities. Due to the high NPV is useful to rule-out patients for echocardiography.

Albumin Binds COVID-19 Spike 1 Subunit and Predicts In-Hospital Survival of Infected Patients-Possible Alteration by Glucose.

(1) Background: This study aimed to analyze if the serum albumin levels of hospitalized SARS-CoV-2 (COVID-19) patients on admission could predict <30 days in-hospital all-cause mortality, and if glucose levels on admission affected this predictive ability. (2) Methods: A multicenter retrospective cohort of 1555 COVID-19-infected adult patients from public hospitals of the Madrid community were analyzed. (3) Results: Logistic regression analysis showed increased mortality for ages higher than 49 y. After adjusting for age, comorbidities and on-admission glucose levels, it was found that on-admission serum albumin ≥3.5 g/dL was significantly associated with reduced mortality (OR 0.48; 95%CI:0.36-0.62). There was an inverse concentration-dependent association between on-admission albumin levels and <30 days in-hospital all-cause mortality. However, when on-admission glucose levels were above 125 mg/dL, higher levels of serum albumin were needed to reach an association with survival. In vitro experiments showed that the spike protein S1 subunit of SARS-CoV-2 binds to native albumin. The binding ability of native albumin to the spike protein S1 subunit was decreased in the presence of an increasing concentration of glycated albumin. (4) Conclusions: On-admission serum albumin levels were inversely associated with <30 days in-hospital all-cause mortality. Native albumin binds the spike protein S1 subunit, suggesting that native albumin may act as a scavenger of the SARS-CoV-2 virus.

Noninvasive assessment of the right ventricular filling pressure gradient.

BACKGROUND: The physiological basis of right ventricular (RV) diastolic function remains incompletely studied in humans. The driving force responsible for RV filling, the pressure gradient along the RV inlet from the right atrium to the RV apex, has never been measured in the clinical setting. METHODS AND RESULTS: We validated a method for measuring the RV filling pressure difference (RVFPD) from color Doppler M-mode recordings in 12 pigs undergoing interventions on RV preload, afterload, and lusitropic states (error, -0.1+/-0.4 mm Hg compared with micromanometers; intraclass correlation coefficient, 0.88). Peak early RVFPD correlated directly with mean right atrial pressure and inversely with the time constant of RV relaxation. In 21 patients with dilated cardiomyopathy, the peak RVFPD was 1.0 mm Hg (95% CI, 0.8 to 1.2), significantly lower than in age-matched control subjects (1.4 mm Hg; 95% CI, 1.2 to 1.6). In another population of 19 young healthy volunteers, the peak RVFPD was 2.3 mm Hg (95% CI, 2.0 to 2.6), which was reduced by nitroglycerine and esmolol and was augmented by volume overload and atropine infusions. RVFPD was generated almost exclusively by inertial forces. CONCLUSIONS: For the first time, the RV driving filling force can be accurately measured noninvasively in the clinical setting, and the method is sensitive to detect the effects of preload, chronotropic, and lusitropic states. In patients with dilated cardiomyopathy, the RV filling force is markedly reduced, indicating severely impaired RV relaxation. These findings suggest that this is a useful tool for improving the clinical assessment of RV diastolic function.

Impact of image spatial, temporal, and velocity resolutions on cardiovascular indices derived from color-Doppler echocardiography.

Quantitative processing of color-Doppler echocardiographic images has substantially improved noninvasive assessment of cardiac physiology. Many indices are computed from the velocity fields derived either from color-Doppler tissue imaging (DTI), such as acceleration, strain and strain-rate, or from blood-flow color-Doppler, such as intracardiac pressure gradients (ICPG). All of these indices are dependent on the finite resolution of the ultrasound scanner. Therefore, we developed an image-dependent method for assessing the influence of temporal, spatial, and velocity resolutions, on cardiovascular parameters derived from velocity images. In order to focus our study on the spatial, temporal, and velocity resolutions of the digital image, we did not consider the effect of other sources of noise such as the interaction between ultrasound and tissue. A simple first-order Taylor's expansion was used to establish the functional relationship between the acquired image velocity and the calculated cardiac index. Resolutions were studied on: (a) myocardial acceleration, strain, and strain-rate from DTI, and (b) ICPG from blood-flow color-Doppler. The performance of Taylor's-based error bounds (TBEB) was demonstrated on simulated models and illustrated on clinical images. Velocity and temporal resolution were highly relevant for the accuracy of DTI-derived parameters and ICPGs. TBEB allow to assess the effects of ideal digital image resolution on quantitative cardiovascular indices derived from velocity measurements obtained by cardiac imaging techniques.

