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Background and Aims: The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF., Methods: Strain sUrveillance during Chemotherapy for improving Cardiovascular Outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites. Of 355 patients receiving anthracyclines with normal baseline LVEF, 333 patients (age 59±13 years, 79% women) with at least one other CTRCD risk factor, able to undergo magnetic resonance imaging (MRI), GLS and 3D echocardiography were tracked over 12 months. A total of 105 patients (age 59±13 years, 75% women, 69% breast cancer) developing GLS-CTRCD (>12% relative reduction of GLS without a change in LVEF) between cardioprotection with neurohormonal antagonists versus usual care were randomized. The primary endpoint was 12-month change in MRI-LVEF; the secondary endpoint was MRI LVEF-defined CTRCD., Results: During follow-up, 2 patients died and 2 developed heart failure. Most patients were randomized at 3 months (62%). Median doses of angiotensin inhibition/blockade and beta-blockade were 75% and 50% of respective targets; 21 (43%) had side-effects attributed to cardioprotection. Due to a smaller LVEF change from baseline with cardioprotection than usual care (-2.5±5.4% vs -5.6±5.9%, p=0.009), follow-up LVEF was higher after cardioprotection (59±5% vs 55±6%, p<0.0001). After adjustment for baseline LVEF, the mean (95% confidence interval) difference in the change in LVEF between the two groups was -3.6% (-1.8% to -5.5%, p<0.001). After cardioprotection, 1/49 patients developed 12-month LVEF-CTRCD, compared to 6/56 in usual care (p=0.075). GLS improved at 3 months post-randomization in the cardioprotection group, with little change with usual care., Conclusions: In patients with isolated GLS reduction after anthracyclines, cardioprotection is associated with better preservation of 12-month MRI-LVEF compared with usual care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Helping people to understand their cardiovascular (CV) risk can influence the choices they make for risk reduction, including medication adherence and lifestyle modification. This study sought whether repeated visualization of coronary artery calcium (CAC) images was effective in sustaining long-term risk control in primary prevention, independent of a risk reduction program., Methods: Asymptomatic, statin-naïve participants, 40-70 years, with a family history of premature coronary artery disease and a CAC score from 1-400 were randomised to a nurse-led CV risk reduction program or standard care with bi-annual reviews. Only the intervention group (220 of 449 participants) visualised their CAC image (with repeat exposure in the first 3 months) and were initiated on statin therapy. The primary outcome was change in Framingham Risk Score (FRS) at 36 months, and the impact of CAC image recall on CV risk was assessed., Results: The reduction in FRS (difference in differences (DID): -3.4% [95%CI: -4.4% to -2.4%], p=<0.001 and low-density-lipoprotein-cholesterol -1.2mmol/L [95%CI: -1.4 to -1.0], p=<0.001)) over 36 months was greater in the intervention than the control group. Within the intervention group, sustained recall of CAC images at 24 months was associated with lower systolic blood pressure (DID -4.3mmHg [95%CI: -7.7 to-0.9], p=0.01) and waist circumference (DID -2.0cm [95% CI: -3.9 to -0.1], p=0.03) at 36 months compared to unsustained recall., Conclusion: A nurse-led program, combining personalized patient visualization of CAC imaging with statin therapy, is beneficial for improving CV risk. Recalling the presentation of CAC images through repeated visual exposure may influence risk reduction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Heart failure is a highly heterogeneous disease, and genetic testing may allow phenotypic distinctions that are incremental to those obtainable from imaging. Advances in genetic testing have allowed for the identification of deleterious variants in patients with specific heart failure phenotypes (dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and hypertrophic cardiomyopathy), and many of these have specific treatment implications. The diagnostic yield of genetic testing in heart failure is modest, and many rare variants are associated with incomplete penetrance and variable expressivity. Environmental factors and co-morbidities have a large role in the heterogeneity of the heart failure phenotype. Future endeavours should concentrate on the cumulative impact of genetic polymorphisms in the development of heart failure., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD., Methods: In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP)., Results: We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13-27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06-0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events., Conclusions: In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes., Trial Registration: NCT03186404., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Arterial hypertension remains the most frequent cardiovascular (CV) risk factor, and is responsible for a huge global burden of disease. Echocardiography is the first-line imaging method for the evaluation of cardiac damage in hypertensive patients and novel techniques, such as 2D and D speckle tracking and myocardial work, provide insight in subclinical left ventricular (LV) impairment that would not be possible to detect with conventional echocardiography. The structural, functional, and mechanical cardiac remodelling that are detected with imaging are intermediate stages in the genesis of CV events, and initiation or intensification of antihypertensive therapy in response to these findings may prevent or delay progressive remodelling and CV events. However, LV remodelling-especially LV hypertrophy-is not specific to hypertensive heart disease (HHD) and there are circumstances when other causes of hypertrophy such as athlete heart, aortic stenosis, or different cardiomyopathies need exclusion. Tissue characterization obtained by LV strain, cardiac magnetic resonance, or computed tomography might significantly help in the distinction of different LV phenotypes, as well as being sensitive to subclinical disease. Selective use of multimodality imaging may therefore improve the detection of HHD and guide treatment to avoid disease progression. The current review summarizes the advanced imaging tests that provide morphological and functional data about the hypertensive cardiac injury., Competing Interests: Conflict of interest: M.T. and C.C. declare no conflict of interest related to this article or unrelated to this article. T.H.M.’s institution receives grants from GE Medical Systems, Astra Zeneca, Applied Therapeutics, National Health and Medical Research Council (Australia), and Medical Research Future Fund (Australia)., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Heart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target for reducing incident HF in DM. Left ventricular (LV) dysfunction secondary to DM is heterogeneous, with phenotypes including predominantly systolic, predominantly diastolic, and mixed dysfunction. Indeed, the pathogenesis of HF in this setting is heterogeneous. Effective management of this problem will require detailed phenotyping of the contributions of fibrosis, microcirculatory disturbance, abnormal metabolism, and sympathetic innervation, among other mechanisms. For this reason, an imaging strategy for the detection of HF risk needs to not only detect subclinical LV dysfunction (LVD) but also characterize its pathogenesis. At present, it is possible to identify individuals with DM at increased risk HF, and there is evidence that cardioprotection may be of benefit. However, there is insufficient justification for HF screening, because we need stronger evidence of the links between the detection of LVD, treatment, and improved outcome. This review discusses the options for screening for LVD, the potential means of identifying the underlying mechanisms, and the pathways to treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Left atrial imaging and detailed knowledge of its pathophysiology, especially in the context of heart failure, have become an increasingly important clinical and research focus. This development has been accelerated by the growth of non-invasive imaging modalities, advanced image processing techniques, such as strain imaging, and the parallel emergence of catheter-based left atrial interventions like pulmonary vein ablation, left atrial appendage occlusion, and others. In this review, we focus on novel imaging methods for the left atrium, their pathophysiological background, and their clinical relevance for various cardiac conditions and diseases., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Effective and efficient education and patient engagement are fundamental to improve health outcomes in heart failure (HF). The use of artificial intelligence (AI) to enable more effective delivery of education is becoming more widespread for a range of chronic conditions. We sought to determine whether an avatar-based HF-app could improve outcomes by enhancing HF knowledge and improving patient quality of life and self-care behaviour., Methods and Results: In a randomized controlled trial of patients admitted for acute decompensated HF (ADHF), patients at high risk (≥33%) for 30-day hospital readmission and/or death were randomized to usual care or training with the HF-app. From August 2019 up until December 2020, 200 patients admitted to the hospital for ADHF were enrolled in the Risk-HF study. Of the 72 at high-risk, 36 (25 men; median age 81.5 years; 9.5 years of education; 15 in NYHA Class III at discharge) were randomized into the intervention arm and were offered education involving an HF-app. Whilst 26 (72%) could not use the HF-app, younger patients [odds ratio (OR) 0.89, 95% confidence interval (CI) 0.82-0.97; P <  0.01] and those with a higher education level (OR 1.58, 95% CI 1.09-2.28; P =  0.03) were more likely to enrol. Of those enrolled, only 2 of 10 patients engaged and completed ≥70% of the program, and 6 of the remaining 8 who did not engage were readmitted., Conclusions: Although AI-based education is promising in chronic conditions, our study provides a note of caution about the barriers to enrolment in critically ill, post-acute, and elderly patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: We investigated the effects of exposure to very low levels of particulate matter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) on coronary calcium score (CCS) in asymptomatic adults who are free of coronary artery disease (CAD)., Methods and Results: This study included 606 asymptomatic adults (49% men, aged 56±7 years) recruited from communities in three states of Australia during 2017-2018. CCS was measured using coronary computed tomography scan at recruitment. Annual PM2.5 and NO2 concentrations were estimated on the year before recruitment using statistical exposure models and assigned to each participant's residential address. Medical history, physical measurements, biochemistry, and sociodemographic and socioeconomic status were also recorded. Median concentrations of PM2.5 and NO2 were 6.9 µg/m3 [interquartile range (IQR) 6.0-7.7)] and 3.1 ppb [IQR 2.2-4.5], respectively. Of the 606 participants, 16% had high CCS (≥100) and 4% had very high CCS (≥400). Exposure to higher PM2.5 (per µg/m3) was significantly associated with greater odds of having high CCS (OR 1.20, 95% CI 1.02-1.43) and very high CCS (OR 1.55, 95% CI 1.05-2.29). Similar associations were observed for NO2 and high CCS (OR 1.14, 95% CI 1.02-1.27) and very high CCS (OR 1.23, 95% CI 1.07-1.51). These findings were robust to adjustment for sociodemographic factors, traditional cardiovascular risk factors, renal function, education, and socio-economic status., Conclusions: Ambient air pollution even at low concentration was associated with degree of coronary artery calcification among asymptomatic low cardiovascular risk adults, independent of other risk factors. These findings suggest that air pollution is one of the residual risk factors of CAD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Left atrial (LA) strain is a prognostic biomarker with utility across a spectrum of acute and chronic cardiovascular pathologies. There are limited data on intervendor differences and no data on intermodality differences for LA strain. We sought to compare the intervendor and intermodality differences between transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) derived LA strain. We hypothesized that various components of atrial strain would show good intervendor and intermodality correlation but that there would be systematic differences between vendors and modalities., Methods and Results: We evaluated 54 subjects (43 patients with a clinical indication for CMR and 11 healthy volunteers) in a study comparing TTE- and CMR-derived LA reservoir strain (ƐR), conduit strain (ƐCD), and contractile strain (ƐCT). The LA strain components were evaluated using four dedicated types of post-processing software. We evaluated the correlation and systematic bias between modalities and within each modality. Intervendor and intermodality correlation was: ƐR [intraclass correlation coefficient (ICC 0.64-0.90)], ƐCD (ICC 0.62-0.89), and ƐCT (ICC 0.58-0.77). There was evidence of systematic bias between vendors and modalities with mean differences ranging from (3.1-12.2%) for ƐR, ƐCD (1.6-8.6%), and ƐCT (0.3-3.6%). Reproducibility analysis revealed intraobserver coefficient of variance (COV) of 6.5-14.6% and interobserver COV of 9.9-18.7%., Conclusion: Vendor derived ƐR, ƐCD, and ƐCT demonstrates modest to excellent intervendor and intermodality correlation depending on strain component examined. There are systematic differences in measurements depending on modality and vendor. These differences may be addressed by future studies, which, examine calibration of LA geometry/higher frame rate imaging, semi-quantitative approaches, and improvements in reproducibility., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Although both left atrial (LA) and ventricular (LV) dysfunction has been accepted as an important risk factor of atrial fibrillation (AF), usefulness of LA and LV strain has not been fully compared for prediction of AF. The aims of this study were to clarify the associations of both LA and LV strain with AF and to compare their predictive values in the risk stratification for AF., Methods and Results: We evaluated 531 consecutive patients (median age 67 years, 56% male), with no history of AF who underwent echocardiography after cryptogenic stroke. Standard echocardiographic parameters were measured, and speckle-tracking was used to measure LA (reservoir, pump, and conduit strain) and LV strain (global longitudinal strain, GLS). The baseline clinical and echocardiographic parameters of the patients who developed AF and those who did not were compared. Median 36 months of follow-up, 61 patients (11%) had newly diagnosed AF. LA pump strain and GLS were significantly and independently associated with AF and provided incremental predictive value over clinical and standard echocardiographic parameters. Areas under the receiver-operating curves for GLS (0.841) were comparable to LA pump (0.825) and reservoir (0.851) strain. However, predictive value of both strains was different between patients with and without LA enlargement at the time of transthoracic echocardiography screening. LA strain was more useful than LV strain in patients with normal LA volumes, while LV strain was more useful than LA strain in patients with abnormal LA volumes., Conclusion: Both LA and LV strain are significantly and independently associated with AF and provide incremental predictive value over clinical and standard echocardiographic parameters. However, priorities of strain assessment are different depends on patients' condition at the time of echocardiography., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Improvement in left ventricular (LV) systolic reserve, including exertional increase in global longitudinal strain (GLS), may contribute to the clinical benefit from therapeutic interventions in heart failure with preserved ejection fraction (HFpEF). However, GLS is an afterload-dependent parameter, and its measurements may not adequately reflect myocardial contractility recruitment with exercise. The estimation of myocardial work (MW) allows correction of GLS for changing afterload. We sought to investigate the associations of GLS and MW parameters with the response of exercise capacity to spironolactone in HFpEF., Methods and Results: We analysed 114 patients (67 ± 8 years) participating in the STRUCTURE study (57 randomized to spironolactone and 57 to placebo). Resting and immediately post-exercise echocardiograms were performed at baseline and at 6-month follow-up. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. The amelioration of exercise intolerance at follow-up in the spironolactone group was accompanied by a significant improvement in exertional increase in GCW (P = 0.002) but not in GLS and other MW parameters. Increase in exercise capacity at 6 months was independently correlated with change in exertional increase in GCW from baseline to follow-up (β = 0.24; P = 0.009) but not with GLS (P = 0.14); however, no significant interaction with the use of spironolactone on peak VO2 was found (P = 0.97)., Conclusion: GCW as a measure of LV contractile response to exertion is a better determinant of exercise capacity in HFpEF than GLS. Improvement in functional capacity during follow-up is associated with improvement in exertional increment of GCW., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: To develop a cost-effectiveness model to address the outcome and economic implications of different thresholds for surgery in the management of aortopathy associated with bicuspid aortic valve disease., Methods and Results: A model was created from the perspective of an Australian healthcare funding agency. The index case was a 65-year-old with bicuspid aortic valve (BAV) and ascending aorta diameter of 5.0 cm. Health states were defined as: pre-operative with dilated aorta, post-operative without complications, post-complication, and death. The mean and variance of risks and transition probabilities were taken from a local surgical database and local costs and utilities of elective and urgent thoracic aortic surgery (AoS) with or without aortic valve replacement, with a sensitivity analysis based on a systematic review. Scenario analyses were provided for other aortic dimensions. Implications for survival, quality-adjusted life years (QALYs), and costs were calculated from healthcare delivery and economic perspectives. After 10 000 simulations for the reference case, the utility of watchful waiting (WW) exceeded that of elective AoS (13 ± 4 vs. 10 ± 5 QALY). The net monetary benefit was A$351 063 ± 304 965 with immediate AoS vs. 534 797 ± 198 570 with WW surveillance. The most important variables affecting effectiveness were utility value of survivors, rate of aortic growth, and probability of acute aortic event during WW., Conclusions: This decision-analytic model informed by our practice, as well as a systematic analysis, shows that AoS in a BAV patient with aorta <5 cm diameter is costlier and less effective than WW., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Socioeconomic status (SES) is recognizably linked with incident heart failure (HF) risk and the association of SES with geography presents a potential target for geographical location of preventive health services. To better inform policy we sought to quantify the independent association between SES and incident HF and investigate differences by type of SES measure., Methods and Results: MEDLINE and EMBASE were searched up to August 2018. Observational studies and randomized trials reporting adjusted HF incidence by stratified socioeconomic measures were included. Effect sizes reflected HF incidence in the lowest vs. highest SES stratum and were pooled using a random-effects model. Low SES referred to the lowest resource stratum, the definition of which varied across studies: meta-analysis was only performed where strata were comparable. Statistical heterogeneity was assessed using the I2 statistic. Eleven studies comprising 6 308 006 individuals and 104 217 HF events found that low SES was associated with an increase in risk of incident HF ranging between 43% and 87% depending on SES measure, with an overall estimate of 62% [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.50-1.76]. By individual measure, HRs of 1.66 (95% CI 1.3-2.11), 1.87 (95% CI 1.33-2.62), and 1.54 (95% CI 1.22-1.95) were observed for education, income, and occupation, respectively. For area-level indexes, HRs were 1.43 (95% CI 1.2-1.69) (Carstairs index) and 1.61 (95% CI 1.56-1.65) (index of multiple deprivation)., Conclusion: Low SES assessed by all common measures confers independent risk for incident HF. These findings carry implications for the design and delivery of HF prevention programmes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aims: In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM., Methods and Results: We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003)., Conclusions: In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.

