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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

Hypertension remains a major contributor to the global burden of disease. The measurement of blood pressure continues to have pitfalls related to both physiological aspects and acute variation. As the left ventricle (LV) remains one of the main target organs of hypertension, and echocardiographic measures of structure and function carry prognostic information in this setting, the development of a consensus position on the use of echocardiography in this setting is important. Recent developments in the assessment of LV hypertrophy and LV systolic and diastolic function have prompted the preparation of this document. The focus of this work is on the cardiovascular responses to hypertension rather than the diagnosis of secondary hypertension. Sections address the pathophysiology of the cardiac and vascular responses to hypertension, measurement of LV mass, geometry, and function, as well as effects of treatment.

Aims Survival in pulmonary arterial hypertension (PAH) and Eisenmenger syndrome (ES) relates to right ventricular (RV) function. Little is known about differences of ventricular function between ES patients and those suffering from other PAH aetiologies. In this study, we compared global ventricular function assessed by speckle-tracking in adult patients with ES, other PAH aetiologies, or healthy controls; and assessed the relationship between ventricular function and survival. Methods and results We performed a prospective cohort study recruiting 83 adult PAH patients (43 ES and 40 other PAH aetiologies patients) and 37 controls between March 2011 and June 2015. Patients with complex congenital heart disease were excluded. Fifty-three patients (63.9%) were in NYHA functional class ≥III at baseline and 60 (72.3%) were on advanced therapies. Mean RV peak longitudinal strain was −16.3 ± 7% in ES, lower compared with healthy controls ( P

While the impact of carotid plaque on cardiovascular events is well investigated in asymptomatic epidemiologic studies, the long-term clinical impact of carotid plaque and its burden (CPB) in patients with new-onset suspected stable angina with no history of coronary artery disease beyond stress echocardiography (SE) is not known. We sought to investigate this with a prospective study, where patients were followed up for adverse events.Consecutive patients referred for SE underwent simultaneous carotid ultrasonography to assess CPB, defined as the total number of carotid plaques per patient. Stress echocardiography was reported off-line using a 17-segments model and four-point wall thickening scoring. Peak wall thickening scoring index was the sum of scores of each segment divided by 17.Of the 592 patients, 573 (age 59 ± 11, 45% male) had follow-up data. During a mean of 7.2 years, 85 patients had a first major adverse event (all-cause mortality and acute myocardial infarction: 68 had hard events and 17 had unplanned revascularization). On multivariate Cox regression analysis, pretest probability of coronary artery disease (P = .048), peak wall thickening scoring index (P .0001), and CPB (P .0001) predicted major adverse events; however, only CPB retained significance for both hard events and hard cardiac events (P = .001 and .0001, respectively). Major adverse events and hard events were the least in patients with normal SE and absent carotid plaque (annualized event rate: 1.1% and 1.02%, respectively), with a significant increase in normal SE and carotid plaque disease (2.4% and 2.05%, P = .004 and P = .01, respectively). The presence of plaque did not have an impact on these outcomes in an abnormal SE cohort.In patients with suspected stable angina with no history of cardiovascular disease, carotid atherosclerosis and myocardial ischemia detected by ultrasound provided synergistic information for the long-term prediction of events, but atherosclerosis predicted hard events beyond myocardial ischemia, particularly in patients with a normal SE.

Purpose of review The current guidelines recommend the use of myocardial contrast echocardiography (MCE) to assess myocardial viability. There are two clinical scenarios where detection of myocardial viability has clinical significance: in ischemic cardiomyopathy and following acute myocardial infarction with significant left ventricular dysfunction. Myocardial contrast echocardiography (MCE), which utilizes microbubbles can assess the integrity of the microvasculature, which sustains myocardial viability in real time and can hence rapidly provide information on myocardial viability at the bedside without ionizing radiation. Recent findings We discuss the value of MCE to predict myocardial viability through the detection of the integrity of myocardial microvasculature, the newer evidences behind the MCE-derived coronary flow reserve and use of MCE postmyocardial infarction to detect no-reflow. Newer studies have also demonstrated the comparable sensitivities and specificities of MCE to single photon-emission computed tomography (SPECT), cardiac myocardial resonance imaging and PET for the detection of myocardial viability. Summary Ample evidence now exist that supports the routine use of MCE for the detection of viability as laid down in recent guidelines.