Doppler-derived ejection intraventricular pressure gradients provide a reliable assessment of left ventricular systolic chamber function.

BACKGROUND: Ejection intraventricular pressure gradients are caused by the systolic force developed by the left ventricle (LV). By postprocessing color Doppler M-mode (CDMM) images, we can measure noninvasively the ejection intraventricular pressure difference (EIVPD) between the LV apex and the outflow tract. This study was designed to assess the value of Doppler-derived EIVPDs as noninvasive indices of systolic chamber function. METHODS AND RESULTS: CDMM images and pressure-volume (conductance) signals were simultaneously acquired in 9 minipigs undergoing pharmacological interventions and acute ischemia. Inertial, convective, and total EIVPD curves were calculated from CDMM recordings. Peak EIVPD closely correlated with indices of systolic function based on the pressure-volume relationship: peak elastance (within-animal R=0.98; between-animals R=0.99), preload recruitable stroke work (within-animal R=0.81; between-animals R=0.86), and peak of the first derivative of pressure corrected for end-diastolic volume (within-animal R=0.88; between-animals R=0.91). The correlation of peak inertial EIVPD with these indices was also high (all R>0.75). Load dependence of EIVPDs was studied in another 5 animals in which consecutive beats obtained during load manipulation were analyzed. During caval occlusion (40% EDV reduction), dP/dtmax, ejection fraction, and stroke volume significantly changed, whereas peak EIVPD remained constant. Aortic occlusion (40% peak LV pressure increase) significantly modified dP/dtmax, ejection fraction, and stroke volume; a nearly significant trend toward decreasing peak EIVPD was observed (P=0.06), whereas inertial EIVPD was unchanged (P=0.6). EIVPD beat-to-beat and interobserver variabilities were 2+/-12% and 5+/-11%, respectively. CONCLUSIONS: Doppler-derived EIVPDs provide quantitative, reproducible, and relatively load-independent indices of global systolic chamber function that correlate closely with currently available reference methods.

A noninvasive method for assessing impaired diastolic suction in patients with dilated cardiomyopathy.

BACKGROUND: Diastolic suction is a major determinant of early left ventricular filling in animal experiments. However, suction remains incompletely characterized in the clinical setting. METHODS AND RESULTS: First, we validated a method for measuring the spatio-temporal distributions of diastolic intraventricular pressure gradients and differences (DIVPDs) by digital processing color Doppler M-mode recordings. In 4 pigs, the error of peak DIVPD was 0.0+/-0.2 mm Hg (intraclass correlation coefficient, 0.95) compared with micromanometry. Forty patients with dilated cardiomyopathy (DCM) and 20 healthy volunteers were studied at baseline and during dobutamine infusion. A positive DIVPD (toward the apex) originated during isovolumic relaxation, reaching its peak shortly after mitral valve opening. Peak DIVPD was less than half in patients with DCM than in control subjects (1.2+/-0.6 versus 2.5+/-0.8 mm Hg, P<0.001). Dobutamine increased DIVPD in control subjects by 44% (P<0.001) but only by 23% in patients with DCM (P=NS). DIVPDs were the consequence of 2 opposite forces: a driving force caused by local acceleration, and a reversed (opposed to filling) convective force that lowered the total DIVPD by more than one third. In turn, local acceleration correlated with E-wave velocity and ejection fraction, whereas convective deceleration correlated with E-wave velocity and ventriculo:annular disproportion. Convective deceleration was highest among patients showing a restrictive filling pattern. CONCLUSIONS: Patients with DCM show an abnormally low diastolic suction and a blunted capacity to recruit suction with stress. By raising the ventriculo:annular disproportion, chamber remodeling proportionally increases convective deceleration and adversely affects left ventricular filling. These previously unreported mechanisms of diastolic dysfunction can be studied by using Doppler echocardiography.

Dosimetric Characteristics of an EMF Delivery System Based on a Real-Time Impedance Measurement Device.

In this paper, the dosimetric characterization of an EMF exposure setup compatible with real-time impedance measurements of adherent biological cells is proposed. The EMF are directly delivered to the 16-well format plate used by the commercial xCELLigence apparatus. Experiments and numerical simulations were carried out for the dosimetric analysis. The reflection coefficient was less than -10 dB up to 180 MHz and this exposure system can be matched at higher frequencies up to 900 and 1800 MHz. The specific absorption rate (SAR) distribution within the wells containing the biological medium was calculated by numerical finite-difference time domain simulations and results were verified by temperature measurements at 13.56 MHz. Numerical SAR values were obtained at the microelectrode level where the biological cells were exposed to EMF including 13.56, 900, and 1800 MHz. At 13.56 MHz, the SAR values, within the cell layer and the 270-µL volume of medium, are 1.9e3 and 3.5 W/kg/incident mW, respectively.