Aims: Impairment of myocardial function is an important potential complication of systemic sclerosis (SSc) and associated with poor prognosis. The detection of left (LV) and right ventricular (RV) dysfunction may prompt specific therapeutic interventions. We sought to investigate the prognostic value of both LV and RV deformation in patients with SSc., Methods and Results: Speckle tracking LV strain parameters [global longitudinal strain (GLS) and global circumferential strain (GCS)] and tricuspid annular peak systolic velocity (Ts') were measured in 103 patients with SSc and 103 age- and gender-matched controls. Subjects were followed for a median of 3.4 years for heart failure-specific admission or death, and the association of the study parameters with outcome was assessed using Cox proportional hazards models. GLS, GCS, and Ts' were significantly impaired in patients with SSc, even without pulmonary hypertension, compared with controls. GCS (r2 = 0.07, P = 0.03) but not GLS (r2 = 0.04, P = 0.11) was associated with systolic pulmonary artery pressure. During follow-up, SSc patients (n = 17, 17%) had more events than controls (n = 7, 7%, P = 0.04). In SSc patients, GCS (but not GLS), Ts', and 6-minute walk distance (6MWD) were significantly associated with outcome. 6MWD and Ts' (but not GCS) were independently associated with outcome. A model based on age, gender, 6MWD, and GCS was significantly improved by adding by adding Ts' (P = 0.02)., Conclusion: RV dysfunction was associated with adverse outcome, independent of and incremental to clinical and LV deformation parameters in SSc. LV dysfunction appears to have less prognostic relevance than RV dysfunction.

