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Objectives: The association of transaortic flow rate (FR) with outcomes was tested in 1,661 patients with aortic valve stenosis (AS) in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study., Background: Low transaortic flow may complicate grading of AS. However, the association of lower transaortic FR with adverse outcomes has not been reported., Methods: Transaortic FR was calculated from Doppler-derived stroke volume in milliliters divided by systolic ejection time in seconds and considered low if <200 ml/s. The association of transaortic FR with cardiovascular and all-cause mortality during 4.3-year follow-up was tested in time-varying Cox regression models run with aortic valve replacement as competing risk and reported as hazard ratio (HR) and 95% confidence interval (CI)., Results: Low transaortic FR was found in 21% of patients at baseline. Patients with low transaortic FR were older, had lower systemic arterial compliance and left ventricular mass, and included more women and patients with inconsistently graded severe AS and low stroke volume index (<35 ml/m 2 ) (p < 0.01 for all). Low in-study transaortic FR was associated with higher rates of cardiovascular and all-cause mortality both in unadjusted analyses (HR: 2.56 [95% CI: 1.62 to 4.04]; and HR: 1.93 [95% CI: 1.35 to 2.75], respectively; p < 0.001 for both) and after adjustment for age, sex, randomized study treatment, hypertension, stroke volume index <35 ml/m 2 , LV mass, and mean aortic gradient (HR: 2.79 [95% CI: 1.65 to 4.73]; and HR: 1.90 [95% CI: 1.27 to 2.84], respectively; p < 0.01 for both)., Conclusions: In patients with AS without known cardiovascular disease or diabetes, low transaortic FR was independently associated with higher rates of cardiovascular and all-cause mortality. (An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis (Narrowing of the Major Blood Vessel of the Heart) (MK-0653A-043 AM4); NCT00092677)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Carotid intima-media thickness (IMT) and plaque are recognized markers of increased risk for cerebrovascular events. Accurate visualization of the IMT and plaques is dependent upon image quality. Ultrasound contrast agents improve image quality during echocardiography-this study assessed whether contrast-enhanced ultrasound (CEUS) improves carotid IMT visualization and plaque detection in an asymptomatic population., Methods & Results: Individuals free from known cardiovascular disease, enrolled in a community study, underwent B-mode and CEUS carotid imaging. Each carotid artery was divided into 10 segments (far and near walls of the proximal, mid and distal segments of the common carotid artery, the carotid bulb, and internal carotid artery). Visualization of the IMT complex and plaque assessments was made during both B-mode and CEUS imaging for all enrolled subjects, a total of 175 individuals (mean age 65±9 years). Visualization of the IMT was significantly improved during CEUS compared with B-mode imaging, in both near and far walls of the carotid arteries (% IMT visualization during B-mode vs CEUS imaging: 61% vs 94% and 66% vs 95% for right and left carotid arteries, respectively, P<.001 for both). Additionally, a greater number of plaques were detected during CEUS imaging compared with B-mode imaging (367 plaques vs 350 plaques, P=.02)., Conclusion: Contrast-enhanced ultrasound improves visualization of the intima-media complex, in both near and far walls, of the common and internal carotid arteries and permits greater detection of carotid plaques. Further studies are required to determine whether there is incremental clinical and prognostic benefit related to superior plaque detection by CEUS., (© 2017, Wiley Periodicals, Inc.)

