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Background: Machine learning (ML) employs algorithms that learn from data, building models with the potential to predict events by aggregating a large number of variables and assessing their complex interactions. The aim of this study is to assess ML potential in identifying patients with ischemic heart disease (IHD) at high risk of cardiac death (CD)., Methods: 3987 (mean age 68 ± 11) hospitalized IHD patients were enrolled. We implemented and compared various ML models and their combination into ensembles. Model output constitutes a new ML indicator to be employed for stratification. Primary variable importance was assessed with ablation tests., Results: An ensemble classifier combining three ML models achieved the best performance to predict CD (AUROC of 0.830, F1-macro of 0.726). ML indicator use through Cox survival analysis outperformed the 18 variables individually, producing a better stratification compared to standard multivariate analysis (improvement of ∼20%). Patients in the low risk group defined through ML indicator had a significantly higher survival (88.8% versus 29.1%). The main variables identified were Dyslipidemia, LVEF, Previous CABG, Diabetes, Previous Myocardial Infarction, Smoke, Documented resting or exertional ischemia, with an AUROC of 0.791 and an F1-score of 0.674, lower than that of 18 variables. Both code and clinical data are freely available with this article., Conclusion: ML may allow a faster, low-cost and reliable evaluation of IHD patient prognosis by inclusion of more predictors and identification of those more significant, improving outcome prediction towards the development of precision medicine in this clinical field., Competing Interests: Declaration of competing interest there is no conflict of interest to declare by all authors., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF)., Methods: In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings., Results: We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70-84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80, p < 0.0001). Halving B-lines during hospitalization further improved event classification (continuous net reclassification improvement = 22.8%, p = 0.04)., Conclusions: The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes.

Background: Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear., Methods: Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples., Results: We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%., Conclusion: cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial., (Copyright © 2021. Published by Elsevier Inc.)

Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical conundrum accounting for about 6%-8% of all acute MI who are referred for coronary angiography. Current guidelines and consensus documents recommend that these patients are appropriately diagnosed, uncovering the causes of MINOCA, so that specific therapies can be prescribed. Indeed, there are a variety of causes that can result in this clinical condition, and for this reason diagnostic cardiac imaging has an emerging critical role in the assessment of patients with suspected or confirmed MINOCA. In last years, different cardiac imaging techniques have been evaluated in this context, and the comprehension of their strengths and limitations is of the utmost importance for their effective use in clinical practice. Moreover, recent evidence is clearly suggesting that a multimodality cardiac imaging approach, combining different techniques, seems to be crucial for a proper management of MINOCA. However, great variability still exists in clinical practice in the management of patients with suspected MINOCA, also depending on the availability of diagnostic tools and local expertise. Herein, we review the current knowledge supporting the use of different cardiac imaging techniques in patients with MINOCA, underscoring the importance of a comprehensive multimodality cardiac imaging approach and proposing a practical diagnostic algorithm to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Lung ultrasound B-lines are the sonographic sign of pulmonary congestion and can be used in the differential diagnosis of dyspnoea to rule in or rule out acute heart failure (AHF). Our aim was to assess the prognostic value of B-lines, integrated with echocardiography, in patients admitted to a cardiology department, independently of the initial clinical presentation, thus in patients with and without AHF, and in AHF with reduced and preserved ejection fraction (HFrEF and HFpEF)., Methods and Results: We enrolled consecutive patients admitted for various cardiac conditions. Patients were classified into three groups: (i) acute HFrEF; (ii) acute HFpEF; and (iii) non-AHF. All patients underwent an echocardiogram coupled with lung ultrasound at admission, according to standardized protocols. We followed up 1021 consecutive inpatients (69 ± 12 years) for a median of 14.4 months (interquartile range 4.6-24.3) for death and rehospitalization for AHF. During the follow-up, 126 events occurred. Admission B-lines > 30, ejection fraction < 50%, tricuspid regurgitation velocity > 2.8 m/s, and tricuspid annular