Aims: Appropriate Use Criteria (AUC) for echocardiography were developed in 2007 to facilitate decision-making, reduce variability in test utilization, and encourage rational use of imaging. However, there is little evidence that the AUC have favourably influenced ordering behaviour. This study explores the factors that contribute to clinicians requesting echocardiograms with a focus on appropriate use., Methods and Results: Semi-structured face-to-face interviews with cardiologists and non-cardiologists who had requested echocardiograms were conducted at an Australian tertiary hospital. The interview guide included hypothetical clinical scenarios to better understand decision-making in ordering echocardiograms and the actions they could take when receiving test reports. Interviews underwent thematic analysis. Seventeen clinicians were interviewed, ten of whom were cardiologists. All participants ordered echocardiograms to support their clinical decision-making. Awareness of the AUC was low. The categorization of tests as 'appropriate' or 'inappropriate' was considered ineffective as it failed to reflect the decision-making process. The decision to request echocardiograms was influenced by a number of personal and systemic factors as well as guidelines and protocols. Training and experience, patients' expectations, and management of uncertainty were key personal factors. Systemic factors involved the accessibility of services and health insurance status of the patient., Conclusion: Factors that influenced the ordering of echocardiograms by clinicians at a tertiary care hospital did not appear to be amenable to control with AUC. Alternative approaches may be more effective than the AUC in addressing the overuse of echocardiography., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: Load dependence is an important source of variation in left ventricular (LV) deformation. This impacts on the precision of information obtained from serial measurements. However, it is clinically important to distinguish actual myocardial dysfunction from changes associated with altered loading conditions. We sought to investigate the association of changes of loading parameters with changes in LV longitudinal (GLS) and circumferential (GCS) strains., Methods and Results: Baseline and a 12-month follow-up 2D echocardiograms were performed in 191 Stage A heart failure patients with uncomplicated hypertension. These patients underwent simultaneous measurement of conventional and central blood pressures (BPs) and haemodynamic measurements by applanation tonometry. Significant, but weak correlations (r = 0.15-0.28) of LV strain parameters and their changes over the follow-up period were shown for the majority of LV afterload-associated variables, including central and brachial systolic, diastolic, and mean BPs; 24-h systolic and diastolic BPs; peak reservoir and excess pressures; central augmented pressure (CAP) and pulse pressure; augmentation index; and arterial elastance index (EaI). Central mean BP, EaI, and changes in CAP and EaI over follow-up were independent contributors to LV deformation in multivariable analysis. No improvement in the Bland-Altman 95% limits of agreement and correlation coefficients was seen with LV afterload correction of GLS and GCS using central BP indices., Conclusions: LV longitudinal and circumferential strains in a population without apparent heart disease is relatively insusceptible to changes in LV afterload within physiological range, which, therefore, seem unlikely to be a significant confounder in repeated GLS or GCS observations., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aims: Left atrial (LA) function helps to preserve cardiac output and to control pulmonary capillary wedge pressure in the setting of left ventricular (LV) impairment, but little is known about the contribution of the LA function to ventricular arrhythmia. We sought whether LA booster pump function was associated with arrhythmias in patients undergoing primary prevention implantable cardioverter-defibrillator (ICD) implantation for non-ischaemic dilated cardiomyopathy (NICM), independent of global longitudinal strain (GLS) and mechanical dispersion (MD)., Methods and Results: We identified 124 NICM patients (56 ± 13, 67 male) who underwent echocardiography pre-ICD implantation for primary prevention. The main outcome measure was appropriate ICD therapy (anti-tachycardia pacing or shock). The mitral A-wave was used as an LA functional marker. MD was defined as standard deviation of time to peak strain of each segment. Over a median follow-up of 3.8 ± 2.2 years, 36 patients had appropriate ICD therapy, including 23 shocks. Patients with appropriate ICD therapy had lower A-wave velocity (P < 0.001), larger LA volume (P < 0.001), and impaired circumferential MD (P = 0.006), but similar ejection fraction (EF) (P = 0.40) and GLS (P = 0.11). In sequential Cox proportional hazards models, A-wave, E/A ratio, and GLS were significantly associated with outcomes, independent of age, sex, and cardiac resynchronization therapy defibrillator or left bundle branch block. In nested Cox models, mitral A-wave had a prognostic value incremental to models with LV systolic (EF and GLS) and diastolic functional parameters (E/A, E/e', and LA volume) and MD., Conclusion: LA booster pump function was an independent and incremental predictor of arrhythmias in NICM over GLS and MD, and may aid better risk stratification in this population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Central blood pressure (CBP) independently predicts cardiovascular risk, but calibration methods may affect accuracy of central systolic blood pressure (CSBP). Standard central systolic blood pressure (Stan-CSBP) from peripheral waveforms is usually derived with calibration using brachial SBP and diastolic BP (DBP). However, calibration using oscillometric mean arterial pressure (MAP) and DBP (MAP-CSBP) is purported to provide more accurate representation of true invasive CSBP. This study sought to determine which derived CSBP could more accurately discriminate cardiac structural abnormalities., Methods: A total of 349 community-based patients with risk factors (71±5years, 161 males) had CSBP measured by brachial oscillometry (Mobil-O-Graph, IEM GmbH, Stolberg, Germany) using 2 calibration methods: MAP-CSBP and Stan-CSBP. Left ventricular hypertrophy (LVH) and left atrial dilatation (LAD) were measured based on standard guidelines., Results: MAP-CSBP was higher than Stan-CSBP (149±20 vs. 128±15mm Hg, P < 0.0001). Although they were modestly correlated (rho = 0.74, P < 0.001), the Bland-Altman plot demonstrated a large bias (21mm Hg) and limits of agreement (24mm Hg). In receiver operating characteristic (ROC) curve analyses, MAP-CSBP significantly better discriminated LVH compared with Stan-CSBP (area under the curve (AUC) 0.66 vs. 0.59, P = 0.0063) and brachial SBP (0.62, P = 0.027). Continuous net reclassification improvement (NRI) (P < 0.001) and integrated discrimination improvement (IDI) (P < 0.001) corroborated superior discrimination of LVH by MAP-CSBP. Similarly, MAP-CSBP better distinguished LAD than Stan-CSBP (AUC 0.63 vs. 0.56, P = 0.005) and conventional brachial SBP (0.58, P = 0.006), whereas Stan-CSBP provided no better discrimination than conventional brachial BP (P = 0.09)., Conclusions: CSBP is calibration dependent and when oscillometric MAP and DBP are used, the derived CSBP is a better discriminator for cardiac structural abnormalities., (© American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Central blood pressure (BP) is an acknowledged contributor to end-organ damage and independent determinant of prognosis. Primary analysis from the BPGUIDE study demonstrated no detriment on left ventricular (LV) structure from central BP-guided hypertension management, despite significant medication withdrawal. However, the effect of this on LV function has not been investigated. In this study, we sought to investigate the impact of central BP-guided hypertension management on LV systolic and diastolic performance., Methods: A total of 286 enrollees with uncomplicated hypertension were randomized to therapeutic decisions guided by best-practice usual care (UC) or, in addition, by central BP intervention (CBP) for 12 months. Each participant underwent baseline and follow-up 2-dimensional echocardiography, with assessment undertaken by an expert blinded to participant allocation., Results: Antihypertensive medication quantity remained unchanged for UC but significantly decreased with intervention. However, no significant between-group differences were noted for changes during follow-up in both brachial and central BP, as well as other central hemodynamic parameters: augmentation index and augmented pressure. Similarly, there were no differences between groups in parameters of LV diastolic function: tissue e' velocity (∆UC vs. ∆CBP; P = 0.27) and E/e' ratio (∆UC vs. ∆CBP; P = 0.60), and systolic parameters: LV longitudinal strain (∆UC vs. ∆CBP; P = 0.55), circumferential strain (∆UC vs. ∆CBP; P = 0.79), and ejection fraction (∆UC vs. ∆CBP; P = 0.15)., Conclusions: Hypertension management guided by central BP, resulting in significant withdrawal of medication to maintain appropriate BP control, had no adverse effect on LV systolic or diastolic function. Clinical trials registration: Australia New Zealand Clinical Trial Registry Number ACTRN12608 000041358., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., (Published on behalf of the European Society of Cardiology. This article has been co-published in the Journal of the American Society of Echocardiography. All rights reserved. © The Author 2015.)

