Rapid Screening for Subclinical Atherosclerosis by Carotid Ultrasound Examination: The HAPPY (Heart Attack Prevention Program for You) Substudy.

BACKGROUND: Cardiovascular disease (CVD)-related death rates have been escalating in emerging economies such as India. A strategy to initiate prophylactic medical intervention by direct identification of subclinical atherosclerotic burden may be appropriate in rural populations where assessment based on traditional risk factors is not available. OBJECTIVES: This study sought to investigate the feasibility of performing rapid automated carotid ultrasound studies in a rural setting and to measure the prevalence of carotid plaques and age-specific distribution of carotid intima-media thickness (IMT) as an index of subclinical atherosclerosis. METHODS: Screening of the extracranial carotid system with automated B-mode ultrasound was performed along with health questionnaire assessments in 771 asymptomatic volunteers (ages 40 ± 14 years; 626 men and 145 women) with no known CVD. Measurements of IMT were recorded as the mean of 24 spatial measurements performed over a 1-cm region in the far wall of the common carotid artery at end diastole; the prevalence of the plaque (focal IMT >1.5 mm) was determined. RESULTS: A total of 69 (8.9%) subjects had atherosclerotic plaques. Of these, 16 (2.1%) exhibited bilateral plaques, 28 (3.6%) left carotid plaque only, and 25 (3.2%) had right carotid plaques. Patients even under 50 years showed a high prevalence of carotid plaques (7%), which increased with age (25% and 35% for 51 to 70 and >70 years, respectively). Only 3 (4.3%) participants with plaques were former smokers. Global mean IMT was 0.55 ± 0.13 mm and correlated with age for both left and right carotid arteries (r = 0.61 and 0.60, p < 0.001 for both) in male as well as female subjects (r = 0.70 and 0.67, p < 0.001 for both), respectively. CONCLUSIONS: Rapid community screening for subclinical atherosclerosis is feasible with automated carotid ultrasound examination and may be beneficial in rural communities of industrializing nations where traditional CVD risk factor data are not yet readily available.

Automated border detection for assessing the mechanical properties of the carotid arteries: comparison with carotid intima-media thickness.

BACKGROUND: Although carotid intima-media thickness (CIMT) assesses the structural properties of the carotid artery, it does not assess the mechanical properties of the vessel. METHODS: The carotid arteries of 71 adult patients were evaluated with CIMT, and automated border detection computed vessel stiffness, compliance, elasticity, and distensibility. RESULTS: CIMT and mechanical properties were differentially affected by traditional cardiac risk factors, with age dominating for CIMT, and age, diabetes, and smoking dominating for mechanical variables. There was a moderate linear correlation between CIMT and the distensibility coefficient (r = -0.54), but there were weak associations with other parameters of dynamic vessel function. When patients were separated into risk groups, the mechanical vascular parameters' classification frequently differed from the CIMT classification. This was particularly notable for patients with intermediate CIMT values, who were reclassified as low or high risk by mechanical parameters 45% of the time. CONCLUSION: We found that it is feasible to assess the cross-sectional area of the carotid artery using automatic border detection, which allows a novel method of determining carotid mechanical properties. These functional characteristics are often discordant with CIMT, suggesting that mechanical properties may be an important adjunct to the CIMT when evaluating the carotid artery.

Semi-automated analysis of dynamic changes in myocardial contrast from real-time three-dimensional echocardiographic images as a basis for volumetric quantification of myocardial perfusion.

AIMS: Despite the potential of real-time three-dimensional (3D) echocardiography (RT3DE) to assess myocardial perfusion, there is no quantification method available for perfusion analysis from RT3DE images. Such method would require 3D regions of interest (ROI) to be defined and adjusted frame-by-frame to compensate for cardiac translation and deformation. Our aims were to develop and test a technique for automated identification of 3D myocardial ROI suitable for translation-free quantification of myocardial videointensity over time, MVI(t), from contrast-enhanced RT3DE images. METHODS AND RESULTS: Twelve transthoracic RT3DE (Philips) data sets obtained in pigs during transition from no contrast to steady-state enhancement (Definity) were analysed using custom software. Analysis included: (i) semi-automated detection of left ventricular endo- and epicardial surfaces using level-set techniques in one frame to define a 3D myocardial ROI, (ii) rigid 3D registration to reduce translation and rotation, (iii) elastic 3D registration to compensate for deformation, and (iv) quantification of MVI(t) in the 3D ROI from the registered and non-registered data sets to assess the effectiveness of registration. For each MVI(t) curve we computed % variability during steady-state enhancement (100 x SD/mean) and goodness of fit (r2) to the indicator dilution equation MVI(t) = A[1-exp(-betat)]. Analysis of myocardial contrast throughout contrast inflow was feasible in all data sets. Three-dimensional registration improved MVI(t) curves in terms of both % variability (2.8 +/- 1.8 to 1.5 +/- 0.9%; P < 0.05) and goodness of fit (r2 from 0.79 +/- 0.2 to 0.90 +/- 0.1; P < 0.05). CONCLUSION: This is the first study to describe a new technique for semi-automated volumetric quantification of myocardial contrast from RT3DE images that includes registration and thus provides the basis for 3D measurement of myocardial perfusion.