Introduction Takotsubo syndrome (TTS) is an acute heart failure syndrome usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, approximately 10% of patients have persistent symptoms and seek further medical advice. Purpose To determine the cardiovascular haemodynamic and LV contractile response to exercise in these TTS survivors with ongoing symptoms. Methods This was a case-control study of 20 symptomatic patients with previous TTS referred for treadmill exercise echocardiography (EE), and 20 age-, sex- and ethnicity-matched control subjects with normal treadmill EE. Among the TTS group, EE was performed at a median of 8 months (mean 17±21 months) following the index event. Demographic characteristics, resting and EE data were collected. LV ejection fraction (EF) was measured at rest and peak stress. Global longitudinal and circumferential strain (GLS, GCS) were measured at rest. Results All 20 TTS patients were Caucasian postmenopausal females (mean age 63.5 ± 6.6 years). There were no significant differences in body mass index (BMI), resting heart rate (HR) and the prevalence of cardiovascular risk factors compared to controls. Resting systolic and diastolic blood pressure (SBP, DBP) were higher in TTS patients (144±17 mmHg versus 128±18 mmHg, and 81±10 mmHg versus 74±9 mmHg, respectively). A comparative analysis of the resting and stress echo data is given in table 1. The stress echo data showed similar exercise time and peak HR, but higher peak SBP in TTS patients. TTS patients had blunted contractile response to exercise with lower peak LVEF, ΔLVEF (exercise minus resting EF) and peak wall motion score index (WMSI) compared to controls. Among the 20 TTS patients, 12 had exercise-induced wall motion abnormalities: 6 involved the apical segments and 6 developed global dysfunction. In these 12 patients, the mean ΔLVEF was reduced (4%). In the other 8 patients, the ΔLVEF was 16% and pooled the TTS cohort had blunted contractile response with exercise compared to controls (ΔLVEF 8% vs. 19% in the control group, p=0.001). Conclusion Our study shows that symptomatic patients with previous TTS have a blunted contractile response to exercise manifest as reversible apical or global LV dysfunction. These findings might indicate the need for treatment. Further systematic investigation of the therapeutic and prognostic implications of this reversible exercise-induced myocardial dysfunction is needed. Conflict of Interest no

Introduction To assess the survival benefit of aortic valve replacement (AVR) in patients with normal flow low gradient severe aortic stenosis (AS). Methods A retrospective study of prospectively collected data of 276 patients (mean age 75±15 years, 51% male) with normal transaortic flow (flow rate [FR] ≥200 ml/s or stroke volume index [SVi] ≥35 ml/m2) and severe AS (aortic valve area [AVA] Results Of the 276 patients, 55% (n=151) were medically treated while 45% (n=125) underwent an AVR. Over a mean follow-up of 3.2±1.8 years (range 0–6.9 years) a total of 96 (34.8%) deaths occurred: 17 (13.6%) in AVR group versus 79 (52.3%) in those medically treated, when transaortic flow was defined by FR (p Conclusion In patients with normal flow low gradient severe AS, AVR was associated with a significantly improved survival compared to those who received standard medical treatment. Conflict of Interest No

Background The long-term clinical impact of carotid plaque and carotid plaque burden (CPB) in patients with new onset suspected stable angina beyond stress echocardiography (SE) with no history of coronary artery disease (CAD) is not known. Methods Consecutive patients referred for SE underwent simultaneous carotid ultrasonography to assess CPB. Patients were prospectively followed up for major adverse events (MAE). Results Of the 592 patients, 573 (age 59±11, 45% male) could be followed up. During a mean follow up of 7±1.2 years, 85 patients had first MAE (all-cause mortality and acute myocardial infarction: 67 (hard events) and 18 unplanned revascularisation). On multivariate Cox regression analysis, pre-test probability (PTP) of CAD, peak wall thickness scoring index (pWTSI) and CPB predicted MAE (p Conclusion In patients with suspected stable angina, carotid atherosclerosis and myocardial ischemia in combination provide synergistic MAE information long term but atherosclerosis predicted hard events beyond myocardial ischemia particularly in patients with normal SE. Conflict of Interest None

Multivalvular heart disease (MVD) is a highly prevalent condition causing significant morbidity and mortality. The complex haemodynamic interactions between coexisting valve lesions makes the diagnosis and treatment challenging. Current guidelines may not be adequate for managing the varying clinical scenarios of MVD and, therefore, the expertise of a multidisciplinary Heart Valve Team is of paramount importance. The indications for intervention should be based on a global assessment of the consequences of the multiple valve lesions after a careful estimation of the added surgical risk of combined procedures, the long-term risk of morbidity and mortality associated with multiple valve prostheses and the risk of reoperation if less-than-severe valve lesions are left untreated at the time of first evaluation. Echocardiography plays an important role in assessing patients and, as a general rule, an accurate echo diagnosis needs to combine different measurements. The emerging transcatheter valve therapies should be considered an option for high risk patients. More data on the natural history of MVD and the impact of intervention on outcome are required to better define the optimal management strategy.