Aim: Chronic right ventricle (RV) apical (RVA) pacing is standard treatment for an atrioventricular (AV) block but may be deleterious to left ventricle (LV) systolic function. Previous clinical studies of non-apical pacing have produced conflicting results. The aim of this randomized, prospective, international, multicentre trial was to compare change in LV ejection fraction (LVEF) between right ventricular apical and high septal (RVHS) pacing over a 2-year study period., Methods and Results: We randomized 240 patients (age 74 ± 11 years, 67% male) with a high-grade AV block requiring >90% ventricular pacing and preserved baseline LVEF >50%, to receive pacing at the RVA (n = 120) or RVHS (n = 120). At 2 years, LVEF decreased in both the RVA (57 ± 9 to 55 ± 9%, P = 0.047) and the RVHS groups (56 ± 10 to 54 ± 10%, P = 0.0003). However, there was no significant difference in intra-patient change in LVEF between confirmed RVA (n = 85) and RVHS (n = 83) lead position (P = 0.43). There were no significant differences in heart failure hospitalization, mortality, the burden of atrial fibrillation, or plasma brain natriutetic peptide levels between the two groups. A significantly greater time was required to place the lead in the RVHS position (70 ± 25 vs. 56 ± 24 min, P < 0.0001) with longer fluoroscopy times (11 ± 7 vs. 5 ± 4 min, P < 0.0001)., Conclusion: In patients with a high-grade AV block and preserved LV function requiring a high percentage of ventricular pacing, RVHS pacing does not provide a protective effect on left ventricular function over RVA pacing in the first 2 years., Protect-Pace: ClinicalTrials.gov number NCT00461734., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Subclinical diabetic cardiomyopathy (DCM) is frequent in asymptomatic subjects with type 2 diabetes (T2DM). We sought the response of functional and fibrosis markers to therapy in a trial of aldosterone antagonism for treatment of DCM., Methods: Biochemical, anthropometric, and echocardiographic data were measured in 225 subjects with T2DM. Myocardial function was evaluated with standard echocardiography and myocardial deformation; ischaemia was excluded by exercise echocardiography. Calibrated integrated backscatter and post-contrast T1 mapping from cardiac magnetic resonance imaging were used to assess myocardial structure. Amino-terminal propeptides of pro-collagen type I (PINP) and III (PIIINP), the carboxy-terminal propeptide of pro-collagen type I (PICP) and transforming growth factor beta-1 were measured from peripheral blood or urine to assess myocardial collagen turnover., Results: Diastolic dysfunction was identified in 81 individuals, of whom 49 (25 male, age 60 ± 10 years) were randomized to spironolactone 25 mg/day or placebo therapy for 6 months. Groups were well-matched at baseline. Spironolactone therapy was associated with improvements in diastolic filling profile (Δpeak E wave velocity -4 ± 15 vs. 9 ± 10 ms, P = 0.001; ΔE/A ratio -0.1 ± 0.3 vs. 0.2 ± 0.2, P < 0.001) and cIB values (-21.2 ± 4.5 dB vs. -18.0 ± 5.2 dB, P = 0.026; ΔcIB -5.1 ± 6.8 vs. -1.3 ± 5.2, P = 0.030). ΔcIB was independently associated with spironolactone therapy (β = 0.320, P = 0.026) but not Δblood pressure. With intervention, pro-collagen biomarkers (ΔPINP P = 0.92, ΔPICP P = 0.25, ΔPIIINP P = 0.52, and ΔTGF-β1 P = 0.71) and T1 values (P = 0.54) remained similar between groups., Conclusions: Spironolactone-induced changes in myocardial structure and diastolic properties in DCM are small, and are unassociated with changes in collagen biomarkers or T1 values., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: The variability of ejection fraction (EF) poses a problem in the assessment of left ventricular (LV) function in patients receiving potentially cardiotoxic chemotherapy. We sought to use global longitudinal strain (GLS) to compare LV responses to various cardiotoxic chemotherapy regimens and to examine the response to cardioprotection with beta-blockers (BB) in patients showing subclinical myocardial damage., Methods and Results: We studied 159 patients (49 ± 14 year, 127 women) receiving anthracycline (group A, n = 53, 46 ± 17 year), trastuzumab (group T, n = 61, 53 ± 12 year), or trastuzumab after anthracyclines (group AT, n = 45, 46 ± 9 year). LV indices [ejection fraction (EF), mitral annular systolic velocity, and GLS] were measured at baseline and follow-up (7 ± 7 months). Patients who decreased GLS by ≥11% were followed for another 6 months; initiation of BB was at the discretion of the clinician. Anthracycline dose was similar between group A and group AT (213 ± 118 vs. 216 ± 47 mg/m(2), P = 0.85). Although ΔEF was similar among the groups, attenuation of GLS was the greatest in group AT (group A, 0.7 ± 2.8% shortening; T, 1.1 ± 2.7%; and AT, 2.0 ± 2.3%; P = 0.003, after adjustment). Of 52 patients who decreased GLS by ≥-11%, 24 were treated with BB and 28 were not. GLS improved in BB groups (from -17.6 ± 2.3 to -19.8 ± 2.6%, P < 0.001) but not in non-BB groups (from -18.0 ± 2.0 to -19.0 ± 3.0%, P = 0.08). Effects of BB were similar with all regimens., Conclusions: GLS is an effective parameter for identifying systolic dysfunction (which appears worst with combined anthracycline and trastuzumab therapy) and responds to cardioprotection in patients administered beta-blockers.