Use of carotid intima-media thickness to identify patients with ischemic stroke and transient ischemic attack with low yield of cardiovascular sources of embolus on transesophageal echocardiography.

BACKGROUND AND PURPOSE: Carotid intima-media thickness (CIMT) is associated with systemic atherosclerosis and cardioembolic conditions and predicts the risk of recurrent strokes. We sought to establish the relationship between CIMT and cardiovascular sources of embolus (CSE) on transesophageal echocardiography (TEE) and hypothesized that a noninvasive strategy of CIMT assessment and transthoracic echocardiography bubble study would identify patients with ischemic stroke or transient ischemic attack in whom TEE would provide little incremental diagnostic yield. METHODS: In 180 patients with ischemic stroke or transient ischemic attack of undetermined origin referred for TEE, we prospectively performed CIMT measurement/plaque screen (Phase 1, n=96) or CIMT measurement/plaque screen and transthoracic echocardiography bubble study (Phase 2, n=84) before TEE. Phase 1 results were used to construct receiver operating characteristic curves to demonstrate the ability of CIMT to detect CSE on TEE and to identify the optimal CIMT cutoff value for prospective strategy testing (Phase 2). RESULTS: In Phase 1, CIMT was found to correlate with TEE markers of aortic atherosclerosis, including complex aortic plaques, and combined CSE. The optimal CIMT cutoff for detection of CSE on TEE was 0.78 mm. In Phase 2, a positive noninvasive strategy test (CIMT >or=0.78 mm, +carotid plaque, and/or a positive transthoracic echocardiography bubble study) was present in 61%. The prevalence of CSE on TEE was significantly higher among those with a positive compared with a negative noninvasive strategy test (65% versus 9%, P<0.001), and this strategy had a sensitivity of 92% and a negative predictive value of 91% for the detection of any CSE on TEE. CONCLUSIONS: In patients with stroke or transient ischemic attack of undetermined origin, a noninvasive strategy of CIMT assessment/plaque screen and transthoracic echocardiography bubble study can identify patients in whom further invasive evaluation with TEE will be of low diagnostic yield.

Comparison of the frequency of abnormal cardiac findings by echocardiography in patients with and without peripheral arterial disease.

Peripheral arterial disease (PAD) diagnosed by ankle-brachial index (ABI) evaluation is associated with a high cardiovascular mortality rate. Transthoracic echocardiography (TTE) allows identification of left ventricular (LV) dysfunction and other cardiac findings associated with an increased cardiovascular mortality rate, for which treatments to alter prognosis are available. We sought to determine the prevalence of important TTE abnormalities in outpatients with symptomatic PAD by performing screening TEE. Outpatients without previous echocardiography who had been referred for ABI evaluation for suspected PAD underwent prospective screening TTE. The primary end points were LV dysfunction (LV ejection fraction 0.9, n = 84), and PAD was found to be an independent predictor of LV dysfunction (odds ratio 2.8, 95% confidence interval 1.2 to 6.4) and composite clinically important echocardiographic findings (3.2 95% confidence interval 1.5 to 7.1, p <0.01). In conclusion, outpatients with symptomatic PAD have a high prevalence of clinically important TTE abnormalities, including LV dysfunction, and PAD is an independent predictor of an abnormal echocardiogram.

Use of real-time 3-dimensional transthoracic echocardiography in the evaluation of mitral valve disease.