To evaluate whether planarSubjects from ADMIRE-HF were followed for approximately 5 years after imaging (964 subjects, median follow-up 62.7 months). Subjects were stratified according to the heart/mediastinum (H/M) ratio ( 1.60 vs ≥ 1.60) on planarDuring a median follow-up of 62.7 months, patients with H/M ≥ 1.60 were at significantly lower risk of death and arrhythmic events independently of LVEF values.

Degenerative or fibrocalcific aortic stenosis (AS) is now the most common native valvular heart disease assessed and managed by cardiologists in developed countries. Transthoracic echocardiography remains the quintessential imaging modality for the non-invasive characterisation of AS due to its widespread availability, superior assessment of flow haemodynamics, and a wealth of prognostic data accumulated over decades of clinical utility and research applications. With expanding technologies and increasing availability of treatment options such as transcatheter aortic valve replacements, in addition to conventional surgical approaches, accurate and precise assessment of AS severity is critical to guide decisions for and timing of interventions. Despite clear guideline echocardiographic parameters demarcating severe AS, discrepancies between transvalvular velocities, gradients, and calculated valve areas are commonly encountered in clinical practice. This often results in diagnostically challenging cases with significant implications. Greater emphasis must be placed on the quality of performance of basic two dimensional (2D) and Doppler measurements (attention to detail ensuring accuracy and precision), incorporating ancillary haemodynamic surrogates, understanding study- or patient-specific confounders, and recognising the role and limitations of stress echocardiography in the subgroups of low-flow low-gradient AS. A multiparametric approach, along with the incorporation of multimodality imaging (cardiac computed tomography or magnetic resonance imaging) in certain scenarios, is now mandatory to avoid incorrect misclassification of severe AS. This is essential to ensure appropriate selection of patients who would most benefit from interventions on the aortic valve to relieve the afterload mismatch resulting from truly severe valvular stenosis.

Aims To assess the survival benefit of aortic valve replacement (AVR) in patients with normal flow low gradient severe aortic stenosis (AS). Methods and results A retrospective study of prospectively collected data of 276 patients (mean age 75 ± 15 years, 51% male) with normal transaortic flow [flow rate (FR) ≥200 mL/s or stroke volume index (SVi) ≥35 mL/m2] and severe AS (aortic valve area Conclusion In patients with normal flow low gradient severe AS, AVR was associated with a significantly improved survival compared with those who received standard medical treatment.

Learning objectives Stress echocardiography is an established technique for the detection of coronary artery disease, but the echocardiographic assessment of valve disease has conventionally been performed under static conditions. However, valve disease also tends to present with exertional symptoms, influenced by changes in haemodynamic conditions provoked by normal physical activity. The changes in heart rate, contractility, loading conditions and left ventricular (LV) compliance during exercise may influence the haemodynamic significance of a given valve lesion. Consequently, in recent years the role of stress echocardiography in valve disease has been studied widely.1–6 The evaluation of valve disease under haemodynamic stress permits the detection of changes in transvalvular gradients, severity of regurgitation, LV contractility, pulmonary artery pressure and concomitant myocardial ischaemia. As valve disease tends to progress slowly, symptoms may develop insidiously, and many patients may either be unaware of the subtle changes in effort tolerance or regard any changes to be non-specific. Stress echocardiography with physiological exercise is uniquely placed, beyond other imaging modalities, in enabling an objective assessment of functional capacity and correlation of symptoms with the severity of valve disease and LV contractile response. In general terms, a severe valve lesion causing symptoms or LV dysfunction usually warrants intervention.7 8 However, management may be unclear in those with severe valve disease without symptoms, non-severe valve disease with symptoms or valve disease with low flow. Under these circumstances stress echocardiography may provide additional information, helpful in the decision-making …