Background: Although a hypertensive response to exercise (HRE) is associated with cardiac risk and masked hypertension (MHT), its mechanisms and appropriate treatment remain unclear. We investigated spironolactone as a treatment for abnormal vascular and myocardial stiffness in HRE., Methods: In this randomized, double-blind, placebo-controlled study of 115 patients (54 ± 9 years, 57% men) with an HRE (≥210/105 mm Hg in men; ≥190/105 mm Hg in women) but no prior history of hypertension or myocardial ischemia, MHT prevalence was 40%. Patients were randomized to spironolactone 25mg daily (n = 58) or placebo (n = 57) and underwent evaluation at baseline and 3 months with exercise echocardiography, VO2max, pulse wave velocity (PWV), exercise and central blood pressure (BP), and 24-hour ambulatory BP. Changes in left ventricular mass index (LVMI), Doppler-derived E/em ratio (LV filling pressure), and myocardial strain were assessed., Results: Baseline 24-hour systolic BP (SBP) was 133 ± 10 mm Hg and peak-exercise SBP was 219 ± 16 mm Hg. Peak systolic strain (0.3 ± 3.6% vs. -0.1 ± 3.2, P = 0.56), E/em (-1.1 ± 2.3 vs. -0.6 ± 1.7, P = 0.30), VO(2max) (0.4 ± 4.9 vs. -0.9 ± 4.1 ml/kg/min, P = 0.15), and adjusted PWV did not significantly change with treatment, despite reduction in exercise SBP, 24-hour SBP, and LVMI. The change in exercise E/em was of borderline significance (-0.3 ± 2.4 vs. 0.8 ± 2.8, P = 0.06) and became significant after adjustment for baseline differences (P = 0.01). Patients with higher LVMI significantly increased VO(2max) (1.1 ± 5.6 vs. -2.4 ± 4.4 ml/kg/min, P < 0.05) and reduced exercise E/e(m) (-0.7 ± 2.7 vs. 1.9 ± 2.8, P < 0.05)., Conclusions: In HRE patients without previous hypertension, short-term spironolactone reduced exercise BP, 24-hour ambulatory BP, LVMI, and E/e(m) but did not significantly alter exercise capacity or myocardial strain.

Background: The J-curve relationship between brachial diastolic blood pressure (DBP) and mortality is believed to be mediated through reduced myocardial perfusion. This study aimed to determine the relationship between DBP and subendocardial perfusion in patients with and without coronary artery disease (CAD) and to examine central hemodynamic variables that may explain the risk associated with low DBP (aortic stiffness, central pulse pressure, and augmentation index)., Methods: Brachial DBP and radial tonometry were measured in 134 patients with CAD (aged 76±7years; 69% male), 134 individuals without a prior cardiovascular event (control subjects) (aged 77±2years; 69% male) and 47 patients (aged 63±10years) during dobutamine stress echocardiography. Central hemodynamics and subendocardial viability ratio (SEVR), a marker of subendocardial perfusion, were recorded by tonometry., Results: There was no difference in DBP or SEVR between control subjects and CAD patients (P > 0.05), nor was there a difference in SEVR across quartiles of DBP in CAD patients (P = 0.07) or control subjects (P = 0.14). After adjustment for age and height, associations between DBP and SEVR in control subjects (r = 0.185; P = 0.03) and CAD patients (r = 0.204; P = 0.02) were attenuated (P = 0.07 and P = 0.11, respectively). There were no significant relationships between DBP and central hemodynamics (P > 0.05 for all). At peak dobutamine stress, SEVR was significantly reduced in patients with inducible ischemia vs. those with nonischemic response (84±17 vs. 101±22%; P = 0.01). However, DBP was not significantly different (65±14 vs. 67±15mm Hg; P = 0.32)., Conclusions: Brachial DBP is a poor marker of subendocardial perfusion. The J-curve relationship between DBP and mortality is unlikely attributable to reduced myocardial perfusion or adverse central hemodynamics.