plane systolic excursion < 17 mm were independent predictors at multivariable analysis. B-lines > 30 had a strong predictive value in HFpEF and non-AHF, but not in HFrEF., Conclusions: Ultrasound B-lines can detect subclinical pulmonary interstitial oedema in patients thought to be free of congestion and provide useful information not only for the diagnosis but also for the prognosis in different cardiac conditions. Their added prognostic value among standard echocardiographic parameters is more robust in patients with HFpEF compared with HFrEF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: To investigate the prognostic relevance of coronary anatomy, coronary function, and early revascularization in patients with stable coronary artery disease (CAD)., Methods and Results: From March 2009 to June 2012, 430 patients with suspected CAD (61 ± 9 years, 62% men) underwent coronary anatomical imaging by computed tomography coronary angiography (CTCA) and coronary functional imaging followed by invasive coronary angiography (ICA) if at least one non-invasive test was abnormal. Obstructive CAD was documented by ICA in 119 patients and 90 were revascularized within 90 days of enrolment. Core laboratory analysis showed that 134 patients had obstructive CAD by CTCA (>50% stenosis in major coronary vessels) and 79 significant ischaemia by functional imaging [>10% left ventricular (LV) myocardium]. Over mean follow-up of 4.4 years, major adverse events (AEs) (all-cause death, non-fatal myocardial infarction, or hospital admission for unstable angina or heart failure) or AEs plus late revascularization (LR) occurred in 40 (9.3%) and 58 (13.5%) patients, respectively. Obstructive CAD at CTCA was the only independent imaging predictor of AEs [hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.10-9.30; P = 0.033] and AEs plus LR (HR 4.3, 95% CI 1.56-11.81; P = 0.005). Patients with CAD in whom early revascularization was performed in the presence of ischaemia and deferred in its absence had fewer AEs, similar to patients without CAD (HR 2.0, 95% CI 0.71-5.51; P = 0.195)., Conclusion: Obstructive CAD imaged by CTCA is an independent predictor of clinical outcome. Early management of CAD targeted to the combined anatomical and functional disease phenotype improves clinical outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Introduction: Since inflammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifier of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients., Objective and Methods: We investigated the effect modification by systemic inflammation (serum CRP) on the relationship between a surrogate of the filling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantified by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model., Results: At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r = 0.23, P < 0.001) and serum CRP was a robust modifier of this relationship (P < 0.001). Similarly, in fully adjusted longitudinal analyses US-B lines associated with simultaneous estimates of LAVI (P = 0.002) and again CRP was a strong modifier of this relationship in adjusted analyses (P ≤ 0.01). Overall, at comparable LAVI levels, lung congestion was more pronounced in inflamed than in non-inflamed patients., Conclusion: In ESKD systemic inflammation is a modifier of the relationship between LAVI, an integrate measure of LV filling pressure, and lung water. For any given pressure, lung water is increased with higher CRP levels, likely reflecting a higher permeability of the alveolar-capillary barrier.

Background: Coronary allograft vasculopathy (CAV) is the main factor limiting long-term survival after cardiac transplantation. Dual imaging stress echocardiography with wall motion and Doppler-derived coronary flow reserve (CRF) of the left anterior descending artery (LAD) is a state-of-the-art methodology during dipyridamole stress echocardiography (DiSE). This study involving 74 heart transplanted patients has the purpose to assess the diagnostic value of dipyridamole stress echocardiography with evaluation of wall motion (WM) and Doppler-derived coronary flow reserve for the diagnosis of coronary allograft vasculopathy., Methods and Results: All patients underwent DiSE and coronary angiography. Moderate-severe CAV was defined according to International Society of Heart and Lung Transplant (ISHLT) recommended nomenclature for CAV, and CFR < 2 was considered to be impaired. Moderate-severe CAV was present in 11 patients. WM analysis revealed four patients (5%) with rest WM abnormalities. CFR analysis revealed that 40 (54%) individuals had an abnormal result. The combined evaluation of WM analysis and CFR resulted in a sensitivity of 72.7% (95% CI: 39.3 to 92.6%), a specificity of 49.2% (95% CI: 36.5 to 61.9%), a positive predictive value of 20% (95% CI: 9.6 to 36.1%), and negative predictive value of 91.1% (95% CI: 75.1 to 97.6%) for the diagnosis of CAV., Conclusions: Our results support the inclusion of DiSE performance in Heart transplant follow up protocol. The addition of CFR evaluation offers valuable information to the angiography findings in the detection of CAV and could be helpful in selected patients to adjust the time and indications