Studies have reported that intraplaque neovascularisation (IPN) is closely correlated with plaque vulnerability. In this study, a new image processing approach, differential intensity projection (DIP), was developed to visualise and quantify IPN in contrast-enhanced non-linear ultrasound image sequences of carotid arteries. DIP used the difference between the local temporal maximum and the local temporal average signals to identify bubbles against tissue non-linear artefact and noise. The total absolute and relative areas occupied by bubbles within each plaque were calculated to quantify IPN. In vitro measurements on a laboratory phantom were made, followed by in vivo measurements in which 24 contrast-enhanced non-linear ultrasound image sequences of carotid arteries from 48 patients were selected and motion corrected. The results using DIP were compared with those obtained by maximum intensity projection (MIP) and visual assessment. The results indicated that DIP can significantly reduce non-linear propagation tissue artefacts and is much more specific in detecting bubble signals than MIP, being able to reveal microbubble signals that are buried in tissue artefacts in the corresponding MIP image. A good correlation was found between microvascular area (MVA) (r = 0.83, p < 0.001)/microvascular density (r = 0.77, p < 0.001) obtained using DIP and the corresponding expert visual grades, comparing favourably to r = 0.26 and 0.23 obtained using MIP on the same data. In conclusion, the proposed method exhibits great potential in quantification of IPN in contrast-enhanced ultrasound images of carotid arteries., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: Abnormal proliferation of adventitial vasa vasorum (vv) occurs early at sites of atherosclerosis and is thought to be an early biomarker of vascular damage. Contrast-enhanced ultrasound (CEUS) can detect this process. Its usefulness in irradiated arteries as a measure of accelerated atherosclerosis is unknown. This study investigates contrast intensity in carotid adventitia as an early marker of radiation-induced damage in head and neck cancer (HNC) patients., Materials/methods: Patients with HNC treated with a wedged-pair and matched neck technique or hemi-neck radiotherapy (RT) (unirradiated side as control) at least 2years previously were included. Patients had been prescribed a dose of at least 50Gy to the neck. CEUS was performed on both carotid arteries and a region of interest was selected in the adventitia of the far wall of both left and right distal common carotid arteries. Novel quantification software was used to compare the average intensity per pixel between irradiated and unirradiated arteries., Results: 48 patients (34 males) with median age of 59.2years (interquartile range (IQR) 49.2-64.2) were included. The mean maximum point dose to the irradiated artery was 61.2Gy (IQR 52.6-61.8) and 1.1Gy (IQR 1.0-1.8Gy) to the unirradiated side. The median interval from RT was 59.4months (IQR 41-88.7). There was a significant difference in the mean (SD) contrast intensity per pixel on the irradiated side (1.1 (0.4)) versus 0.96 (0.34) on the unirradiated side (p=0.01). After attenuation correction, the difference in mean contrast intensity per pixel was still significant (1.4 (0.58) versus 1.2 (0.47) (p=0.02). Previous surgery or chemotherapy had no effect on the difference in contrast intensity between the 2 sides of the neck. Mean intensity per pixel did not correlate to traditional risk prediction models (carotid intima-medial thickness, QSTROKE score)., Conclusions: Proliferation of vv is demonstrated by increased contrast intensity in irradiated carotid arteries. This may be a useful, independent biomarker of radiation-induced carotid atherosclerosis when used as a tool to quantify neovascularization., (Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Primary radical radiotherapy (RT) for head and neck cancer (HNC) often results in significant radiation dose to the carotid arteries., Aim: We assessed whether HNC patients are at increased risk of a cerebrovascular event primarily due to RT or other risk factors for atherosclerosis by (i) risk-stratifying patients according to validated QRISK-2 and QSTROKE scores and (ii) comparing the prevalence of carotid artery stenosis (CAS) in irradiated and unirradiated carotid arteries., Design: HNC patients treated with an RT dose >50 Gy to one side of the neck ≥2 years previously were included., Methods: QRISK-2 (2014) and Q-STROKE (2014) scores were calculated. We compared the prevalence of CAS in segments of the common carotid artery on the irradiated and unirradiated sides of the neck., Results: Fifty patients (median age of 58 years (interquartile range (IQR) 50-62)) were included. The median QRISK-2 score was 10% (IQR 4.4-15%) and the median QSTROKE score was 3.4% (IQR 1.4-5.3%). For both scores, no patient was classified as high risk. Thirty-eight patients (76%) had CAS in one or both arteries. There was a significant difference in the number of irradiated arteries with stenosis (N = 37) compared with unirradiated arteries (N = 16) (P < 0.0001). There were more plaques on the irradiated artery compared with the unirradiated side - 64/87 (73.6%) versus 23/87 (26.4%), respectively (P < 0.001). , Conclusions: Traditional vascular risk factors do not play a role in radiation-induced carotid atherosclerosis. Clinicians should be aware that traditional risk prediction models may under-estimate stroke risk in these patients., (© The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of this study was to determine the effect of radiotherapy (RT) on intraplaque neovascularization (IPN) in human carotid arteries., Background: Exposure of the carotid arteries to RT during treatment for head and neck cancer is associated with increased risk for stroke. However, the effect of RT on IPN, a precursor to intraplaque hemorrhage and thus associated with plaque vulnerability, is unknown., Methods: In this cross-sectional study, patients who had undergone unilateral RT for head and neck cancer ≥2 years previously underwent B-mode and contrast-enhanced ultrasound of both RT-side and non-RT-side carotid arteries. Presence of IPN during contrast-enhanced ultrasound was judged semiquantitatively as grade 0 (absent), grade 1 (present but limited to plaque base), or grade 2 (extensive and noted within plaque body)., Results: Of 49 patients studied, 38 (78%) had plaques. The number of plaques was significantly greater in the RT than the non-RT arteries. Overall, 48 of 64 RT-side plaques (75%) had IPN compared with 9 of 23 non-RT-side (39%) plaques (p = 0.002). Among patients with plaques, IPN was present in 81% of patients with RT-side plaques and 41% of patients with non-RT-side plaques (p = 0.004). Grade 0 IPN was significantly more common in patients with non-RT-side plaques (25% vs. 61%; p = 0.002), whereas grade 2 plaques were more common on the RT side (31% vs. 9%; p = 0.03). The only clinical variable that predicted the presence or absence of IPN was RT laterality., Conclusions: This is the first study in humans to reveal a significant association between RT and the presence and extent of IPN. This may provide insights into the mechanisms underlying the increased stroke risk among survivors of head and neck cancer treated by RT., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Arterial stiffness is thought to be a precursor to atherosclerosis. Conventional arterial stiffness parameters as potential biomarkers of radiation-induced damage were investigated. Patients with head and neck cancer treated with radiotherapy ≥2 years previously to one side of the neck were included. The unirradiated side was the internal control. Beta stiffness index (B) and elastic modulus (Ep) were used to assess arterial stiffness and were measured in proximal, mid, and distal common carotid artery (CCA) and compared with the corresponding unirradiated segments. Fifty patients (68% male; median age 58 years; interquartile range 50-62) were included. Mean ± standard deviation maximum doses to irradiated and unirradiated arteries were 53 ± 13 and 1.9 ± 3.7 Gy, respectively. Differences in B were not significant. Significant differences in Ep were demonstrated-proximal CCA: 1301 ± 1223 versus 801 ± 492 (P < .0001), mid CCA: 1064 ± 818 versus 935.5 ± 793 (P < .0001), and distal CCA: 1267 ± 1084 versus 775.3 ± 551.9 (P < .0001). Surgery had no impact on arterial stiffness. Arterial stiffness is increased in irradiated arteries, in keeping with radiation-induced damage. Prospective data may show an association between arterial stiffness and atherosclerosis in this setting., (© The Author(s) 2015.)

Purpose: Arterial thickening is a precursor to atherosclerosis. Carotid intima-medial thickness (CIMT), a measure of arterial thickening, is a validated surrogate for prediction of cerebrovascular events. This study investigates CIMT as an early marker of radiation-induced carotid artery damage., Materials/methods: Head and neck cancer patients treated with radiotherapy (RT) (minimum dose of 50 Gy) to one side of the neck (unirradiated side as control) at least 2 years previously were included. CIMT was measured in 4 arterial segments: proximal, mid, distal common carotid artery (CCA), and bifurcation and were compared to corresponding unirradiated segments. CIMT measurements >75th percentile of a reference population were considered abnormal and at increased cerebrovascular risk., Results: 50 patients (34 males) with a median age of 58 years (interquartile range (IQR) 50-62) were included. The mean maximum dose to the irradiated and unirradiated artery was 53 Gy (standard deviation (SD) 13 Gy) and 1.9 Gy (SD 3.7 Gy), respectively. Mean CIMT was significantly greater in irradiated versus unirradiated arteries: proximal CCA (0.76 mm ± 0.15 vs 0.68 mm ± 0.14 (p<0.0001), mid CCA (0.74 mm ± 0.2 vs 0.68 mm ± 0.16 (p=0.01), distal CCA (0.77 mm ± 0.2 vs 0.68 mm ± 0.15 (p=0.004), and bifurcation (0.85 mm ± 0.25 vs 0.72 mm ± 0.17 (p=0.001). For all arterial segments, a significantly greater number of CIMT measurements were abnormal on the irradiated side (proximal: p=0.004, mid: p=0.05, distal: p=0.005, bifurcation: p=0.03). There was no effect of time from RT, age, smoking status, surgery and chemotherapy on CIMT difference (irradiated-unirradiated) in all segments., Conclusions: CIMT is increased after RT and may be a useful marker of radiation-induced carotid atherosclerosis. There appears to be no additional effect