Estimation of the end of ejection in aortic stenosis: an unreported source of error in the invasive assessment of severity.

BACKGROUND: All indices of aortic stenosis (AS) rely on measurements of mean transvalvular pressure gradient (DeltaP) and flow rate. Because the gradient is reversed during late ejection, the late systolic left ventricular (LV)-aortic pressure crossover may be an erroneous landmark of end-ejection. The aortic incisura should be a better reference to calculate indices of AS invasively. METHODS AND RESULTS: The accuracy of the pressure crossover and the incisura to define end-ejection was assessed in a chronic AS experimental model (9 dogs) with the use of an implantable flowmeter and Doppler echocardiography as reference. In 288 hemodynamic recordings analyzed (aortic valve area [AVA]: 0.74+/-0.46 cm2), ejection ended 37+/-29 ms after the pressure crossover but almost simultaneously with the incisura (2+/-17 ms). Pressure crossover error accounted for significant errors in the measurement of DeltaP (95% limits of agreement, +0 to +7 mm Hg) and AVA (-0.1 to +0.2 cm2). These errors were reduced to less than half with the use of the incisura to define end-ejection. Additionally, the agreement with Doppler-derived AS indices was best with use of the incisura. Pressure crossover error was maximal in situations of higher output, moderate orifice narrowing, higher arterial compliance, and lower vascular resistance. In 32 consecutive patients undergoing cardiac catheterization for AS, the pressure crossover induced a clinically important overestimation of the DeltaP from +22 to +50%. Errors in AVA estimation were considerably smaller (-2% to +6%) because of simultaneous and offsetting errors in the measurements of DeltaP and flow. CONCLUSIONS: The aortic incisura and not the second pressure crossover should be used to obtain invasive indices of AS.

Clinical efficacy of Doppler-echocardiographic indices of aortic valve stenosis: a comparative test-based analysis of outcome.

OBJECTIVES: This study was designed to assess which hemodynamic index best accounts for clinical severity of aortic stenosis (AS) and to analyze the value of low-dose dobutamine testing. BACKGROUND: Pressure gradient and valve area are suboptimal because they depend on flow rate, correlate poorly with symptoms, and provide limited prognostic information. Recently, new indices and low-dose inotropic stimulation have been introduced, but their clinical value remains uncertain. METHODS: A total of 307 consecutive patients with AS were included in an ambispective study design (71 +/- 12 years old; peak jet velocity: 3.7 +/- 1.1 m/s). Clinical and Doppler-echocardiographic data were obtained, as well as results of low-dose dobutamine infusion (47 patients). Using receiver-operator-characteristic curve analysis, we evaluated jet velocity, pressure gradient, valve area, resistance, stroke-work loss (SWL), and dobutamine-induced increase in area for predicting 1) symptomatic status at entry, 2) early (25% best discriminated clinical end points. Other independent predictors of prognosis were symptomatic status and left ventricular ejection fraction. Dobutamine testing added no value to baseline models. CONCLUSIONS: Non-flow-corrected indices show the highest clinical efficacy in aortic stenosis. Among these, SWL best predicts symptomatic status and outcome and therefore should be incorporated to aid patient management in unclear situations.

Noninvasive assessment of ejection intraventricular pressure gradients.

OBJECTIVES: The study was designed to validate in vivo a new method to measure ejection intraventricular pressure gradients (IVPGs) by processing color M-mode Doppler data and to assess the effects of inotropic interventions on IVPGs in the clinical setting. BACKGROUND: In the absence of obstruction, ejection IVPGs cannot be estimated by Doppler using the simplified Bernoulli equation. METHODS: High-fidelity micromanometers were placed in the left ventricle of eight minipigs, and synchronic Doppler images and pressure signals were obtained during different hemodynamic conditions. Twenty healthy volunteers and 20 dilated cardiomyopathy patients were studied at baseline and during esmolol, dobutamine, and atropine infusion (only dobutamine in patients). RESULTS: Excellent agreement was observed between micromanometer and Doppler methods for measuring instantaneous pressure differences among the apex, the mid-cavity, and the outflow tract (R(intraclass) = 0.98, 0.81, 0.76, and 0.98 for the peak, time-to-peak, peak reverse, and time-to-peak reverse values, respectively; n = 810 beats). Error of the noninvasive method was -0.05 +/- 0.25 mm Hg for the peak pressure difference. Parametrical images demonstrated that IVPGs originate mainly in the mid-ventricle and then propagate to the outflow tract. Both the magnitude and the temporal course of IVPGs were different among volunteers and patients. Inotropic interventions induced significant changes in the apex-outflow tract pressure differences in both populations, whereas atropine had no effect on IVPGs. CONCLUSIONS: For the first time, ejection IVPGs can be accurately visualized and measured by Doppler-echocardiography. Important aspects of the dynamic interaction among myocardial performance, load mechanics, and ejection dynamics can be assessed in the clinical setting using this method.

