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Background: The outcome of secondary mitral regurgitation (MR) in patients with heart failure is poor. Survival is related to the severity of MR. We sought to investigate the effect of left ventricular contractility, the ratio of left ventricular end-diastolic volume (LVEDV) to effective orifice area (EROA) and the ratio of regurgitant volume (RVol) to stroke volume (SV) on cardiovascular survival., Methods: 188 patients with a left ventricular ejection fraction (LVEF) < 50% and secondary MR were included. Groups were divided into tertiles. The Kaplan Meier method and log rank test were used to identify differences in survival between groups. Cox regression was used to identify independent predictors of cardiac mortality., Results: Median follow-up was 30.4 months. Patients with a more abnormal global longitudinal strain (GLS) had lower survival, p = 0.001. There was no difference in survival between patients with an LVEF <30%, 30%-40% and >40%, p = 0.27. Patients with a higher RVol/SV ratio had lower survival than those with a lower ratio, p < 0.0001. Patients with a lower LVEDV/EROA ratio had worse survival than those with a higher ratio, p < 0.0001. Independent predictors of cardiovascular mortality were GLS (<5.6%) hazard ratio (HR) 2.7, the ratio of RVol/SV (>1.38) HR 4.96 and the ratio of LVDEV to EROA (<263) HR 4.49., Conclusion: The main determinants of cardiovascular mortality in patients with secondary MR and heart failure are more abnormal GLS, lower LVEDV/EROA ratio and higher RVol/SV ratio. These may help risk stratify patients to help determine the optimal management strategy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Introduction: Exercise ECG (Ex-ECG) is advocated by guidelines for patients with low - intermediate probability of coronary artery disease (CAD). However, there are no randomized studies comparing Ex-ECG with exercise stress echocardiography (ESE) evaluating long term cost-effectiveness of each management strategy., Methods: Accordingly, 385 patients with no prior CAD and low-intermediate probability of CAD (mean pre-test probability 34%), were randomized to undergo either Ex-ECG (194 patients) or ESE (191 patients). The primary endpoint was clinical effectiveness defined as the positive predictive value (PPV) for the detection of CAD of each test. Cost-effectiveness was derived using the cumulative costs incurred by each diagnostic strategy during a mean of follow up of 3.0 years., Results: The PPV of ESE and Ex-ECG were 100% and 64% (p = 0.04) respectively for the detection of CAD. There were fewer clinic (31 vs 59, p < 0.01) and emergency visits (14 vs 30, p = 0.01) and lower number of hospital bed days (8 vs 29, p < 0.01) in the ESE arm, with fewer patients undergoing coronary angiography (13.4% vs 6.3%, p = 0.02). The overall cumulative mean costs per patient were £796 for Ex-ECG and £631 for ESE respectively (p = 0.04) equating to a >20% reduction in cost with an ESE strategy with no difference in the combined end-point of death, myocardial infarction, unplanned revascularization and hospitalization for chest pain between ESE and Ex-ECG (3.2% vs 3.7%, p = 0.38)., Conclusion: In patients with low to intermediate pretest probability of CAD and suspected angina, an ESE management strategy is cost-effective when compared with Ex-ECG during long term follow up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Patients with symptomatic left bundle branch block (LBBB) may have myocardial ischaemia due to both coronary artery disease and/or cardiomyopathy (microcirculatory abnormalities) and may have concomitant left ventricular (LV) dysfunction. We aimed to assess the feasibility and prognostic value of contemporary stress echocardiography (SE), which can uncover both pathophysiologies in LBBB patients in routine clinical practice, and also aimed to assess the additive value of contrast SE., Methods and Results: Accordingly, 190 consecutive patients (age 70.5 ± 11.3 years, LV ejection fraction = 50.1 ± 10%) with symptomatic LBBB who underwent SE over 6 years were assessed, of which 142 (75%) underwent contrast SE and 176 (92.6%) had diagnostic SE. Inducible ischaemia was present in 25 (14.2%) patients. During follow-up (35.4 ± 20.2 months) there were 32 deaths (18%) and 18 (10.2%) first cardiovascular (CV) events (acute myocardial infarction/mortality) in the 176 patients with diagnostic studies. Wall thickening score index at peak stress (WTSIpeak), which measures combined LV function and inducible ischaemia, was an independent