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OBJECTIVES: This study aimed to assess the value of low transvalvular flow rate (FR) for the prediction of mortality compared with low stroke volume index (SVi) in patients with low-gradient (mean gradient

Objective First-phase ejection fraction (EF1) is a novel measure of early left ventricular systolic dysfunction. We investigated determinants of EF1 and its prognostic value in aortic stenosis. Methods EF1 was measured retrospectively in participants of an echocardiography/cardiovascular magnetic resonance cohort study which recruited patients with aortic stenosis (peak aortic velocity of ≥2 m/s) between 2012 and 2014. Linear regression models were constructed to examine variables associated with EF1. Cox proportional hazards were used to determine the prognostic power of EF1 for aortic valve replacement (AVR, performed as part of clinical care in accordance with international guidelines) or death. Results Total follow-up of the 149 participants (69.8% male, 70 (65–76) years, mean gradient 33 (21–42) mm Hg) was 238 029 person-days. Sixty-seven participants (45%) had a low baseline EF1 (

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.Low transaortic flow may complicate grading of AS. However, the association of lower transaortic FR with adverse outcomes has not been reported.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).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/mIn 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).

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

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

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.

ObjectivesThis 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.BackgroundSE 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).MethodsSixty-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/m2, and 200 ml/s, respectively—we tested for significant changes in AVA during SE.ResultsMean age was 77 ± 9 years and 60% of patients were male. Mean values for rest variables were as follows: AVA: 0.77 ± 0.12 cm2; mean gradient: 27 ± 7 mm Hg; flow rate: 182 ± 37 ml/s; SVi: 32 ± 8 ml/m2; 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 cm2 vs. stress AVA: 0.97 cm2; 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).ConclusionsRest 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

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.

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.

Carotid arteries frequently receive significant doses of radiation as collateral structures in the treatment of malignant diseases. Vascular injury following treatment may result in carotid artery stenosis (CAS) and increased risk of stroke and transient ischaemic attack (TIA). This systematic review examines the effect of radiotherapy (RT) on the carotid arteries, looking at the incidence of stroke in patients receiving neck radiotherapy. In addition, we consider possible surrogate endpoints such as CAS and carotid intima-medial thickness (CIMT) and summarise the evidence for radiation-induced carotid atherosclerosis.From 853 references, 34 articles met the criteria for inclusion in this systematic review. These papers described 9 studies investigating the incidence of stroke/TIA in irradiated patients, 11 looking at CAS, and 14 examining CIMT.The majority of studies utilised suboptimally-matched controls for each endpoint. The relative risk of stroke in irradiated patients ranged from 1.12 in patients with breast cancer to 5.6 in patients treated for head and neck cancer. The prevalence of CAS was increased by 16-55%, with the more modest increase seen in a study using matched controls. CIMT was increased in irradiated carotid arteries by 18-40%. Only two matched-control studies demonstrated a significant increase in CIMT of 36% and 22% (p=0.003 and0.001, respectively). Early prospective data demonstrated a significant increase in CIMT in irradiated arteries at 1 and 2 years after RT (p0.001 and0.01, respectively).The incidence of stroke was significantly increased in patients receiving RT to the neck. There was a consistent difference in CAS and CIMT between irradiated and unirradiated carotid arteries. Future studies should optimise control groups.

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/m2 and 67 ml/m2; Indian Asian men, 26 ml/m2 and 59 ml/m2; European white women, 24 ml/m2 and 58 ml/m2; Indian Asian women, 23 ml/m2 and 55 ml/m2, 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/m2 and 4.7 ml/m2, 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.