Intramyocardial analysis of regional systolic and diastolic function in ischemic heart disease with Doppler tissue imaging: role of the different myocardial layers.

BACKGROUND: Preliminary experimental data have shown a nonuniform distribution of myocardial velocities (MVs) across the myocardial wall in normal conditions. However, after ischemic damage to the myocardium, a different pattern of reduction in the myocardial layers has been reported. The aim of this study is to analyze the spatial distribution of MVs and the resultant myocardial velocity gradients (MVGs) during the systolic and diastolic time periods. Doppler tissue imaging (DTI) in color M-mode was used to evaluate 3 different myocardial layers (endocardium, mesocardium, and epicardium) and their changes as a result of ischemia. METHODS: Thirty-two consecutive patients were studied with DTI color M-mode: 18 patients with a history of previous or ongoing myocardial infarction and 14 healthy subjects. Postprocessing of images was accomplished with proprietary software. MV and MVG values of all layers along both systolic and diastolic time were calculated. For temporal analysis, systole was subdivided in 3 equal periods. Early- and late-diastolic times were also identified. RESULTS: In ischemic patients, the mean MV and maximum MV throughout systole decreased significantly in the endocardium and mesocardium, whereas only slightly in the epicardium. The mean MVG was less in ischemic patients (0.66 +/- 0.11 vs 0.23 +/- 0.15, P <.03). Temporal analysis showed a decrease in the maximal MV and MVG in all layers over the 3 systolic periods. This decrease was the more consistent in mesocardium. In diastole, there was a decrease in maximal MV in all layers, being more pronounced in endocardium and mesocardium. Diastolic mean MVG was shown to be different between control and ischemic groups (-0.2 +/- 0.05 vs -0.10 +/- 0.04, P <.06). A significant decrease of the maximal MV in endocardium and mesocardium was reported in the temporal analysis during early diastole. No change was reported in the epicardium. The MVG value also showed a significant decrease (-2.69 +/- 0.29 vs -1.59 +/- 0.89, P <.02). In ischemic patients in late diastole, the maximum MV was increased in all layers of the myocardium, and this increase was observed mainly in the endocardium. An increase in the MVG (-0.78 +/- 0.18 vs -1.47 +/- 0.85, P = NS) was also reported during late diastole. CONCLUSION: There is a nonuniform distribution of velocities in the different myocardial layers under normal conditions. This distribution of velocities undergoes a significant change in patients with ischemic myocardial damage. Intramyocardial wall motion analysis could have clinical applications in both the early detection of ischemia and myocardial viability.

In-vivo analysis of the instantaneous transvalvular pressure difference-flow relationship in aortic valve stenosis: implications of unsteady fluid-dynamics for the clinical assessment of disease severity.

BACKGROUND AND AIM OF THE STUDY: Because the hemodynamic basis of aortic valve area (AVA) has never been validated in vivo, several alternative indices have been proposed to quantify the severity of aortic stenosis (AS). This study was designed to assess the fluid-dynamics of aortic valve stenosis in order to clarify which index best accounts for disease severity. The diagnostic implications of reversed deltaP during ejection were also investigated. METHODS: Chronic valvular AS characterized by stiff leaflets without commissural fusion was created surgically in eight adult mongrel dogs; three additional animals were used as controls. At two-week intervals (three studies per dog), simultaneous micromanometer pressure and transit-time Q measurements were collected under different hemodynamic conditions. Instantaneous deltaP and Q signals were processed digitally and fitted to a modified form of the unsteady Bernoulli equation in which AS is characterized by effective valve area. RESULTS: An unsteady Bernoulli equation accurately predicted measured instantaneous AP values (R = 0.97+/-0.06), and a quadratic correlation was observed between instantaneously fitted and Gorlin-derived AVA. Additionally, deltaP < 0 mmHg during late ejection was observed in the majority of AS datasets, with a normalized time to deltaP reversal of 93+/-13% for AS animals versus 69+/-36% for controls (p <0.0005). Time to deltaP reversal inversely correlated with the Strouhal number (R = -0.77), and was responsible for an overestimation of mean systolic transvalvular deltaP and Q that resulted in a significant bias in the Gorlin method. Error was highest in moderate stenosis with low transvalvular output. CONCLUSION: Unsteady fluid-dynamics supports AVA over other measures of AS such as aortic valve resistance. However importantly, late-ejection reversal of deltaP precludes estimating the systolic ejection period from pressure tracings, and accounts for an additional source of error when AS is quantified invasively.