predictor of mortality (HR = 3.78, 95% CI = 1.39-10.31, P = 0.01) and CV events (HR = 3.96, 95% CI = 1.1-14.3, P = 0.036). An abnormal SE (myocardial ischaemia and/or abnormal LV function) predicted an almost three-fold increase in all-cause mortality and CV events compared with normal SE. Amongst the confounders affecting assessment of wall thickening in LBBB and conventional prognostic variables, use of contrast was an independent predictor (P = 0.034) of WTSI1.16 (optimal predictor of mortality/CV outcome)., Conclusion: SE in patients with LBBB demonstrated high feasibility and the combination of LV systolic function and myocardial ischaemia provided important prognostic information. Contrast-enhanced SE improved the prediction of outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

Introduction: Although stress echocardiography (SE) is invaluable in younger populations, its prognostic value may be attenuated in the elderly due to shorter life expectancy and the frequent presence of severe comorbidities. This study sought to evaluate the clinical effectiveness of SE in octogenarians, particularly its prognostic value over clinical variables, in predicting hard events., Methods: A total of 374 consecutive octogenarians who underwent SE for evaluation of coronary artery disease (CAD) were assessed for feasibility, diagnostic accuracy and safety of the test, and followed up for hard outcomes (all-cause mortality, cardiovascular (CV) deaths and non-fatal myocardial infarction (NFMI)). Cox regression analysis was performed to identify predictors of outcome., Results: Of the 374 tests, 360 (96.3%) were diagnostic. Of the 50 patients with inducible ischaemia, 33 patients (66%) proceeded to angiography of which 27 (82%) patients had significant CAD. During long-term follow-up of 4.0±2.0 years, there were 127 deaths and 36 NFMIs. The annualised mortality, NFMI and combined mortality /NFMI rates were 8.1%, 1.8% and 9.4% for patients with a normal SE and 12.1%, 5.5% and 14.1% for those with an abnormal SE, respectively. Predictors of NFMI on multivariate analysis were prior CAD (HR 2.89, CI 1.03 to 8.15, p=0.045), peripheral vascular disease (HR 3.33, CI 1.18 to 9.45, p=0.02), and inducible ischaemia (HR 3.97, CI 1.49 to 10.55, p=0.006). In patients without prior history of CAD, inducible ischaemia was the only independent predictor of NFMI (HR 8.72, CI 1.46 to 52.2, p=0.018). The larger the extent of ischaemia, the greater the incidence of NFMI. The independent predictors of CV events (NFMI or CV mortality) were PAD (HR 2.81, CI 1.21 to 6.52, p=0.016) and peak wall motion score index (HR 5.71, CI 1.67 to 19.6, p=0.006). Although inducible ischaemia predicted all-cause mortality on unadjusted analysis, it did not on multivariate analysis., Conclusions: In octogenarians, SE demonstrated excellent feasibility, safety and diagnostic accuracy. SE parameters were independent predictors of NFMI and CV events, and the presence of inducible ischaemia was associated with a 50% increase in all-cause mortality., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose of Review: Left ventricular ejection fraction (LVEF) is a powerful prognostic marker in heart failure and plays a pivotal role in the allocation of many treatments that reduce morbidity and mortality. Although unenhanced two-dimensional echocardiography (2DE) is the most ubiquitous tool for the assessment of left ventricular (LV) size and systolic function, it does not provide reliable, reproducible and accurate measures. The purpose of this review is to critically appraise contrast echocardiography and three-dimensional echocardiography (3DE) for the assessment of LVEF and LV volumes., Recent Findings: Contrast echocardiography results in more accurate assessment of LVEF and LV volumes than unenhanced 2DE, significantly improving correlation with cardiac magnetic resonance, with comparable reproducibility. Contrast echocardiography reduces downstream testing, frequently alters patient management, and results in substantial cost savings. 3DE shows higher levels of agreement with cardiac magnetic resonance over unenhanced 2DE for LVEF and LV volumes, but requires adequate image quality, and consistently underestimates LV volumes due to limited spatial resolution., Summary: The advent of contrast 2DE and 3DE has marked the dawn of significant improvements in the precision and reproducibility of echocardiography. Contrast 3DE improves LV assessment in patients with suboptimal images, but further work is needed to demonstrate incremental benefit over contrast echocardiography.