The severity of low-flow low-gradient (LFLG) aortic stenosis (AS) during low-dose dobutamine stress echocardiography (LDDSE) is deemed assessable only when stroke volume–determined flow reserve (SVFR) (stroke volume [SV] increase ≥20%) is present. However, due to typically frequently

Myocardial Contrast Echocardiography (MCE) with micro-bubble contrast agent enables myocardial perfusion quantification which is invaluable for the early detection of coronary artery diseases. In this paper, we proposed a new segmentation method called Shape Model guided Random Forests (SMRF) for the analysis of MCE data. The proposed method utilizes a statistical shape model of the myocardium to guide the Random Forest (RF) segmentation in two ways. First, we introduce a novel Shape Model (SM) feature which captures the global structure and shape of the myocardium to produce a more accurate RF probability map. Second, the shape model is fitted to the RF probability map to further refine and constrain the final segmentation to plausible myocardial shapes. Evaluated on clinical MCE images from 15 patients, our method obtained promising results (Dice=0.81, Jaccard=0.70, MAD=1.68 mm, HD=6.53 mm) and showed a notable improvement in segmentation accuracy over the classic RF and its variants.

Individuals of Indian Asian ethnicity living in the U.K. have at least a 50% excess of cardiovascular disease (CVD) mortality compared with European whites, yet there are no validated tools capable of identifying this excess risk. Left ventricular hypertrophy (LVH) is a powerful prognosticator for future CVD events but its prevalence in Indian Asians is unknown. We examined the prevalence of LVH and the degree of concentric remodeling amongst healthy U.K. Indian Asians compared with European whites recruited to the LOLIPOP (London Life Sciences Prospective Population) study. Transthoracic echocardiography was performed in 2127 subjects aged 35-75 years without history of clinical CVD events. The prevalence of LVH was defined and relative wall thickness was calculated to provide a measure of concentric remodeling. The prevalence of LVH was significantly higher amongst Indian Asian men as compared with European white men, with an unadjusted odds ratio (OR) of 1.8 (95% CI: 1.4-2.6). Following adjustment for clinical and hemodynamic variables, the magnitude of this effect increased (OR 2.8, 95% CI: 1.9-4.2). The degree of concentric remodeling was higher amongst Indian Asians as compared with European whites (adjusted relative wall thickness for men: 0.41 vs. 0.39, P0.001; women: 0.40 vs. 0.38, P0.01). An almost threefold higher prevalence of LVH amongst Indian Asian men and a greater degree of concentric remodeling amongst Indian Asian men and women was evident. Investigation of the mechanisms underlying the pathogenesis of LV remodeling and blood pressure etiology may help redress the excess CVD mortality observed in Indian Asians.

Background During low-dose dobutamine stress echocardiography (LDDSE) in low-flow low-gradient aortic stenosis (LFLGAS), both the aortic stenosis (AS) severity and the presence of contractile reserve (CR) are conventionally assessed based on stroke volume flow reserve (SVFR), which is defined as stroke volume [SV] increase 20%. However frequent exaggerated chronotropic response to dobutamine with shortening left ventricular time result in SV drop. On the contrary, transvalvular flow rate (FR) (SV/ejection time) and left ventricular ejection fraction (LVEF) may increase. We aimed to assess the value of FR 200 ml/s (normal FR) and LVEF change in the identification of true severe AS (TSAS) and the assessment of CR respectively. Methods Accordingly 74 consecutive patients (mean age 78 years) with LFLGAS referred for LDDSE for determination of AS severity and CR underwent retrospective assessment of SV, FR, LVEF and standard echocardiographic parameters of AS severity (Table 1). The outcome assessed was all-cause mortality censored for aortic valve intervention. Results SVFR was present in 30 (40.5%) of the 74 patients whereas FR 200 ml/s was achieved in 60 (81.1%) (p Conclusions During LDDSE in LFLGAS normalised FR, not SVFR, is a better determinant of TSAS, whereas assessment of LVEF change instead of SVFR determines CR.

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.

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.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.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.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.