Three-dimensional (3D) echocardiography (3DE) provides unique orientations of the mitral valve (MV) not obtainable by routine 2-dimensional echocardiography. However, this modality has not been adopted in routine clinical practice because of its cumbersome and time-consuming process. The recent introduction of a full matrix-array transducer has enabled online real-time 3DE (RT3DE) and rendering. This study was designed to: (1) determine the clinical use of RT3DE in patients with MV pathology and in a control group selected for their good acoustic windows (protocol I); and (2) to investigate the feasibility of imaging the MV apparatus in a large group of consecutively imaged patients to determine the acoustic window or perspective from which the MV leaflets, commissures, and orifice are best visualized (protocol II). In protocol I, 65 patients were selected based on MV pathology and good 2-dimensional echocardiography image quality. Protocol II included 150 patients who were consecutively imaged using RT3DE. Images were viewed online (protocol I) and offline on a digital review station (protocol II). RT3DE visualization of the MV apparatus was graded based on the percentage of leaflet dropout and definition. In protocol I, 78% of patients had adequate 3D MV reconstructions with complete visualization of the anterior mitral leaflet (AML) in 84% versus the posterior mitral leaflet (PML) in 77%. The mitral leaflets, commissures, and MV orifice were well seen in 98%; however, the submitral apparatus was only observed in 76% of the patients. RT3DE: (1) correctly identified the prolapsed/flailed scallop in 6 of 8 patients; (2) obtained en face orientation of the MV orifice in 9 of 11 patients with mitral stenosis, allowing accurate measurements of the orifice area and evaluation of the immediate effects of balloon mitral valvuloplasty; and (3) allowed postoperative evaluation of MV repair and the integrity of the struts of a bioprosthetic leaflet. In protocol II, 70% of patients had adequate RT3DE with complete visualization of the AML noted in 55% versus 51% for PML. The mitral leaflets, commissures, and MV orifice were observed in 69%. Irrespective of acquisition window, the AML was best seen from a ventricular perspective. In contrast, the PML was optimally examined from a parasternal window. Both the medial and lateral commissures were equally assessed from either imaging window. In conclusion, RT3DE of the MV is feasible in a large majority of patients. Using different MV acquisitions RT3DE provides important clinical information such as: (1) identification of a prolapsed/flail scallop; (2) measurement of stenotic valve areas; (3) evaluation of MV leaflet integrity postrepair; and (4) identification of a MV perforation. In general the AML is better visualized than the PML. The parasternal window is the optimal approach to visualize both AML and PMLs.

Imaging and quantification of myocardial perfusion using real-time three-dimensional echocardiography.

OBJECTIVES: We tested the feasibility of real-time three-dimensional echocardiographic (RT3DE) perfusion imaging and developed and validated an algorithm for volumetric analysis of myocardial contrast inflow. The study included three protocols wherein perfusion was measured: 1) in an ex-vivo model of controlled global coronary flow, 2) in an in-vivo model during regional perfusion variations, and 3) in humans during pharmacologically induced hyperemia. BACKGROUND: The RT3DE technology offers an opportunity for myocardial perfusion imaging without multi-slice reconstruction and repeated contrast maneuvers. METHODS: Electrocardiographically triggered harmonic RT3DE datasets were acquired (Philips 7500) while infusion of Definity was initiated and reached a steady state. Protocol 1 was performed in nine isolated rabbit hearts and included three coronary flow levels. In protocol 2, changes in regional perfusion caused by partial left anterior descending artery occlusion were measured in five pigs. In protocol 3, adenosine-induced changes in perfusion were measured in eight normal volunteers. Myocardial video-intensity (MVI) was measured over time in three-dimensional (3D) slices to calculate peak contrast inflow rate (PCIR). In pigs, PCIR was measured on a regional basis and validated against microspheres. RESULTS: The RT3DE imaging allowed selection of slices for perfusion analysis in rabbit hearts, pigs, and humans. Administration of contrast resulted in clearly visible and quantifiable changes in MVI. In rabbits, The PCIR progressively decreased with coronary flow (p < 0.0001). In pigs, coronary occlusion caused a 59 +/- 26% decrease in PCIR exclusively in the left anterior descending artery territory (p < 0.05) in agreement with microspheres. In humans, adenosine increased PCIR to 198 +/- 57% of baseline (p < 0.05). CONCLUSIONS: Contrast-enhanced RT3DE imaging provides the basis for volumetric imaging and quantification of myocardial perfusion.

Evaluation of left ventricular systolic function using automated angle-independent motion tracking of mitral annular displacement.