Aims: The diastolic stress test (DST) may facilitate the attribution of exertional dyspnoea to cardiac and non-cardiac diseases. However, there is currently no consensus as to the optimal marker of exertional diastolic dysfunction (DD)-the main alternatives being estimated left ventricular (LV) filling pressure (exercise E/e') and diastolic functional reserve (DFRI). We sought to compare the correlates of these parameters., Methods and Results: DST was performed by adding the measurement of the transmitral (E) and annular (e') velocities to standard exercise echo in 559 consecutive patients without significant rest or exercise mitral regurgitation. Exertional DD was separately defined by post-stress E/e' >13 or DFRI <13.5. Logistic regression was used to identify the correlates of abnormal responses and linear regression was used to identify the contribution of both to exercise capacity. Abnormal exercise E/e' (n = 112, 20%) and DFRI (n = 317, 57%) were modestly associated (κ 0.35, P < 0.0001). In a linear regression, abnormal exercise E/e' (β = -0.19, P < 0.001) and DFRI (β = -0.15, P = 0.001) were associated with exercise capacity, independent of age, body mass index, wall thickness, haemodynamics or abnormal stress results. Logistic regression revealed abnormal exercise E/e' (R(2)= 0.34) to be independently associated with female gender (β = 0.26, 95% CI: 0.11-0.60, P = 0.002), age (β = 1.04, 95% CI: 1.01-1.07, P = 0.01), hypertension (β = 0.35, 95% CI: 0.15-0.80, P = 0.01) and wall thickness (β = 4.3, 95% CI: 1.3-14.1, P = 0.02). The closest association of abnormal DFRI was exercise capacity (β = 0.89, 95% CI: 0.79-1.02, P = 0.09); no other clinical or stress variable was independently associated., Conclusion: Exercise E/e' and DFRI are both associated with exercise capacity, but E/e' is more closely associated with the expected parameters of DD.

Background: The prognostic relevance of a hypertensive response to exercise (HRE) is ill-defined in individuals undergoing exercise stress testing. The study described here was intended to provide a systematic review and meta-analysis of published literature to determine the value of exercise-related blood pressure (BP) (independent of office BP) for predicting cardiovascular (CV) events and mortality., Methods: Online databases were searched for published longitudinal studies reporting exercise-related BP and CV events and mortality rates., Results: We identified for review 12 longitudinal studies with a total of 46,314 individuals without significant coronary artery disease, with total CV event and mortality rates recorded over a mean follow-up of 15.2±4.0 years. After adjustment for age, office BP, and CV risk factors, an HRE at moderate exercise intensity carried a 36% greater rate of CV events and mortality (95% CI, 1.02-1.83, P = 0.039) than that of subjects without an HRE. Additionally, each 10mm Hg increase in systolic BP during exercise at moderate intensity was accompanied by a 4% increase in CV events and mortality, independent of office BP, age, or CV risk factors (95% CI, 1.01-1.07, P = 0.02). Systolic BP at maximal workload was not significantly associated with the outcome of an increased rate of CV, whether analyzed as a categorical (HR=1.49, 95% CI, 0.90-2.46, P = 0.12) or a continuous (HR=1.01, 95% CI, 0.98-1.04, P = 0.53) variable., Conclusions: An HRE at moderate exercise intensity during exercise stress testing is an independent risk factor for CV events and mortality. This highlights the need to determine underlying pathophysiological mechanisms of exercise-induced hypertension.

Aim: To evaluate left atrial (LA) volume and function as assessed by strain and strain rate derived from 2D speckle tracking and their association with diastolic dysfunction (DD) in patients with diabetes mellitus (DM)., Methods and Results: Seventy three patients with DM were compared with age- and gender-matched normal controls; 30 patients with DM alone were compared to those with hypertension (HT) alone. The maximum LA volume, traditional measures of atrial function, 2D strain and strain rate were analysed. The LA indexed volume (LAVI) was larger in DM group than that in normal controls (38.2 ± 9.9 vs. 20.5 ± 4.8 ml/m(2), P< 0.0001), as well as in DM alone compared with hypertensive patients (33.9 ± 10 vs. 25.7 ± 8 ml/m(2), P< 0.0001). Global strain was significantly reduced in the DM group compared with that in normal controls (22.5 ± 8.67 vs. 30.6 ± 8.27%; P< 0.0001) but was similar with HT. There was a weak correlation between LAVI and global strain with increasing grades of DD (r= 0.439, P< 0.0001 and r= - 0.316, P< 0.0001, respectively) in the diabetic group. However, there was no significant difference in LAVI between these groups. A logistic regression analysis for predictors of LAVI demonstrated that only diabetes was a determinant of LAVI. Patients with diabetes showed a significant reduction in global strain compared with normal controls but no difference with increasing grades of diastolic function., Conclusions: LA enlargement in DM is independent of associated HT and diastolic function. LA enlargement is associated with LA dysfunction as evaluated by 2D strain. It is likely that a combination of DD and a diabetic atrial myopathy contribute to LA enlargement in patients with DM.

Aims: Myocardial fibrosis is an important contributor to heterogeneity of left ventricular (LV) dysfunction in the metabolic syndrome (MS). Comparison of strain with calibrated integrated backscatter (cIB) and serological fibrosis markers could provide a means to understand the association of cardiac function with markers of fibrosis., Methods and Results: We studied 172 patients with MS (age 50 ± 13 years) and 61 healthy controls in a prospective, cross-sectional study. Echocardiographic evaluation included myocardial velocities and deformation, and calibrated cIB. Procollagen type III amino-terminal propeptide (PIIINP) and procollagen type I carboxy-terminal propeptide (PICP) were measured from serum. MS patients demonstrated LV systolic and diastolic function, and myocardial echodensity disturbances, as well as elevated serum PIIINP and PICP levels. For most functional variables, calibrated cIB in the basal septum was the strongest determinant of impaired LV performance, independent of higher procollagen levels, LV mass index, age, body mass index, creatinine level, and C-reactive protein. Patients with increased abdominal fat deposit (assessed by the waist-to-hip ratio) presented higher levels of procollagen peptides and septal calibrated cIB, and with more profound LV dysfunction as indicated by lower myocardial deformation and early diastolic velocity, and higher E/e'., Conclusion: Myocardial echodensity is a stronger correlate of LV systolic and diastolic dysfunction in MS, than circulating procollagen peptides. Both fibrosis and LV function abnormalities are increased at a higher waist-to-hip ratio, which might provide a rationale for the implementation of intensified therapy in this subset of patients.

Context: Animal studies have demonstrated that dietary sodium intake is a major influence in the pathogenesis of aldosterone-induced effects in the heart such as left ventricular (LV) hypertrophy and fibrosis. LV hypertrophy is an important predictor for cardiovascular morbidity and mortality., Objective: We aimed to investigate the relationships between aldosterone and dietary salt and LV dimensions in patients with primary aldosteronism (PA)., Design and Participants: This case-control study included 21 patients with confirmed PA and 21 control patients with essential hypertension matched for age, gender, duration of hypertension, and 24-h systolic and diastolic blood pressure., Main Outcome Measures: Patients were evaluated by echocardiography and 24-h urinary sodium (UNa) excretion while consuming their usual diets., Results: Patients with PA had significantly greater mean LV end-diastolic diameter, interventricular septum and posterior wall thicknesses, LV mass (LVM) and LV mass index, and end systolic and diastolic volumes than control patients. UNa significantly positively correlated with interventricular septum, posterior wall thicknesses, and LVM in the patients with PA but not in control patients. In a multivariate analysis, UNa was an independent predictor for LV wall thickness and LV mass among the patients with PA but not in patients with essential hypertension., Conclusions: These findings emphasize the importance of dietary sodium in determining the degree of cardiac damage in those patients with PA, and we suggest that aldosterone excess may play a permissive role. In patients with PA, because a high-salt diet is associated with greater LVM, dietary salt restriction might reduce cardiovascular risk.