The aim of the study was to assess whether myocardial contrast echocardiography (MCE) can predict mortality in patients with heart failure. Myocardial viability, ischaemia, and coronary flow reserve (CFR) are predictors of mor- tality in patients with heart failure. MCE can assess myocardial viability, ischaemia, and CFR at the bedside. However, its prognostic value is unknown in patients with heart failure. Methods and results Eighty-seven patients (age: 68+10 years, 62% male) with heart failure (left ventricular ejection fraction (LVEF): 35%+13) underwent low-power intermittent MCE at rest and 2 min after dipyridamole infusion. Resting and stress perfusion score index were derived qualitatively. CFR (MBF at stress/MBF at rest) was calculated by a quan- titative method. All patients underwent coronary arteriography. Patients were followed up for mortality. Of the 87 patients, 43 (49%) patients had coronary artery disease. There were 28 (32%) deaths during a mean follow-up of 4.1+1.7 years. Type 2 diabetes (P ¼ 0.02, hazard ratios (HR) 2.43, confidence interval (CI) 1.13-5.22) and CFR (P ¼ 0.001, HR 0.15, CI 0.05-0.45) were independent predictors of mortality. A CFR ≤ 1.5 had a significantly (P , 0.0001) higher mortality of 49 vs. 10% in patients with CFR . 1.5 over the 4 year follow-up period. Conclusion CFR determined by MCE is a powerful predictor of mortality in patients with heart failure.

The objectives of low-dose dobutamine stress echocardiography (LDDSE) in low-flow low-gradient aortic stenosis (LFLG AS) are both to normalise transvalvular flow, at which juncture the aortic valve area informs the true AS severity, and to assess flow reserve. Conventionally, these assessments are

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.

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.

The aim of this study was to determine the effect of radiotherapy (RT) on intraplaque neovascularization (IPN) in human carotid arteries.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.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).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.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.

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

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.

Background: During low-dose dobutamine stress echocardiography in low-flow low-gradient aortic stenosis (LFLGAS), both the aortic stenosis severity and the presence of contractile reserve are conventionally assessed based on stroke volume flow reserve (SVFR) (stroke volume increase ≥20%). However

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.

Appropriateness criteria for stress echocardiography (SE) have been published to reduce the rate of inappropriate testing. We sought to investigate the clinical impact and prognostic value of these criteria.250 consecutive patients undergoing SE for evaluation of coronary artery disease were classified into appropriate, uncertain and inappropriate categories according to appropriateness criteria. A positive SE was defined as the development of new wall motion abnormalities or a biphasic response. The primary end point was the composite of myocardial infarction and death.Of the 250 SE, 120 (48%) were dobutamine studies and 130 (52%) were exercise studies. 156 (62.4%), 71 (28.4%) and 23 (9.2%) were classified as appropriate, inappropriate and uncertain, respectively. A significantly greater proportion of studies classified as appropriate 71 (45.5%) demonstrated inducible ischaemia compared with inappropriate studies 9 (12.7%) or uncertain studies 4 (17.4%), p0.0001. During a median follow-up of 12.4 months, events occurred in 18 (11.5%), 2 (2.8%) and 0 patients classified as appropriate, inappropriate and uncertain, respectively. Event-free survival was significantly reduced in patients with a SE demonstrating ischaemia compared with patients without inducible ischaemia, p0.0001. Kaplan-Meier curves demonstrated reduced event-free survival in patients with whose studies were classified as appropriate compared to inappropriate (p=0.01) or uncertain (p=0.05).Appropriateness criteria differentiate between patients at high risk of ischaemia, subsequent revascularisation/cardiac events (appropriate group) and those at low risk of events (inappropriate group). A large proportion of SE is currently performed in inappropriate patients. Implementation of the criteria in clinical practice would reduce unnecessary testing.