Determination of ejection fraction (EF) in clinical practice typically involves manual tracing of endocardial borders. This method is time-intensive and highly dependent on image quality. Mitral annular displacement (MAD) has been shown to correlate well with EF. Previously, this method involved tedious analysis of M-mode tracings. We developed and studied a new technique that is ultrasound beam angle-independent for automated detection of MAD, based on a tissue tracking algorithm. A regression formula was derived in a study group to predict EF from MAD measurements and tested prospectively in a separate group of patients. We found that our technique provides accurate, ultra-fast estimation of EF with lower inter- and intraobserver variability when compared with manually traced biplane EF.

Quantitative echocardiographic evaluation of myocardial perfusion using interrupted contrast infusion technique: in vivo validation studies and feasibility in human beings.

BACKGROUND: We recently developed a new approach for contrast echocardiographic quantification of myocardial perfusion, based on brief interruptions of contrast infusion, which was designed to overcome the limitations of existing techniques. In this study, our technique was initially validated in a series of animal experiments designed to detect regional perfusion variations in vivo. Subsequently, clinical feasibility of perfusion measurements was tested. METHODS: Regional perfusion was measured transthoracically in 6 anesthetized pigs during baseline, partial left anterior descending coronary artery occlusion, and reperfusion, and validated with fluorescent microspheres. Adenosine-induced changes in perfusion were measured in 8 healthy volunteers. In both protocols, imaging was optimized during contrast infusion (Definity). Infusion was interrupted to allow contrast clearance and images were acquired during subsequent contrast inflow. Myocardial videointensity was measured over time and peak contrast inflow rate was calculated. RESULTS: In pigs, partial coronary occlusion resulted in a 47 +/- 23% decrease in peak contrast inflow rate in the left anterior descending coronary artery perfusion territory (P < .05), which was reversed during reperfusion, without concomitant decrease in other perfusion territories. These changes were in agreement with microspheres. In human beings, adenosine increased peak contrast inflow rate to 278 +/- 123% of baseline (P < .05). CONCLUSION: The interruption of contrast infusion technique is a sensitive tool for accurate quantification of myocardial perfusion, which may constitute an alternative to currently used techniques.

Interrupted infusion of echocardiographic contrast as a basis for accurate measurement of myocardial perfusion: ex vivo validation and analysis procedures.

BACKGROUND: Echocardiographic quantification of myocardial perfusion is based on analysis of contrast replenishment after destructive high-energy ultrasound impulses (flash-echo). This technique is limited by nonuniform microbubble destruction and the dependency on exponential fitting of a small number of noisy time points. We hypothesized that brief interruptions of contrast infusion (ICI) would result in uniform contrast clearance followed by slow replenishment and, thus, would allow analysis from multiple data points without exponential fitting. METHODS: Electrocardiographic-triggered images were acquired in 14 isolated rabbit hearts (Langendorff) at 3 levels of coronary flow (baseline, 50%, and 15%) during contrast infusion (Definity) with flash-echo and with a 20-second infusion interruption. Myocardial videointensity was measured over time from flash-echo sequences, from which characteristic constant beta was calculated using an exponential fit. Peak contrast inflow rate was calculated from ICI data using analysis of local time derivatives. Computer simulations were used to investigate the effects of noise on the accuracy of peak contrast inflow rate and beta calculations. RESULTS: ICI resulted in uniform contrast clearance and baseline replenishment times of 15 to 25 cardiac cycles. Calculated peak contrast inflow rate followed the changes in coronary flow in all hearts at both levels of reduced flow (P < .05) and had a low intermeasurement variability of 7 +/- 6%. With flash-echo, contrast clearance was less uniform and baseline replenishment times were only 4 to 6 cardiac cycles. beta Decreased significantly only at 15% flow, and had intermeasurement variability of 42 +/- 33%. Computer simulations showed that measurement errors in both perfusion indices increased with noise, but beta had larger errors at higher rates of contrast inflow. CONCLUSION: ICI provides the basis for accurate and reproducible quantification of myocardial perfusion using fast and robust numeric analysis, and may constitute an alternative to the currently used techniques.

Accuracy of mitral valve area measurements using transthoracic rapid freehand 3-dimensional scanning: comparison with noninvasive and invasive methods.