Objective: Non-invasive cardiac imaging may suffer from poor image quality in morbidly obese individuals. This study aimed to determine the clinical value of contemporary stress echocardiography (SE) in morbidly obese patients referred for assessment of suspected coronary artery disease (CAD)., Methods: This prospective, multicentre observational study was conducted in two district hospitals and one tertiary centre in London, UK. Individuals with body mass index ≥35 kg/m(2) referred for SE were evaluated. The percentage of patients with obstructive CAD on coronary angiography, following abnormal SE, was assessed. Patient outcomes were determined with follow-up for the composite end-point of all-cause mortality, myocardial infarction and late revascularisation., Results: Over a 13-month period, 209 morbidly obese patients underwent SE, and contrast agent was used in 96% of patients. A diagnostic result was obtained in 200/209 (96%) patients. Of 32 (15%) patients with inducible ischaemia, 25 underwent angiography, 22 (88%) had corresponding significant CAD and, of these, 16 (77%) underwent revascularisation. Conversely, only 2/157 patients (1.3%) with normal SE underwent angiography, and none underwent revascularisation. Over a mean follow-up period of 17.8±5.4 months, there were nine events. The annualised cardiac event rate after a normal SE was 0.95%. Events were more frequent in patients with inducible ischaemia versus those without ischaemia (5/32 (15.6%) vs 4/153 (2.6%); p=0.002). Ejection fraction <50% (HR 9.5; 95% CI 2.4 to 38.0; p=0.002) and inducible ischaemia (HR 9.4; 95% CI 2.5 to 35.8; p=0.001) were predictors of outcome on univariable Cox regression analysis., Conclusions: Contemporary SE has excellent feasibility and positive predictive value and resulted in appropriate risk stratification of symptomatic patients with significant obesity. A normal SE portends an excellent outcome over the short-intermediate term in this high-risk patient population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Clopidogrel-naive patients subjected to coronary angiography may be candidates for percutaneous coronary intervention (PCI). Clopidogrel loading with 600 mg at least 2 hours before the procedure is advised for such patients. However, there is no direct evidence that delaying PCI for 2 hours after clopidogrel loading is superior to ad hoc PCI., Methods: After coronary angiography, clopidogrel-naive patients (N = 199) with stable or unstable angina, candidates for PCI, were loaded with 900 mg of clopidogrel and then randomized to ad hoc PCI (ad hoc group, n = 103) or delayed PCI 2 hours after loading (delayed group, n = 96). Combined primary end point was death/periprocedural myocardial infarction (MI)/stroke/reintervention within 30 days post-PCI. Secondary end points were periprocedural MI; periprocedural creatine kinase-MB elevation >3 x upper limit of normal; any periprocedural increase of creatine kinase-MB, troponin-I, or myoglobin above upper limit of normal; Thrombolysis in Myocardial Infarction flow <3 after PCI; thrombocytopenia with platelet count of <70,000/mL; major bleeding defined according to the Thrombolysis in Myocardial Infarction criteria; and elevation of high-sensitivity C-reactive protein and soluble P selectin., Results: Primary end point occurred in 12.6% ad hoc group versus 15.6% delayed group patients (P = .34). High-sensitivity C-reactive protein increased in both groups post-PCI (analysis of variance P < .0001) without difference between groups (P = .5). Major bleeding occurred in 2.9% ad hoc group versus 3.1% delayed group patients (P = .9). No significant difference was observed in any other secondary end point., Conclusions: In clopidogrel-naive patients, a strategy of delaying PCI for 2 hours after high-dose clopidogrel loading does not seem to confer any benefit compared to ad hoc PCI.