Background: A hypertensive response to exercise (HRE; defined as normal clinic blood pressure (BP) and exercise systolic BP (SBP) ≥210 mm Hg in men or ≥190 mm Hg in women, or diastolic BP (DBP) ≥105 mm Hg) independently predicts mortality. The mechanisms remain unclear but may be related to masked hypertension. This study aimed to assess the prevalence of masked hypertension and its association with cardiovascular risk factors, including left ventricular (LV) mass, in patients with a HRE., Methods: Comprehensive clinical and echocardiographic evaluation (including central BP, aortic pulse wave velocity by tonometry) and 24-h ambulatory BP monitoring (ABPM) were performed in 72 untreated patients with HRE (aged 54 ± 9 years; 60% male; free from coronary artery disease confirmed by exercise stress echocardiography). Masked hypertension was defined according to guidelines as daytime ABPM ≥135/85 mm Hg and clinic BP <140/90 mm Hg., Results: Masked hypertension was present in 42 patients (58%). These patients had higher LV mass index (41.5 ± 8.7 g/m(2.7) vs. 35.9 ± 8.5 g/m(2.7); P = 0.01), LV relative wall thickness (RWT; 0.42 ± 0.09 vs. 0.37 ± 0.06; P = 0.004) and exercise SBP (222 ± 17 mm Hg vs. 212 ± 14 mm Hg; P = 0.01), but no significant difference in aortic pulse wave velocity or central pulse pressure (P > 0.05 for both). The strongest independent determinant of LV mass index was the presence of masked hypertension (unstandardized β = 5.6; P = 0.007), which was also independently related to LV RWT (unstandardized β = 0.04; P = 0.03)., Conclusions: Masked hypertension is highly prevalent in HRE patients with a normal resting office BP and is associated with increased LV mass index and RWT. Clinicians should consider measuring ABPM or home BP in HRE patients.

Aims: Previous research has described differences in left ventricular (LV) systolic tissue velocity between genders. This study aimed to determine the association between LV tissue velocity and LV size in healthy controls and in those with type 2 diabetes (T2DM)., Methods and Results: LV tissue velocities were measured in 71 controls and 222 patients with T2DM by pulsed-wave Doppler and colour-coded tissue Doppler (TDI) during systole (S' and S(m)) and diastole (early, E' and E(m), and late, A' and A(m)) at the basal septum and lateral wall. Both systolic tissue velocities were higher in males than in females within controls (S': 7.3 +/- 1.2 vs. 6.6 +/- 1.0 cm/s; P = 0.017, S(m): 6.2 +/- 1.0 vs. 5.5 +/- 0.7 cm/s; P = 0.002) but only by colour-coded TDI in patients with T2DM (S(m): 5.7 +/- 1.7 vs. 4.9 +/- 1.7 cm/s; P = 0.025). Correction for LV length negated the difference between genders in the controls and patients with T2DM (P > 0.05 for all). In controls, LV length was the strongest predictor of S' (beta = 0.393, P = 0.002), whereas height was the strongest predictor of S(m) (beta = 0.394, P = 0.003)., Conclusion: In controls, systolic tissue velocities are significantly higher in males compared with females, which may be explained by the increased chamber size of men.

Echocardiography has become an integral part of modern cardiology, and parameters measured by echocardiography are enshrined in guidelines as components of clinical decision-making in the management of heart failure, valve disease and arrhythmias. This review will explore four modalities which will underpin the future of echocardiography - the hand-held machine, quantification, three-dimensional imaging, and contrast. Finally, we will explore the implications of the new financial milieu for the selection of cardiac imaging modalities.

Aims: To determine if perfusion stress echocardiography (PSE) with Imagify (perflubutane polymer microspheres) is comparable to stress perfusion imaging using (99m)Tc single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD., Methods and Results: Chronic, stable, chest pain patients (n=662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha=0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66-71%, P

Aims: Both contrast enhanced (CE) two-dimensional echocardiography (2DE) and three-dimensional echocardiography (3DE) have been proposed as techniques to improve the accuracy of left ventricular (LV) volume measurements. We sought to examine the accuracy of non-contrast (NC) and CE-2DE and 3DE for calculation of LV volumes and ejection fraction (EF), relative to cardiac magnetic resonance imaging (MRI)., Methods and Results: We studied 50 patients (46 men, age 63 +/- 10 year) with past myocardial infarction who underwent echocardiographic assessment of LV volume and function. All patients sequentially underwent NC-2DE followed by NC-3DE. CE-2DE and CE-3DE were acquired during contrast infusion. Resting echocardiographic image quality was evaluated on the basis of NC-2DE. The mean LV end-diastolic volume (LVEDV) of the group by MRI was 207 +/- 79 mL and was underestimated by 2DE (125 +/- 54 mL, P = 0.005), and less by CE-2DE (172 +/- 58 mL, P = 0.02) or 3DE (177 +/- 64 mL, P = 0.08), but EDV was comparable by CE-3DE (196 +/- 69 mL, P = 0.16). Limits of agreement with MRI were similar for NC-3DE and CE-2DE, with the best results for CE-3D. Results were similar for calculation of LVESV. Patients were categorized into groups of EF (< or =35, 35-50, >50%) by MRI. NC-2DE demonstrated a 68% agreement (kappa 0.45, P = 0.001), CE-2DE a 62% agreement (kappa 0.20, P = 136), NC-3DE a 74% agreement (kappa 0.39, P = 0.005) and CE-3DE an 80% agreement (kappa 0.56, P < 0.001)., Conclusion: CE-2DE is analogous to NC-3DE in accurate categorization of LV function. However, CE-3DE is feasible and superior to other NC- and CE-techniques in patients with previous infarction.

Context: Obesity and insulin resistance (IR) may produce disturbances of left ventricular (LV) function. Obese women with polycystic ovary syndrome (PCO), characterized by hormonal and metabolic abnormalities, are thought to be at particularly increased cardiovascular risk., Objectives: We sought to determine the influence of IR on LV function in obese young women with and without PCO and without other comorbidities., Design: This was a cross-sectional study., Setting: The study was performed at a university hospital., Patients: A total of 150 women aged younger than 40 yr with a body mass index (BMI) of 30 kg/m(2) or more was classified into three groups: with both PCO and IR, without PCO and with IR, and without either PCO or IR., Main Outcome Measures: Tissue Doppler-derived myocardial velocities, strain-rate and strain, and metabolic and hormonal measurements were calculated., Results: Subclinical impairment of LV systolic and diastolic function as indicated by lower peak strain (P < 0.001), peak systolic strain rate (P < 0.001), peak early diastolic strain rate (P < 0.001), and peak early diastolic velocity (P < 0.01) was demonstrated in both groups with IR. IR subjects with and without PCO did not differ in any LV function indices. Strain was independently associated with fasting insulin (beta = -0.39; P < 0.001), urinary albumin excretion (UAE) (beta = -0.36; P < 0.001), and BMI (beta = -0.22; P < 0.03), and peak early diastolic strain rate was associated with UAE (beta = -0.35; P < 0.001), fasting insulin (beta = -0.24; P < 0.02), BMI (beta = -0.23; P < 0.02), and SHBG (beta = 0.20; P < 0.04)., Conclusions: In obese young women, fasting insulin, BMI, SHBG, and UAE are independent correlates of impaired LV performance. The contribution of PCO to LV function abnormalities is linked to IR, but not to other hormonal aberrations associated with this condition.