OBJECTIVE: The feasibility and accuracy of direct transthoracic 3-dimensional (3D) mitral valve area (MVA) measurements obtained using freehand scanning was investigated in patients with mitral stenosis. METHODS: A total of 30 patients (26 women, 4 men; aged 55 +/- 13 years) underwent a 2-dimensional (2D) and Doppler study 1 hour before percutaneous balloon mitral valvuloplasty. Transthoracic freehand data were acquired using a magnetic receiver attached to a broadband transducer, gated to electrocardiography and respiration. Volumetric MVA measurements from the left ventricle and left atrium were obtained and compared with MVA measurements derived from 2D planimetry, pressure half-time, and proximal isovelocity surface area. Invasive Gorlin MVA measurements were the gold standard for comparison. RESULTS: In all, 29 patients (97%) had 3D data allowing MVA measurements. Direct 3D measurements from the left ventricle had the least bias (0.06 +/- 0.19 cm(2)) and tightest limits of agreement (-0.44 to 0.32) compared with left atrium measurements (0.17 +/- 0.25 cm(2) and -0.67 to 0.33, respectively). The proximal isovelocity surface area method (bias: 0.09 +/- 0.34 cm(2)) was the most accurate of all 2D methods followed by pressure half-time (0.17 +/- 0.36 cm(2)) and planimetry (0.21 +/- 0.29 cm(2)). CONCLUSION: Direct 3D MVA measurements from the left ventricle using transthoracic freehand scanning are more accurate than traditional 2D methods.

Biplane stress echocardiography using a prototype matrix-array transducer.

BACKGROUND: Rapid image acquisition after cessation of exercise is essential for accurate stress echocardiography. Recently, a prototype matrix-array transducer has been developed that allows simultaneous acquisition of 2 imaging planes (biplane [BP] imaging). METHODS: In all, 19 healthy volunteers underwent 2 separate stress echocardiographic studies. Images were acquired in traditional 2-dimensional or BP format pre-exercise and postexercise. RESULTS: Total image acquisition time for 2-dimensional stress echocardiography was 38 +/- 8 seconds versus 29 +/- 8 seconds for BP imaging (P <.05). Heart rates were acquired closer to age-predicted maximum with BP imaging in the apical 3- and 2-chamber and parasternal long- and short-axis views (82%, 75%, 70%, 70% for BP vs 76%, 72%, 68%, 66% for 2-dimensional, respectively). CONCLUSION: BP imaging using a recently developed matrix-array probe allows more rapid imaging postexercise, resulting in acquisition of poststress images at higher heart rates without compromising image quality.

Dynamic three-dimensional color flow Doppler: an improved technique for the assessment of mitral regurgitation.

BACKGROUND: Prior studies have reconstructed mitral regurgitant flow in three dimensions displaying gray scale renditions of the jets, which were difficult to differentiate from surrounding cardiac structures. Recently, a color-coded display of three-dimensional (3D) regurgitant flow has been developed. However, this display was unable to integrate cardiac anatomy, thereby losing spatial information, which made it difficult to determine the jet origin and its spatial trajectory. To overcome this limitation, an improved method of 3D color reconstruction of regurgitant jets obtained from color flow Doppler using a transesophageal approach was developed to allow the combined display of both color flow and gray scale information. OBJECTIVES: To demonstrate the feasibility of 3D reconstruction of regurgitant mitral flow jets using an improved method of color encoding digital data acquired by transesophageal echocardiography (TEE). METHODS: We studied 46 patients undergoing a clinically indicated TEE study. All subjects had mitral regurgitation detected on a previous transthoracic study. Atrial fibrillation or poor image quality were not used as exclusion criteria. The 3D study was performed using a commercial ultrasound imaging system with a TEE probe (Sonos 5500, Agilent Technologies). A rotational mode of acquisition was used to collect two-dimensional (2D) color flow images at 3-degree intervals over 180 degrees. Images were processed off line using the Echo-View Software (TomTec Imaging Systems). Volume-rendered 3D color flow jets were displayed along with gray scale information of the adjacent cardiac structures. RESULTS: Mitral regurgitant flow, displayed in left atrial and two longitudinal orientations, was successfully reconstructed in all patients. The time for acquisition, post-processing, and rendering ranged between 10 and 15 minutes. There were 28 centrally directed jets and 15 eccentric lesions. Eight patients in the study had periprosthetic mitral regurgitant flow. CONCLUSIONS: Three-dimensional imaging of mitral regurgitant jets is feasible in the majority of patients. This improved technique provides additional information to that obtained from the 2D examination. Particularly, in patients with paravalvular leaks 3D color flow Doppler provides information on the origin and the extent of the dehiscence, as well as insight into the jet direction. In addition, in patients with eccentric mitral regurgitation, this new modality overcomes the inherent limitations of 2D echo Doppler by depicting the full extent of the jet trajectory.