An asymptomatic 72-year-old man with cardiomegaly was referred to our centre for assessment. His medical history comprised metastatic colonic cancer and granulomatosis with polyangiitis. Transthoracic echocardiography was performed. In the apical four-chamber view, a large cavity was identified adjacent to the apex, measuring 45 × 54 mm (Fig. 1A and Supplementary Video 1). All apical segments of the left ventricle were thin and akinetic. On colour Doppler, bidirectional blood flow due to swirling of blood was observed within the cavity (Fig. 1B and Supplementary Video 2). Contrast-enhanced echocardiography established the site of rupture within the thinned apical wall of the left ventricle, measuring 15 mm in width, communicating freely with a large, thrombus-free pseudoaneurysm (Fig. 1C and Supplementary Video 3). Cardiovascular magnetic resonance imaging confirmed the finding of an apical pseudoaneurysm (Fig. 1D and Supplementary Video 4). Late gadolinium enhancement was limited to the apical segments in a transmural distribution. The remaining segments of the left ventricle were functioning and viable with no evidence of inducible ischaemia. Coronary angiography demonstrated unobstructed arteries. Figure 1: (A) Transthoracic echocardiogram; four-chamber view. (B) Colour Doppler showing bidirectional flow of blood within the left ventricular pseudoaneurysm. (C) Contrast-enhanced transthoracic echocardiogram, zoomed on the left ventricular pseudoaneurysm. ... In this case, the likely primary event was an unrecognized myocardial infarction, followed by ventricular wall rupture contained within pericardial tissue. Possible mechanisms for the myocardial infarction include acute coronary artery occlusion with spontaneous recanalization, coronary thromboembolism and coronary vasculitis. This patient's case was discussed in a multidisciplinary team meeting. The consensus view was that the risk of rupture of the pseudoaneurysm was small. Furthermore, the patient's survival was estimated to be 1 year due to his metastatic colonic cancer. Consequently, medical treatment was advised. The natural history of left ventricular pseudoaneurysms is not known. If left untreated, left ventricular pseudoaneurysms predispose to ventricular rupture, thromboembolism, compression of local structures and arrhythmia. Most pseudoaneurysms require surgical intervention [1] or percutaneous closure [2]. When a left ventricular pseudoaneurysm is chronic, there are limited outcome data to guide the need for surveillance and timing of intervention. This case illustrates the value of contrast-enhanced echocardiography as a low cost adjunct to complex imaging modalities, to rapidly distinguish left ventricular pseudoaneurysms from other cardiac pathology. No ethical approval is required. The patient provided written consent. R.S. is nominated as the guarantor of this work.

A 64-year-old woman presented to a district general hospital with left-sided chest pain that radiated through to the back. Her medical history included a previous myocardial infarction. After assessment in the emergency department, acute aortic dissection was suspected, and a computed tomography (CT) aortogram was performed (Figure, A). This aortogram did not demonstrate evidence of acute aortic pathology. However, a soft-tissue mass was visualized in the left upper mediastinum adjacent to the distal aortic arch, suggestive of either an inflammatory process or a neoplastic lesion. She was referred to our center for further investigation. A CT-guided biopsy of the mass was scheduled ≈4 weeks after initial presentation. In view of her history of ischemic heart disease, she …

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.

Dear EditorIt is known that judging the severity of aortic stenosis (AS) in pa-tients with co-existent left ventricular (LV) systolic dysfunction can bechallenging. These patients are particularly difficult for the managingclinicianastheir operativeriskis high butoutcomewith medical thera-py is poor. Quantitative Doppler echocardiography permits calculationof the aortic valve area (AVA), which may be b1.0 cm

We examined the prognostic value of stress echocardiography appropriateness criteria for evaluation of valvular heart disease in 100 consecutive patients. Of the studies, 49%, 36%, and 15% were classified as appropriate, uncertain, and inappropriate, respectively. Over a median of 12.6 months, 24 events (12 deaths and 12 heart failure admissions) occurred. The 12-month event-free survival was significantly reduced in patients with appropriate or uncertain studies compared with patients with inappropriate studies (p = 0.04 and p = 0.005, respectively). There was no survival difference between patients with an appropriate or uncertain indication (p = 0.1). The only independent predictors of events were a positive stress echocardiogram (hazard ratio: 15.5, p < 0.0001) and left ventricular ejection fraction (hazard ratio: 0.95, p = 0.02). The appropriateness criteria for evaluation of valvular heart disease provide the ability to differentiate between patients at high- (appropriate group) and low- (inappropriate group) risk of cardiac events. Reclassification of the uncertain group may improve the differential value of these criteria.