of other atherosclerotic risk factors on CIMT following RT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The authors recently demonstrated that simultaneous assessment of myocardial perfusion (MP) and wall motion (WM) by myocardial contrast echocardiography (MCE) is feasible and accurate when incorporated into a clinical stress echocardiography (SE) service. However, it is unknown whether the incremental prognostic value of MP beyond WM, previously shown in research studies, is reproducible when MCE is performed in the clinical arena., Methods: In this prospective study, MCE was performed by multiple operators during routine clinical SE, whose results were classified as normal WM and MP, abnormal WM and MP, or normal WM but abnormal MP. Patients were followed for the prospectively determined combined primary outcome of all-cause mortality, nonfatal myocardial infarction, and late revascularization. Cox regression analyses were performed to identify predictors of outcome., Results: Of 220 patients undergoing simultaneous MCE during SE, 197 patients (90%) with interpretable WM and MP images were available for follow-up at a mean time period of 17 ± 7 months. There were 35 events (six deaths, six myocardial infarctions, and 23 revascularizations). Among prognostic clinical variables, resting left ventricular function, and WM and MP data, abnormal MP at peak stress was the only independent predictor of primary outcome (hazard ratio, 4.41; 95% confidence interval, 1.37-14.20; P = .02). Sequential Cox regression models showed that abnormal MP also carried incremental prognostic value over clinical variables, resting left ventricular function and abnormal WM., Conclusions: In keeping with previous research studies, this prospective study demonstrates the incremental prognostic benefit of MP assessment beyond WM when MCE is incorporated into a clinical SE service., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the diagnostic impact of stress echocardiography (SE) in patients with suspected low-flow, low-gradient aortic stenosis but normal resting transvalvular flow rate., Background: SE may help to distinguish between true severe aortic stenosis and pseudosevere aortic stenosis in patients with low aortic valve area (AVA) and mean gradient. However, if rest flow rate is normal, then SE may not confer any additional diagnostic value, irrespective of resting left ventricular ejection fraction (LVEF) and indexed stroke volume (SVi)., Methods: Sixty-seven patients with suspected low-flow, low-gradient aortic stenosis who underwent SE were retrospectively studied. Following stratification by rest LVEF, SVi, and flow rate-using cutoffs of 50%, 35 ml/m(2), and 200 ml/s, respectively-we tested for significant changes in AVA during SE., Results: Mean age was 77 ± 9 years and 60% of patients were male. Mean values for rest variables were as follows: AVA: 0.77 ± 0.12 cm(2); mean gradient: 27 ± 7 mm Hg; flow rate: 182 ± 37 ml/s; SVi: 32 ± 8 ml/m(2); and LVEF: 45 ± 15%. During SE, significant increases in AVA were observed regardless of resting LVEF and SVi state. In patients with rest flow rate ≥200 ml/s, AVA did not increase significantly during stress (rest AVA: 0.90 cm(2) vs. stress AVA: 0.97 cm(2); p = 0.11), and positive predictive value for confirming underlying true severe aortic stenosis was 84%. In adjusted analyses, rest flow rate was the only parameter associated with severe AS (odds ratio: 1.05, 95% confidence interval: 1.0 to 1.1; p = 0.002)., Conclusions: Rest AVA measured under normal flow rate conditions is likely to reflect the true severity of AS and unlikely to change significantly with SE. Flow normalization may only be required in patients with AVA <1 cm(2) and mean gradient <40 mm Hg when the rest flow rate is <200 ml/s., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

An automated attenuation correction and normalisation algorithm was developed to improve the quantification of contrast enhancement in ultrasound images of carotid arteries. The algorithm first corrects attenuation artefact and normalises intensity within the contrast agent-filled lumen and then extends the correction and normalisation to regions beyond the lumen. The algorithm was first validated on phantoms consisting of contrast agent-filled vessels embedded in tissue-mimicking materials of known attenuation. It was subsequently applied to in vivo contrast-enhanced ultrasound (CEUS) images of human carotid arteries. Both in vitro and in vivo results indicated significant reduction in the shadowing artefact and improved homogeneity within the carotid lumens after the correction. The error in quantification of microbubble contrast enhancement caused by attenuation on phantoms was reduced from 55% to 5% on average. In conclusion, the proposed method exhibited great potential in reducing attenuation artefact and improving quantification in contrast-enhanced ultrasound of carotid arteries., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: This prospective study investigated whether the incorporation of myocardial contrast echocardiography (MCE) into a clinical stress echocardiography service reproduces the benefits of assessing myocardial perfusion proved previously in research studies., Methods: MCE