of coronary angiography., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent technological advances in echocardiography, with progressive miniaturization of ultrasound machines, have led to the development of handheld ultrasound devices (HUD). These devices, no larger than some mobile phones, can be used to perform partial, focused exams as an extension to the physical examination. The European Association of Cardiovascular Imaging (EACVI) acknowledges that the dissemination of appropriate HUD use is inevitable and desirable, because of its potential impact on patient management. However, as a scientific society of cardiac imaging, our role is to provide guidance in order to optimize patient benefit and minimize drawbacks from inappropriate use of this technology. This document provides updated recommendations for the use of HUD, including nomenclature, appropriateness, indications, operators, clinical environments, data management and storage, educational needs, and training of potential users. It also addresses gaps in evidence, controversial issues, and future technological developments., (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: To assess the prognostic value of dual imaging stress echocardiography after coronary artery bypass grafting (CABG). Dual imaging stress echocardiography, combining the evaluation of regional wall motion and Doppler echocardiographic derived coronary flow velocity reserve (CFVR) of the left anterior descending artery (LAD), is the state-of-the-art methodology during vasodilatory stress., Methods and Results: In a prospective, multicenter, observational study, 349 patients (270 men; 69 ± 9 years; 262 symptomatic) with history of CABG underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFVR evaluation of LAD by Doppler. The composite endpoint of death and myocardial infarction was considered in the survival analysis. Positivity rate with either criteria was 13% in the 262 symptomatic patients with appropriate and 6% in the 87 asymptomatic patients with maybe/rarely appropriate indications on the basis of 2014 American College of Cardiology Foundation guidelines. During a median follow-up of 22 months (1st quartile 8, 3rd quartile 44), there were 56 (16%) events: 21 deaths, and 35 nonfatal myocardial infarctions. At Cox analysis, ischemia at stress echo (HR 4.80, 95% CI 2.69-8.55; p < 0.0001), and CFVR of LAD ≤2 (HR 2.28, 95% CI 1.32-3.95; p = 0.003) were multivariable prognostic predictors. Considering the group with no ischemia, patients with CFVR ≤2 showed 2.5 fold higher yearly hard events as compared to those with CFVR >2 (7.5 vs 2.9%; p = 0.002)., Conclusions: Dual imaging stress echocardiography provides useful prognostic information following CABG. Inducible ischemia and abnormal CFVR are strong and independent prognostic indicators in patients with appropriate and rarely/maybe appropriate indications., (Copyright © 2018. Published by Elsevier B.V.)

Background: Vasodilator stress echocardiography (SE) allows combined evaluation of regional wall motion and Doppler coronary flow velocity reserve (CFVR) of both the left anterior descending coronary artery (LAD) and the right coronary artery (RCA). The aim of this study was to prospectively assess the prognostic correlates of LAD and RCA CFVR on SE., Methods: A total of 1,365 patients with known or suspected coronary artery disease underwent dipyridamole SE with combined evaluation of CFVR in both the LAD and the RCA., Results: Ischemia was present on SE in 263 patients (19%). CFVR was abnormal (≤2.0) in 545 patients (40%): 172 in the LAD only, 149 in the RCA only, and 224 in both the LAD and the RCA. During a median follow-up period of 20 months, 44 deaths and 98 myocardial infarctions occurred. In the overall population, LAD CFVR ≤ 2.0 (hazard ratio [HR], 3.93) and inducible ischemia (HR, 2.74) were multivariate prognostic predictors. In the subset with ischemia on SE, CFVR did not add to peak wall motion score index (HR, 2.23). In patients without ischemia on SE, age (HR, 1.04), anti-ischemic therapy at the time of testing (HR, 1.6) and LAD CFVR ≤ 2.0 (HR, 10.8) were independent prognostic indicators. In patients without ischemia on SE and LAD CFVR >2.0, the 4-year event rate was 4% in those with RCA CFVR > 2.0 and 18% in those with RCA CFVR ≤ 2.0 (P < .0001)., Conclusions: Ischemia on SE with high peak wall motion score index identifies a high-risk subset regardless of the underlying CFVR response. Absence of ischemia on SE is associated with intermediate risk, and LAD CFVR is essential to identify a truly low-risk subset. RCA CFVR is less useful than LAD CFVR but may have a role for further risk stratification in patients without ischemia and normal LAD CFVR., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term)., Background: The epidemic of overweight involves pregnant women. The uterine environment affects organ development, modulating disease susceptibility. Offspring of obese mothers have higher rates of cardiovascular events and mortality., Methods: Echocardiography was performed in infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. In minipigs born to mothers fed a high-fat diet or a normal diet, cardiac development (echocardiography, histology), glucose metabolism and perfusion (positron emission tomography), triglyceride and glycogen content, and myocardial enzymes regulating metabolism (mass spectrometry) were determined from birth to adulthood., Results: In neonates, maternal overweight, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth (4.1 ± 0.3 vs. 3.3 ± 0.2 mm; p < 0.05) and larger end-diastolic and stroke volumes at 1 year. Minipigs born to mothers fed a high-fat diet showed greater left ventricular mass (p = 0.0001), chambers (+100%; p < 0.001), stroke volume (+75%; p = 0.001), cardiomyocyte nuclei (+28%; p = 0.02), glucose uptake, and glycogen accumulation at birth (+100%; p < 0.005), with lower levels of oxidative enzymes, compared with those born to mothers fed a normal diet. Subsequently, they developed myocardial insulin resistance and glycogen depletion. Late adulthood showed elevated heart rate (111 ± 5 vs. 84 ± 8 beats/min; p < 0.05) and ejection fraction and deficient fatty acid oxidative enzymes., Conclusions: Neonatal changes in cardiac morphology were explained by late-trimester maternal body mass index; myocardial glucose overexposure seen in minipigs can justify early human findings. Longer term effects in minipigs consisted of myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known., Methods: We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography., Results: Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects ( P = 0.001) and reversible wall motion abnormalities ( P = 0.008). Age ( P = 0.009), estimated glomerular filtration rate ( P = 0.01), LV mass ( P = 0.003), LVEF ( P = 0.03), and evidence of reversible myocardial ischemia ( P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L., Conclusions: hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD., (© 2018 American Association for Clinical Chemistry.)

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65-89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid-femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P =0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10 -3 ; P =0.009); only the latter remained significant after adjustment for confounders ( P =0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P =0.006; P =0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34 + cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa -1 ; P =0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34 + cells, and preserved carotid distensibility., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01725178., (© 2018 American Heart Association, Inc.)

Objectives: To assess the value of a simple score integrating non-ischaemia-related variables in expanding the wall motion abnormalities risk power during stress echocardiography (SE)., Methods: Study includes 14 279 patients who underwent SE for evaluation of coronary artery disease. All-cause death was the end point. Patients were randomly divided into the modelling and validation group of equal size. In the modelling group, multivariate analysis was conducted using clinical, rest and SE data, and a score was obtained from the number of non-ischaemia-related independent prognostic predictors. The score prognostic capability was compared in both groups., Results: During a median follow-up of 31 months, 1230 patients died: 622 (9%) in the modelling and 608 (9%) in the validation group (p=0.68). Independent predictors of mortality were ischaemia at SE (HR 1.77, 95% CI 1.49 to 2.12; p<0.0001) and six other parameters: age > 65 years, wall motion at rest, diabetes, left bundle branch block, anti-ischaemic therapy and male sex. Risk score resulted prognostically effective in the modelling and validation groups, both with and without inducible ischaemia subset. When risk score was included in the multivariate analysis, besides ischaemia at SE it was the only independent predictor of mortality in the modelling (HR 1.70, 95% CI 1.60 to 1.82; p<0.0001), in the validation (HR 1.77, 95% CI 1.65 to 1.90; p<0.0001) and in the overall group (HR 1.73, 95% CI 1.66 to 1.82; p<0.0001)., Conclusions: Simple clinical variables may be able to optimise SE risk stratification., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Stress echocardiography (SE) predicts cardiac death, but an increasing share of cardiac patients eventually die of cancer. The aim of the study was to assess whether SE positivity predicts cancer death., Methods and Results: In a retrospective analysis of prospectively acquired single-center, observational data, we evaluated 4673 consecutive patients who underwent SE from 1983 to 2009. All patients were cancer-free at index SE and were followed up for a median of 131 months (interquartile range 134). We separately analyzed predetermined end points: cardiovascular, cancer, and noncardiovascular, noncancer death, with and without competing risk. SE was positive in 1757 and negative in 2916 patients; 869 cardiovascular, 418 cancer, and 625 noncardiovascular, noncancer deaths were registered. The 25-year mortality was higher in SE-positive than in SE-negative patients, considering cardiovascular (40% versus 31%; P <0.001) and cancer mortality (26% versus 17%; P <0.01). SE positivity was a strong predictor of