Temporo-mandibular joint (TMJ) dislocation is an unusual complication of transoesophageal echocardiography (TEE). We report a rare case of bilateral TMJ dislocation in an 84-year-old man prior to DC cardioversion (DCCV) for atrial flutter. Shortly after TEE and DCCV, the patient complained of bilateral facial pain. An orthopantomogram revealed bilateral TMJ dislocation. A closed reduction was performed by Maxillo-facial surgeons under intravenous anaesthesia. Although very uncommon, the physician should be aware of the complication and its management.

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.

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.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.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).Indian Asians had attenuated mitral annular systolic velocity (8.9 cm/s vs 9.5 cm/s, p0.001), lower mitral annular early diastolic velocity (10.3 cm/s vs 11.0 cm/s, p0.001) and higher E/Ea ratio (7.9 vs 7.0, p0.001) 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, p0.001). After adjustment for covariates, these ethnicity-related differences remained highly significant (p0.001).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.

Limited studies are available demonstrating the safety of contrast agents in patients undergoing stress echocardiography and none in patients with suspected acute coronary syndrome (ACS). Therefore, we sought to assess the safety profile of contrast agents in patients with stable chest pain and in those with suspected ACS (nondiagnostic electrocardiogram and negative initial 12-hour cardiac troponin test results). During a 4-year period, 3,704 patients underwent stress echocardiography (exercise or dobutamine), of whom, 929 (25%) had suspected ACS. Contrast agents (SonoVue 46%, Luminity 54%) were used in 1,150 patients (31%). No patients died with or without contrast administration. No nonfatal acute myocardial infarction occurred in patients administered contrast agents compared with 3 cases of acute myocardial infarction in the noncontrast group (p = 0.24). Two cases of sustained ventricular tachycardia developed, one in each group (p = 0.98). Compared with those who did not receive contrast, patients in both the stable chest pain and the suspected ACS groups had a greater burden of cardiovascular risk factors. The left ventricular function at rest was significantly worse in the patients who received contrast than in those who did not in the suspected ACS group. Also, a greater ischemic burden was present in those receiving contrast than in those not receiving it in both the stable chest pain and the suspected ACS groups. In conclusion, despite the presence of greater risk features compared with patients undergoing unenhanced stress echocardiography, the administration of ultrasound contrast agents (SonoVue and Luminity) in those with stable chest pain and those with suspected ACS was not associated with excess adverse events.

Objectives The purpose of this study was to compare the diagnostic impact of stress echocardiography (SE) in patients with suspected low-flow low-gradient aortic stenosis (LFLGAS) but normal resting transvalvular flow rate. Background SE may help to distinguish between true LFLGAS, and pseudo severe stenosis in patients with low aortic valve area (AVA) and mean gradient (MG). 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 Thirty-nine patients with suspected LFLGAS who underwent SE in a single institution were retrospectively studied. Following stratification by rest LVEF, SVi and flow rate – using cut-offs of 40%, 35 ml/m 2 and 200 ml/sec respectively – we tested for significant changes in AVA during SE. Results Mean age was 77 ± 8 years and 72% were male. Mean values for rest variables were: AVA 0.79 ± 0.13 cm 2 ; MG 26 ± 6 mmHg; flow rate 186 ± 37 ml/s; SVi 33 ± 8 ml/m 2 and LVEF 44 ± 15%. During stress, significant increases in AVA were observed regardless of resting LVEF and SVi status, and only in patients with low rest flow rate. In patients with rest flow rate >200 ml/s, AVA did not increase significantly during stress (rest AVA 0.90 cm 2 vs stress 0.97 cm 2 , p = 0.11). In adjusted analyses, rest flow rate was the only parameter associated with severe AS (OR=0.94, p = 0.01). 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 rate normalisation during stress may only be required in patients with AVA 2 and transvalvular mean gradient