was performed during physiologic and pharmacologic clinical stress echocardiographic studies, and the value of myocardial perfusion to the reporting echocardiologists was categorized as of benefit (subclassified as incremental benefit over wall motion [WM] or greater confidence with WM) or of no added benefit. The presence and extent of inducible ischemia by WM and myocardial perfusion were documented and correlated with angiographic results in patients who underwent cardiac catheterization., Results: In total, 220 patients underwent simultaneous MCE during stress echocardiography by eight different operators. Overall, MCE was of benefit in 193 patients (88%), providing incremental benefit over WM in 25% and greater confidence with WM evaluation in 62%. MCE provided no added benefit in 27 patients (12%). MCE detected significantly more cases of ischemia than WM in the left anterior descending coronary artery territory (65% vs 53%, P = .02) and detected a greater ischemic burden than WM on a per patient basis (median, 5 [interquartile range, 3-8] vs 4 [interquartile range, 2-7] segments; P < .001) and across all coronary territories. MCE correctly identified a greater proportion of patients with multivessel disease than WM (76% vs 56%, P = .02) and a greater ischemic burden in patients with multivessel disease (median, 7 [interquartile range, 4-9] vs 5 [interquartile range, 1-8] segments; P < .001)., Conclusions: This prospective study is the first to demonstrate that the excellent feasibility and diagnostic utility of MCE, which have been documented in the research arena, are reproducible in the clinical arena., (Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Carotid arteries frequently receive significant incidental doses of radiation during the treatment of malignant diseases, including head and neck cancer, breast cancer and lymphoma. Vascular injury after treatment may result in carotid artery stenosis and increased risk of neurological sequelae, such as stroke and transient ischaemic attack. The long latent interval from treatment to the development of clinical complications makes investigation of this process difficult, particularly in regard to the design of interventional clinical studies. Nevertheless, there is compelling clinical evidence that radiation contributes to carotid atherosclerosis. This overview examines the effect of radiotherapy on the carotid arteries, the underlying pathological processes and their clinical manifestations. The use of serum biomarkers in risk-prediction models and the potential value of new imaging techniques as tools for defining earlier surrogate end points will also be discussed., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this study was to define age-, sex-, and ethnicity-specific reference values for 3-dimensional echocardiographic (3DE) left ventricular (LV) volumes and LV ejection fraction (LVEF) in a large cohort of European white and Indian Asian subjects., Background: Transthoracic 3DE imaging is recommended for the routine evaluation of LV volumes and function. However, there remains a lack of population-based reference values for 3DE LV volumes and LVEF, hindering adoption of this technique into routine clinical practice., Methods: We identified subjects from the LOLIPOP (London Life Sciences Prospective Population) study who were free of clinical cardiovascular disease, hypertension, and type 2 diabetes. All subjects underwent transthoracic 2-dimensional and 3D echocardiography for quantification of LV end-systolic volume index, LV end-diastolic volume index, and LVEF., Results: 3DE image quality was satisfactory in 978 subjects (89%) for the purposes of LV volumetric analysis. Indexed 3DE LV volumes were significantly smaller in female compared with male subjects and in Indian Asians compared with European whites. Upper limit of normal (mean ± 2 SD) reference values for the LV end-systolic volume index and LV end-diastolic volume index for the 4 ethnicity-sex subgroups were, respectively, as follows: European white men, 29 ml/m(2) and 67 ml/m(2); Indian Asian men, 26 ml/m(2) and 59 ml/m(2); European white women, 24 ml/m(2) and 58 ml/m(2); Indian Asian women, 23 ml/m(2) and 55 ml/m(2), respectively. Compared with 3DE studies, 2-dimensional echocardiography underestimated the LV end-systolic volume index and LV end-diastolic volume index by an average of 2.0 ml/m(2) and 4.7 ml/m(2), respectively. LVEF was similar between in all 4 groups and between 2- and 3-dimensional techniques, with a lower cutoff of 52% for the whole cohort., Conclusions: These reference values are based on the largest 3DE study performed to date that should facilitate the standardization of the technique and encourage its adoption for the routine assessment of LV volumes and LVEF in the clinical echocardiography laboratory. This study supports the application of ethnicity-specific reference values for indexed LV volumes., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Indian Asians living in the United Kingdom have a >50% higher risk of cardiovascular disease (CVD) death compared with native European whites. The mechanisms underlying their excess mortality are not clear, and there are no validated tools capable of identifying this increased risk. The