Aims: Transmural extent (TME) of myocardial scar, contractile reserve, and perfusion all predict improvement in regional myocardial function after coronary revascularization. We sought their association with regional remodelling after infarction., Methods and Results: We studied 89 patients (age 62 +/- 10 years) with left ventricular (LV) dysfunction, at least 1 month post infarction. Viability was identified by TME < 75% on contrast-enhanced magnetic resonance imaging (ce-MRI), augmentation at low-dose dobutamine echocardiography (DbE), or >60% uptake on delayed redistribution on TI-201 SPECT (single photon emission computed tomography). Coronary revascularization was performed in 36 patients. Regional LV end-diastolic volume (EDV) and end-systolic volume, and ejection fraction were measured with MRI at baseline and after a median follow-up of 18 months. Of 357 segments identified with subendocardial infarction (TME 0-25%) on ce-MRI, 176 were revascularized. Subendocardial scar segments were associated with reverse regional remodeling during follow-up. Revascularization was an independent correlate of change in EDV, but TME and revascularization showed no interaction with respect to their influence on regional volumes. Contractile reserve was present on DbE in 228 segments, of which 129 were TME 0-25%; remodelling was associated with intervention in non-transmural infarcts showing viability by DbE. Viability was identified by TI-201 SPECT in 381 segments (233 with TME 0-25%), but viability by SPECT was not associated with reverse remodelling. No significant reverse remodelling occurred in segments with intermediate scar thickness (TME 26-75%) or transmural scar, independent of revascularization or viability by DbE or TI-SPECT., Conclusion: Reverse regional remodelling is associated with subendocardial infarction, especially in the setting of contractile reserve and revascularization.

Background: A hypertensive response to exercise has prognostic significance. Patients with type 2 diabetes have vascular abnormalities which may predispose to exaggerated brachial and central blood pressure (BP) during exercise. This study aimed to test this hypothesis and to determine the clinical significance of high exercise BP by examining its relation to left ventricular (LV) mass., Methods: Brachial and central BP were recorded at rest and in response to maximal exercise in 73 diabetic patients (aged 54 +/- 10 years) and 73 controls (aged 53 +/- 12 years). Brachial BP was recorded using mercury sphygmomanometry and LV mass using 2D-echocardiography. Central BP was estimated by radial tonometry using an exercise-validated generalized transfer function., Results: At rest there were no significant (P > 0.05) differences between groups in brachial or central BP. The diabetic patients had significantly increased exercise brachial systolic BP (SBP: 199 +/- 25 mm Hg vs. 185 +/- 21 mm Hg; P = 0.002) and central SBP (158 +/- 17 mm Hg vs. 149 +/- 15 mm Hg; P = 0.002). There was a significantly higher prevalence of an exaggerated exercise BP response (> or =210/105 mm Hg; men and > or =190/105 mm Hg; women) in the diabetic patients (51% vs. 22%; P < 0.01). Compared with those with normal exercise BP, LV relative wall thickness (RWT) was significantly higher (0.41 +/- 0.09 vs. 0.36 +/- 0.08; P < 0.05) and LV hypertrophy was more prevalent (35% vs. 16%; P < 0.05) in those with a hypertensive response. After accounting for other confounding variables, exercise central SBP remained independently associated with LV RWT (beta = 0.22; P = 0.006)., Conclusion: Diabetic patients are more likely to exhibit exaggerated exercise BP. Regardless of disease status, high exercise central SBP may contribute to cardiovascular risk via adverse cardiac remodeling.

Background: Three-dimensional echocardiography (3DE) appears to show incremental benefit over two-dimensional echocardiography (2DE), but it's uptake has been slow. We tested attendees before and after an intensive interactive training course to identify its efficacy., Methods: Attendees (n = 35, 23 cardiologists, 12 sonographers) were shown how to use 3DE review software and asked to identify the pathology of five patients (wall motion abnormality, peri-prosthetic mitral regurgitation, subaortic membrane, small ventricular septal defect, submitral stenosis) on 2D and 3D images. In the following one and a half-day interactive teaching course, brief presentations on application of 3DE for assessment of wall motion, valve and congenital abnormalities were followed by review of 3D datasets, during which the attendees made their own interpretations before being shown the optimal viewing strategy. Test cases were not discussed and the test was repeated at the end of the course., Results: Most attendees (57%) had access but with little or no use of a 3DE system. Three-dimensional echocardiography had no incremental value before training. After training, overall correct responses significantly improved compared with baseline interpretation, although improvement was not the same for all diagnoses. All groups (cardiologists vs. sonographers, inexperienced vs. moderately experienced reviewers) improved similarly., Conclusions: Incorporation of 3DE into standard practice may be limited by inexperience. An interactive teaching course with rehearsal and direct mentoring appears to overcome this limitation and may improve the uptake of this technique.

Aims: Two-dimensional (2D)-strain derived from speckle-tracking is an alternative to tissue velocity imaging (TVI)-based strain. We compared their feasibility and accuracy in 150 patients undergoing dobutamine stress echocardiography (DSE) and coronary angiography., Methods and Results: 2D- and TVI-strain were obtained in three apical views at rest and peak stress. Peak systolic strain rate (SR), endsystolic strain (epsilon(end-sys)), and peak strain (epsilon(peak)) were measured off-line at rest and peak stress, and results were compared with wall motion analysis and significant coronary artery disease (CAD > or = 70% diameter stenosis). Optimal cut-offs were derived from receiver operating characteristic (ROC) curves for sentinel segments. The most feasible method was 2D-strain at rest, and TVI-strain at peak stress. The average peak SR and epsilon(end-sys) at peak stress in segments of patients with significant CAD was less than in segments of patients without CAD (P < 0.0001) and mean PSI at peak stress was higher (P < 0.0001) with both 2D- and TVI-strain. Peak systolic SR at peak stress had the best area under the ROC for both 2D- (AUC 0.67) and TVI-strain (AUC 0.71) for the diagnosis of CAD. The accuracy of WMS (75%) for diagnosis of CAD per patient was similar to 2D-SR (69%) and TVI-SR (74%). The accuracy of 2D-SR and TVI-SR at peak stress was 78 vs. 79% (P = NS) for LAD, 67 vs. 73% (P = NS) for LCX, and 59 vs. 74% (P = 0.008) for RCA disease., Conclusion: Measurement of speckle tracking strain during DSE is feasible and similar in accuracy to TVI-strain in the anterior, but not in the posterior circulation.

The management of asymptomatic severe mitral regurgitation is showing an increasing trend towards early surgery. However, in situations where either the valve or the patient is not optimal for surgery, watchful waiting remains a reasonable policy. In this situation, the longstanding challenge of assessing left ventricular function in the setting of severe mitral regurgitation has been simplified by a number of investigations, including stress echocardiography and myocardial imaging. This paper reviews the evidence base for each of these techniques.