The major requirement for optimal echocardiographic image interpretation, reproducibility, and diagnostic accuracy is image quality. Despite the use of harmonics, a significant proportion of patients have challenging images, which has an impact on diagnosis and management. The ultrasound contrast agents (UCAs), which are administered intravenously, have been a significant development in image quality optimization and have proved to be an important aid in the assessment of structural abnormalities, detection of regional wall motion abnormalities, and calculation of left ventricular ejection fraction. The use of UCAs is also of critical importance for the detection of ischaemia and the assessment of significant coronary artery disease through detection of inducible regional wall motion abnormalities during stress echocardiography. UCAs can also assess myocardial perfusion, which improves assessment of myocardial ischaemia during stress echocardiography. Similarly the simultaneous assessment of wall motion and perfusion improves assessment of viable myocardium in patients with left ventricular dysfunction. As the use of UCAs results in increased feasibility, reproducibility, and diagnostic and prognostic accuracy of echocardiography including cost-efficiency, both European and American guidelines endorse its use in clinical cardiology.

Stress echocardiography is a well-established imaging modality that combines echocardiography with exercise or pharmacologic or electrical stress to diagnose coronary artery disease, assess severity of valve disease, and investigate potential viability of the cardiac muscle. In the era of tissue harmonic imaging and ultrasound contrast agents, stress echocardiography has established itself as an accurate technique with diagnostic images obtained in almost all patients.

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited pathology that can increase the risk of sudden death. Current task force criteria for echocardiographic diagnosis do not include new, regional assessment tools which may be relevant in a phenotypically diverse disease. We adopted a systematic review and meta-analysis approach to highlight echocardiographic indices that differentiated ARVC patients and healthy controls. Methods: Data was extracted and analysed from prospective trials that employed a case–control design meeting strict inclusion and exclusion as well as a priori quality criteria. Structural indices included proximal RV outflow tract (RVOT1) and RV diastolic area (RVDarea). Functional indices included RV fractional area change (RVFAC), tricuspid annular systolic excursion (TAPSE), peak systolic and early diastolic myocardial velocities (S′ and E′, respectively) and myocardial strain. Results: Patients with ARVC had larger RVOT1 (mean ± s.d.; 34 vs 28 mm, P < 0.001) and RVDarea (23 vs 18 cm2, P < 0.001) compared with healthy controls. ARVC patients also had lower RVFAC (38 vs 46%, P < 0.001), TAPSE (17 vs 23 mm, P < 0.001), S′ (9 vs 12 cm/s, P < 0.001), E′ (9 vs 13 cm/s, P < 0.001) and myocardial strain (−17 vs −30%, P < 0.001). Conclusion: The data from this meta-analysis support current task force criteria for the diagnosis of ARVC. In addition, other RV measures that reflect the complex geometry and function in ARVC clearly differentiated between ARVC and healthy controls and may provide additional diagnostic and management value. We recommend that future working groups consider this data when proposing new/revised criteria for the echocardiographic diagnosis of ARVC.

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.

Aim Left ventricular (LV) transient ischemic dilatation (TID) is not clear how it relates to inducible myocardial ischemia during stress echocardiography (SE). Methods and Results Eighty-eight SEs were examined from the site certification phase of the ISCHEMIA Trial. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured at rest and peak stages and the percent change calculated. Moderate or greater ischemia was defined as ≥3 segments with stress-induced severe hypokinesis or akinesis. Optimum cut points in stress-induced percent EDV and ESV change that identified moderate or greater myocardial ischemia were analyzed. Analysis from percentage distribution identified a > 13% LV volume increase in EDV or a > 9% LV volume increase in ESV as the optimum cutoff points for moderate or greater ischemia. Using these definitions for TID, there were 27 (31%) with TIDESV and 12 (14%) with TIDEDV. By logistic regression analysis and receiver operating characteristic curves, the percent change in ESV had a stronger association with moderate or greater myocardial ischemia than that of EDV change. Compared to those without TIDESV, cases with TIDESV had larger extent of inducible wall-motion abnormalities, lower peak stress LVEF, and higher likelihood of moderate or grater ischemia. For moderate or greater myocardial ischemia detection, TIDESV had a sensitivity of 46%, specificity of 83%, positive predictive value of 70%, and negative predictive value of 64%. Conclusion Transient ischemic dilatation by SE is a marker of extensive myocardial ischemia and can be used as an additional marker of higher risk.

We performed real-time myocardial contrast echocardiography on a patient with cardiac amyloidosis and previous normal coronary angiography presenting with atypical chest pain to assess myocardial blood flow reserve (MBFR). Myocardial contrast echocardiography was performed and flash microbubble destruction and replenishment analysis was used to calculate myocardial blood flow. Dipyridamole was used to achieve hyperemia. MBFR was derived from the ratio of peak myocardial blood flow at hyperemia and rest. The results show a marked reduction in MBFR in our patient. Previous reports of luminal obstruction of intramyocardial rather than epicardial vessels by amyloid deposition may be causing microvascular dysfunction.