Background The prognostic value of myocardial perfusion (MP), assessed during stress echocardiography (SE) by myocardial contrast echocardiography (MCE), has been shown in research studies but is untested in a ‘real-world’ clinical SE service. Methods Patients clinically referred for SE undergoing pharmacological stress, and those doing exercise stress in whom we suspected target heart rate may not be attained, underwent MCE using Sonovue contrast. We documented prospectively patient demographics and SE results by wall motion (WM)and MP. Patients were followed-up for the outcomes of death, myocardial infarction (MI) and late revascularisation. Results Of 220 patients that underwent MCE during SE, 204(93%) were followed-up. Mean age was 66yrs, 74% were male and 66% had known CAD. Over a mean follow-up period of 16 ± 7 months, there were 35 (17%) events (6 deaths,6 non-fatal MIs and 23 revascularizations). Univariate Cox regression revealed that a history of CAD, inducible ischemia by WM and by MP predicted outcome. On multivariate analysis, inducible ischemia by MP was the strongest predictor of outcome (HR 3.92, p = 0.016) and ischemia by WM did not predict outcome. Kaplan-Meier survival curves showed that patients with abnormal MP (in isolation or combined with WM) had significantly worse outcome than patients with normal MP and WM (Log-rank score 12.6, p = 0.006). Conclusion Simultaneous MP assessment by MCE, incorporated into a real-world clinical SE service, has incremental prognostic value beyond WM analysis alone.

We examined the prognostic value of stress echocardiography appropriateness criteria for evaluation of valvular heart disease in 100 consecutive patients. Of the studies, 49%, 36%, and 15% were classified as appropriate, uncertain, and inappropriate, respectively. Over a median of 12.6 months, 24 events (12 deaths and 12 heart failure admissions) occurred. The 12-month event-free survival was significantly reduced in patients with appropriate or uncertain studies compared with patients with inappropriate studies (p ¼ 0.04 and p ¼ 0.005, respectively). There was no survival difference between patients with an appropriate or uncertain indication (p ¼ 0.1). The only independent predictors of events were a positive stress echocardiogram (hazard ratio: 15.5, p < 0.0001) and left ventricular ejection fraction (hazard ratio: 0.95, p ¼ 0.02). The appropriateness criteria for evaluation of valvular heart disease provide the ability to differentiate between patients at high- (appropriate group) and low(inappropriate group) risk of cardiac events. Reclassification of the uncertain group may improve the differential value of these criteria.

A 43-year-old male with a recent diagnosis of metastatic melanoma presented with syncope and shortness of breath. Transthoracic echocardiography revealed a large circumferential pericardial effusion which was drained percutaneously via an apical approach. Following percutaneous drainage, echocardiography revealed a severely hypertrophied akinetic and hyperechogenic interventricular septum, thickened right ventricular apex, and hypertrophied ventricular right and left free walls, …

Introduction Increased carotid intima-media thickness (IMT) and the presence of carotid plaques are both considered surrogate markers of atherosclerosis. Although inter-related, these two phenotypes represent heterogenous pathophysiological processes. Increased IMT is largely correlated to normal ageing and blood pressure, whereas plaques are synonymous with established atherosclerosis. We sought to determine the distinct relationships of carotid intima-media thickness and carotid plaque disease with quantitative parameters of left ventricular (LV) function. Methods We studied 2279 healthy subjects recruited from the LOLIPOP (London Life Sciences Prospective Population) study free of clinical cardiovascular disease. Bilateral carotid ultrasonography was performed on all subjects to determine presence of carotid plaque, with the total number of plaques identified providing a plaque score. Subjects with a plaque score of 0, 1–2, 3–5 and > 5 were classified as having no, mild, moderate and severe plaque burden respectively. Tissue Doppler imaging was performed on all subjects for derivation of parameters of LV longitudinal function and filling pressure (myocardial Sa velocity, myocardial Ea velocity and the E/Ea ratio). Results Subjects with higher plaque score were older, more likely to be male, have a greater prevalence of hypertension, diabetes and history of cigarette smoking (all p Conclusions This study confirms that distinct relationships exist between different forms of carotid artery disease and LV function. Carotid plaque disease severity, but not increased IMT, is associated with reduced systolic function and increased LV filling pressure in asymptomatic individuals.