burden of subclinical atherosclerosis detected in the carotid arteries is an established prognosticator for major CVD events. We hypothesized that the increased prevalence of CVD among Indian Asians would be reflected by their having a greater burden of subclinical carotid artery atherosclerosis compared with European whites., Methods: We studied 2,288 healthy subjects and 148 patients with known CVD from the London Life Sciences Prospective Population study who underwent carotid ultrasonography for assessment of intima-media thickness (IMT), plaque prevalence, and plaque echogenicity., Results: The prevalence of CVD was significantly higher among Indian Asians compared with European whites (odds ratio 1.72, 95% CI 1.2-2.3). Intima-media thickness was slightly higher in European whites compared with that of Indian Asians (0.66 vs 0.65 mm, P = .06), reflecting their higher Framingham Risk Score. After adjustment for cardiovascular risk factors, there were no significant differences in IMT, plaque prevalence, or plaque echogenicity between the 2 ethnic groups regardless of CVD status., Conclusion: The burden of carotid atherosclerosis does not identify the markedly increased risk of CVD among United Kingdom Indian Asians. Other markers and mechanisms of disease require investigation in this high-risk group., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Subclinical carotid atherosclerosis has been associated with impaired left ventricular (LV) function and the development of heart failure. Whether impaired LV function is related primarily to increased intima-media thickness (IMT) or burden of plaque disease or both remains to be determined., Methods: A total of 2,279 subjects without clinical cardiovascular disease recruited from the London Life Sciences Prospective Population cohort study were studied. Carotid ultrasonography and transthoracic echocardiography were performed on all subjects. Carotid IMT and plaque scores were measured, and their relationships with LV volumes, LV ejection fraction, myocardial LV longitudinal function (Sa and Ea velocities), and LV filling pressure (E/Ea ratio) were assessed before and after adjustment for covariates., Results: Compared with those without carotid artery disease, subjects with either increased IMT and/or presence of plaque disease had identical Sa velocities (both 9.0 cm/sec), lower Ea velocities (8.7 vs 9.9 cm/sec, P < .001) and higher E/Ea ratios (8.4 vs 7.6, P < .001). After multiple linear regression analysis, increasing IMT remained independently related to reduced Ea velocity (P < .001) but not LV ejection fraction, Sa velocity, or E/Ea ratio. In a separate adjusted analysis, subjects with severe burdens of carotid plaque disease (more than five plaques) had reduced LV ejection fractions (β = -2.9; 95% confidence interval [CI], 1.0 to 4.8, P = .003), attenuated Sa velocities (β = -0.79; 95% CI, -1.2 to -0.3, P = .003), attenuated Ea velocities 2 (β = -0.79; 95% CI, -1.3 to -0.2, P = .007), and increased E/Ea ratios (β = 0.84; 95% CI, 0.2 to 1.5, P = .009) compared to individuals without carotid plaques., Conclusion: These findings demonstrate that subclinical carotid plaque disease rather than IMT is more closely related to LV systolic function and LV filling pressure. These data support the application of carotid ultrasonography beyond cardiovascular disease risk prediction, while providing insight into potential mechanisms underlying the development of subclinical LV dysfunction., (Copyright © 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Aims: Remodelling of the left ventricle (LV) is associated with adverse cardiovascular events, but the mechanisms of these effects remain undefined. We investigated the relationship of LV mass and geometry to LV function in a large cohort of hypertensive subjects., Methods and Results: We studied 1074 hypertensive individuals without cardiovascular disease recruited from the London Life Sciences Prospective Population (LOLIPOP) study. All subjects underwent echocardiography for derivation of LV mass index (LVMI), measurement of transmitral filling pattern, and LV ejection fraction (EF). The tissue Doppler parameters of peak myocardial systolic velocity (Sa), diastolic velocity (Ea), and of LV filling pressure (E/Ea) were measured. Left ventricular function was correlated with degree of concentric remodelling, determined by relative wall thickness, and with LV geometric pattern. The presence of LV hypertrophy was independently associated with significantly worse systolic function, diastolic function, and higher LV filling pressure when compared with subjects with normal LV geometry or non-hypertrophic concentric remodelling. After adjustment for covariates including LVMI, peak Sa velocity and EF increased (P < 0.001), whereas peak Ea velocity decreased significantly (P < 0.001) with increasing degrees of concentric remodelling., Conclusion: In hypertensives, hypertrophic remodelling is independently associated with impaired LV function and increased LV filling pressure. Increasing degrees of non-hypertrophic concentric remodelling are associated with attenuated diastolic function, but augmented systolic function, possibly representing an adaptive response to pressure overload physiology.