Tracking of regions-of-interest in myocardial contrast echocardiography.

Analysis of intramyocardial perfusion by contrast echocardiography provides quantitative parameters for the assessment of ischemic disease. This analysis can be achieved by applying an ultrasound (US) burst of high mechanical index to destroy contrast bubbles, measuring various myocardial refilling parameters from the time curves obtained from regions-of-interest (ROIs) within the myocardial wall. To obtain reliable intensity curves, the position of the ROIs must be tracked to compensate for the heart motion along the sequence. In this work, we studied the use of optical flow techniques for ROI repositioning. Two block-matching and one differential technique were evaluated for this purpose. Performance was measured by comparing the result of automatic tracking with results of ROI repositioning by a human expert. This evaluation was carried out on experimental data from animals as well as on sequences from clinical studies. Results are considered to be accurate enough for clinical purposes, and computation times may allow for a real-time processing if incorporated into a US scanner.

Assessment of normal and ischaemic myocardium by quantitative M-mode tissue Doppler imaging.

This paper presents a methodology and a software package developed to quantify M-mode tissue Doppler imaging (TDI), defining a number of quantitative parameters drawn from velocity and gradient curves obtained after segmenting the myocardial wall into anatomical layers. The independent clinical predictive value of these parameters to detect motion abnormalities in the presence of ischaemia was evaluated in a comparative study between a group of 17 healthy volunteers and 18 ischaemic patients. Factor analysis and stepwise logistic regression were used to assess the independent predictive value of these parameters in detecting abnormal contractility of the basal posterior segment. The statistical analysis performed has proved that any single parameter related to the gradient intensity, particularly the maximum gradient at the moment of the "e" wave, provides meaningful clinical information, achieving a rate of correct classification of 79.1% on the same data set used for the analysis. Adding additional parameters does not improve the diagnostic performance. Further testing with different settings (stress studies, other pathologies or segments) is warranted.

Stress Echocardiography in Aortic Stenosis: Insights into Valve Mechanics and Hemodynamics.

Stress interventions have been classically combined with cardiac catheterization recordings to understand the hemodynamic principles of valvular stenosis. Indices of aortic stenosis such as pressure gradient and valve area were based on simple hydraulic principles and have proved to be clinically useful for patient management during a number of decades. With the advent of Doppler echocardiography, these hemodynamic indices can be readily obtained noninvasively. Abundant evidence obtained using exercise and pharmacological stress echocardiography has demonstrated that the assumptions of classic hemodynamic models of aortic stenosis were wrong. Consequently, it is recognized that conventional indices may be misleading indicators of aortic stenosis significance in particular clinical situations. To improve diagnostic accuracy, several alternative hemodynamic models have been developed in the past few years, including valve resistance and left ventricular stroke work loss, among others. Nevertheless, these more-accurate indices should be obtainable noninvasively and need to demonstrate greater diagnostic and prognostic power than conventional indices; preliminary data suggest such superiority. Stress echocardiography is well established as the tool of choice for testing hypothesis and physical models of cardiac valve function. Although the final role of alternative indices is not yet well established, the new insights into valvular hemodynamics provided by this technique may change the clinical assessment of aortic stenosis.

[Image techniques for the evaluation and clinical decision making of patients with stroke]. / Utilidad de las técnicas de imagen en la valoración etiológica y toma de decisiones en el paciente con ictus.

The clinical relevance of cardiac embolism a potential cause of stroke is progressively increasing, mainly due to the recent progress in diagnostic imaging. In the present paper, we update and review the state of the art of the different etiologies currently accepted of a cardiac source of stroke. Furthermore, we review the clinical role of different image techniques, emphasizing the doubts and realities of each particular approximation.