Noninvasive cardiac imaging has an important role in the assessment of patients with acute-onset chest pain. In patients with suspected acute coronary syndrome (ACS), cardiac imaging offers incremental value over routine clinical assessment, the electrocardiogram, and blood biomarkers of myocardial injury, to confirm or refute the diagnosis of coronary artery disease and to assess future cardiovascular risk. This Review covers the current guidelines and clinical use of the common noninvasive imaging techniques, including echocardiography and stress echocardiography, computed tomography coronary angiography, myocardial perfusion scintigraphy, positron emission tomography, and cardiovascular magnetic resonance imaging, in patients with suspected ACS, and provides an update on the developments in noninvasive imaging techniques in the past 5 years.

Stress echocardiography (SE) is an established tool not only for the assessment of coronary artery disease (CAD), but also for the evaluation of valvular disease and cardiomyopathy. New techniques, namely contrast echocardiography for function and perfusion including assessment of coronary flow reserve, strain imaging, 3-dimensional echocardiography, Doppler-derived coronary flow reserve and multimodality echocardiography, have been incorporated into stress protocols for improving assessment of cardiac disease. In this review, the advantages and disadvantages of these novel SE techniques are examined in terms of feasibility, accuracy, reproducibility and applications.

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

While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.CCTA and angina assessment.Sex differences in stress test, CCTA findings, and symptom severity.Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.ClinicalTrials.gov Identifier: NCT01471522.

The extent and severity of coronary artery disease (CAD), ischemia and angina may influence revascularization decision making, so their inter-relationship is clinically relevant. We used proportional odds models to examine these associations at baseline in 4050 enrolled ischemia trial participants

Nitroxyl (HNO) causes post-translational modification of thiol proteins. In animal models, the HNO donor BMS-986231 causes vasodilation and has inotropic and lusitropic actions. We compared the effects of BMS-986231 to nitroglycerin (NTG) or placebo on cardiac performance in patients with chronic

Sex differences in ischemia, coronary anatomy and symptoms have not been investigated among patients who have moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary CT angiography (CCTA) was required to have obstructive CAD to undergo randomization. We describe sex

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

Transvalvular flow rate (FR), which is stroke volume divided by left ventricular ejection time (in milliliters per second), is physiologically likely to be a better marker of transvalvular flow in patients with severe aortic stenosis (AS) compared with stroke volume index (SVi), a traditional marker

Background The ischemic consequences of coronary artery stenosis can be assessed by invasive fractional flow reserve (FFR) or by noninvasive imaging. We sought to determine (1) the concordance between wall thickening assessment during clinically indicated stress echocardiography (SE) and FFR measurements and (2) the factors associated with hard events in these patients. Methods Two hundred twenty-three consecutive patients who underwent SE and invasive FFR measurements in close succession were analyzed retrospectively for diagnostic concordance and clinical outcomes. Results At the vessel level, the sensitivity, specificity, positive predictive value, and negative predictive value of SE for identifying significant disease as assessed by FFR was 68%, 75%, 43%, and 89%, respectively. The greatest discordance was seen in patients with wall thickening abnormalities (WTAs) and negative FFR. During a follow-up of 3.6 ± 2.2 years, there were 23 cardiovascular (CV) events (death and nonfatal myocardial infarction). The number of wall segments with inducible WTAs emerged as the strongest factor associated with CV events (hazard ratio, 1.18 [1.05-1.34]; P = .008). FFR was not associated with outcome. There was a significant increase in event rate in patients with WTA/negative FFR versus no WTA/negative FFR ( P = .01), but no significant difference versus WTA/positive FFR ( P = .85). Conclusions In a patient population with significant CV risk factors, a normal SE had a high negative predictive value for excluding abnormal FFR. WTAs were associated with outcomes regardless of FFR value, suggesting that this is a superior marker of ischemia to FFR.

Contrast echocardiography is widely used in cardiology. It is applied to improve image quality, reader confidence and reproducibility both for assessing left ventricular (LV) structure and function at rest and for assessing global and regional function in stress echocardiography. The use of contrast in echocardiography has now extended beyond cardiac structure and function assessment to evaluation of perfusion both of the myocardium and of the intracardiac structures. Safety of contrast agents have now been addressed in large patient population and these studies clearly established its excellent safety profile. This document, based on clinical trials, randomized and multicentre studies and published clinical experience, has established clear recommendations for the use of contrast in various clinical conditions with evidence-based protocols.