Objectives: The authors studied healthy UK Indian Asian and European white subjects to assess whether functional, structural and geometrical properties of the left heart are intrinsically related to ethnicity., Background: Quantitative assessment of cardiac function and structure is necessary to diagnose heart failure syndromes and is validated to refine risk prediction. A better understanding of the demographic factors that influence these variables is required., Methods: 458 healthy subjects were recruited from the London Life Sciences Prospective Population (LOLIPOP) study. They underwent 2-D and tissue Doppler echocardiography for quantification of left ventricular (LV) function, LV volumes, left atrial volume index (LAVI), left ventricular mass index (LVMI) and relative wall thickness (RWT)., Results: Indian Asians had attenuated mitral annular systolic velocity (8.9 cm/s vs 9.5 cm/s, p<0.001), lower mitral annular early diastolic velocity (10.3 cm/s vs 11.0 cm/s, p<0.001) and higher E/Ea ratio (7.9 vs 7.0, p<0.001) compared to European white subjects. Although Indian Asians had significantly smaller left heart volumes and LVMI, they had a significantly higher RWT (0.37 vs 0.35, p<0.001). After adjustment for covariates, these ethnicity-related differences remained highly significant (p<0.001)., Conclusion: Compared to European white people, Indian Asians had attenuated longitudinal LV function, higher LV filling pressure and demonstrated a greater degree of concentric remodelling independent of other demographic and clinical parameters.

The significant advances made in ultrasound microbubble technology now permits reliable, reproducible left ventricular opacification, and this review reiterates the evidence that has shown contrast echocardiography to be clinically effective, to reduce downstream costs and to spare patients further, potentially hazardous investigations. Despite the evidence and the advances, there remains ambivalence towards the administration of contrast agents in echocardiography laboratories throughout the world, particularly in the performance of rest studies. Therefore, this review also addresses some of the reasons for the suboptimal uptake of contrast agents and encourages physicians, sonographers, and accreditatory bodies to adopt a different approach towards the difficult-to-image patient., (2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Tissue Doppler imaging (TDI) is used routinely to quantify left ventricular function and filling pressure. However, there remains a lack of percentile-based normative reference values for these clinically important parameters., Methods: Four hundred and fifty-three healthy subjects aged 35-75 years were included for analysis from the London Life Sciences Prospective Population (LOLIPOP) study. Subjects were free of manifest cardiovascular disease, cardiovascular risk factors, and significant coronary artery disease as determined by electron-beam computed tomography. They underwent 2D and Doppler echocardiography for assessment of left heart structure and function. TDI was performed at the septal and lateral mitral annular sites enabling on-line derivation of myocardial systolic velocity (Sa), diastolic velocity (Ea), and the ratio of Ea to transmitral E-wave (E/Ea)., Results: Reference ranges (5th and 95th percentile values) for septal, lateral, and average mitral annular Sa velocity, Ea velocity, and E/Ea ratio were derived for the whole cohort and for each of the four age groups (35-44, 45-54, 55-64, 65-75). Increasing age was associated with a significant attenuation in myocardial velocity when averaged from both the septal and lateral mitral annulus, exerting a greater influence upon average Ea velocity (P < 0.001) compared with average Sa velocity (P = 0.04). Average E/Ea ratio increased significantly with advancing age (P < 0.001)., Conclusion: The reference ranges presented for the TDI parameters of Sa velocity, Ea velocity, and E/Ea ratio will help to standardize the assessment of LV function by tissue Doppler echocardiography.