cancer (cause-specific hazard ratio 1.19; 95% confidence interval, 1.16-1.73; P =0.05) and cardiovascular mortality (1.18; 95% confidence interval, 1.03-1.35; P =0.02). Fine-Gray analysis to account for competing risk gave similar results. Cancer risk diverged after 15 years, whereas differences were already significant at 5 years for cardiovascular risk., Conclusions: SE results predict cardiovascular and cancer mortality. SE may act as a proxy of the shared risk factor milieu for cancer or cardiovascular death., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Pulmonary congestion is the main cause of hospital admission among heart failure (HF) patients. Lung ultrasound (LUS) assessment of B-lines has been recently proposed as a reliable and easy tool for evaluating pulmonary congestion., Objective: To determine the prognostic value of LUS in predicting adverse events in HF outpatients., Methods: Single-center prospective cohort of 97 moderate-to-severe systolic HF patients (53±13years; 61% males) consecutively enrolled between November 2011 and October 2012. LUS evaluation was performed during the regular outpatient visit to evaluate the presence of pulmonary congestion, determined by B-lines number. Patients were followed up for 4months to assess admission due to acute pulmonary edema., Results: During follow-up period (106±12days), 21 hospitalizations for acute pulmonary edema occurred. At Cox regression analysis, B-lines number≥30 (HR 8.62; 95%CI: 1.8-40.1; p=0.006) identified a group at high risk for acute pulmonary edema admission at 120days, and was the strongest predictor of events compared to other established clinical, laboratory and instrumental findings. No acute pulmonary edema occurred in patients without significant pulmonary congestion at LUS (number of B-lines<15)., Conclusion: In a HF outpatient setting, B-line assessment by LUS identifies patients more likely to be admitted for decompensated HF in the following 4months. This simple evaluation could allow prompt therapy optimization in those patients who, although asymptomatic, carry a significant degree of extravascular lung water., Condensed Abstract: Pulmonary congestion is the main cause of hospital admissions among heart failure patients. Lung ultrasound can be used as a reliable and easy way to evaluate pulmonary congestion through assessment of B-lines. In a cohort of heart failure outpatients, a B-lines cutoff≥30 (HR 8.62; 95%CI: 1.8-40.1) identified patients most likely to develop acute pulmonary edema at 120-days., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The aim of our study was to evaluate the relationship of pulse pressure (PP), a raw index of arterial stiffness, with noninvasively determined coronary flow reserve (CFR) and its components, in patients with angiographically normal epicardial coronary arteries., Methods and Results: The study population included 398 patients without angiographic evidence of coronary stenosis, who underwent high-dose dipyridamole stress echocardiography with transthoracic-derived CFR evaluation on the left anterior descending artery. CFR was calculated as the ratio between high-dose dipyridamole and resting coronary diastolic peak velocities. Patients were divided into 2 groups: the first group included the first and second PP tertiles (n=298, PP ≤60 mm Hg) and the second group included the highest PP tertile (n=100, PP >60 mm Hg). Mean blood pressure, systolic blood pressure (both P <0.0001), age ( P <0.002), and left ventricular mass index ( P =0.013) were higher in the highest PP tertile, which also showed higher resting coronary flow velocity (31.6±9.6 cm/s versus 27.7±6.4 cm/s, P <0.0001) and marginally lower CFR (2.5±0.6 versus 2.6±0.6, P =0.044). Hyperemic coronary flow velocity did not differ between the 2 groups. By separate multiple linear regression analyses, after adjusting for sex, age, the highest systolic blood pressure tertile (≥140 mm Hg), left ventricular mass index, and cardiovascular risk factors, the highest PP tertile was associated with resting coronary flow velocity ( P =0.003) and only marginally with hyperemic coronary flow velocity ( P <0.02), whereas its association with CFR was not significant., Conclusions: In patients without epicardial coronary artery stenosis, the highest PP tertile is associated with an increased coronary flow velocity at rest., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able to predict MCI with a good sensitivity and specificity (70.3 and 77.4% respectively). In MCI, olfactory identification score is correlated with a number of neurocognitive abilities, including overall cognitive status, dementia rating, immediate and delayed memory, visuospatial ability and verbal fluency. FMD was reduced in MCI (2.90 ± 2.15 vs. 3.66 ± 1.96%, P = 0.016) and was positively associated with olfactory identification score (ρ s =0.219, P = 0.025). The association remained significant after controlling for age, gender, and smoking. In conclusion, olfactory evaluation is able to discriminate between MCI and healthy individuals. Systemic vascular dysfunction might be involved, at least indirectly, in olfactory dysfunction in MCI., (© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)