Stress echocardiography (SE) is a well-established technique for the diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). This review article summarizes the status of SE in CAD, including testing protocols, clinical efficacy and current use of newer technologies: myocardial perfusion, strain imaging, three-dimensional echocardiography and adjunctive carotid ultrasonography. Recent major findings in SE include the clinical value of myocardial perfusion imaging in multicentre studies, as well as when added to left ventricular (LV) wall motion assessment in clinical service. Additionally, SE has been shown to be more cost-effective than exercise ECG in patients with low-intermediate pre-test probability of CAD. Adjunctive atherosclerosis imaging by carotid ultrasonography (CU) to ischaemia testing by SE provides synergistic prognostic value, equivalent to hybrid imaging by PET-CT. Despite the development of newer and more expensive imaging modalities, SE remains the cornerstone for the assessment of CAD and has excellent clinical efficacy, is safe and is cost-effective.

Background Single-photon emission computed tomography (SPECT) is a well-established method to evaluate patients with coronary artery disease. Myocardial contrast echocardiography (MCE) is an imaging technique that allows the assessment of myocardial perfusion in real time. Previous research has shown that vasodilator MCE is superior to SPECT for the prediction of hard events. The aim of this study was to investigate the long-term association of SPECT and MCE with clinical outcomes in patients with known or suspected coronary artery disease. Methods Accordingly, 258 patients who underwent MCE and SPECT as part of multicenter studies performed prospectively were followed up for hard events (all-cause mortality and nonfatal myocardial infarction). The mean age was 63.4 ± 5.5 years, 186 (72.1%) were men, and 32 (12.4%) had left ventricular systolic dysfunction. We calculated the ratio of the number of abnormal segments (at rest and/or stress) to the total number of segments expressed as MCE and SPECT indices. Results Over a mean follow-up period of 80.4 ± 6.1 months, 46 patients had hard events. MCE and SPECT indices were associated with all-cause mortality on univariate analysis ( P = .008 and P = .035, respectively) but only MCE index was independently associated with hard events (hazard ratio, 4.24; 95% CI, 1.27–14.15; P = .019), beyond clinical data and left ventricular function, and independently associated with hard cardiac events (hazard ratio, 4.78; 95% CI, 1.06–21.59; P = .042). Conclusions MCE but not SPECT showed a long-term association with outcome. These results thus favor the routine use of MCE in the long-term assessment of patients with known or suspected coronary artery disease.

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.

Objectives We hypothesised that stress echocardiography (SE), may be superior to exercise ECG (ExECG), for predicting CAD and outcome, and cost-beneficial, when performed as initial investigation in newly suspected angina. Methods All patients seen in 2011, with suspected angina, no history of CAD, pre-test likelihood of CAD of > 10% and who underwent SE or ExECG as first line were identified retrospectively. Cost to diagnosis was calculated by adding the cost of all tests, up to and including coronary angiography (CA), on an intention-to-treat basis. Follow-up data on cardiac death and myocardial infarction (MI) were collected, 26 months after the presentation of the last study patient. Results A total of 456 patients underwent ExECG (224 (49%) negative, 93 (20%) positive, 139 (31%) inconclusive) and 241 underwent SE (200 (83%) negative, 35 (15%) positive, 6 (2%) inconclusive) as first line. In patients subsequently undergoing CA, CAD was present in 46% (37/80) of patients with positive ExECG vs. 72% (23/32) patients with positive SE (p = 0.01). Mean cost to diagnosis was £456 for the ExECG vs. £360 for the SE group (p = 0.002). Over a mean follow-up period of 31 ± 5 months, cardiac events were 2% each in negative SE vs. negative ExECG (p = 0.9). Conclusions SE is superior to ExECG for prediction of CAD and is cost-beneficial when used as initial test in patients with no history of CAD presenting with suspected angina.

A 79-year-old man presented with increasing breathlessness and his echocardiogram revealed severe left ventricular systolic dysfunction and low-flow low-gradient aortic stenosis. Low-dose dobutamine stress echocardiography revealed the absence of contractile reserve (increase of stroke volume by ≥20% did not occur). The test would have therefore been inconclusive. However, the attainment of normal flow (FR≥200 mL/s) during dobutamine stress enabled the diagnosis of true severe aortic stenosis.