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Purpose: Candidemia is a highly lethal infection; several scores have been developed to assist the diagnosis process and recently different models have been proposed. Aim of this work was to assess predictive performance of a Random Forest (RF) algorithm for early detection of candidemia in the internal medical wards (IMWs)., Methods: A set of 42 potential predictors was acquired in a sample of 295 patients (male: 142, age: 72 ± 15 years; candidemia: 157/295; bacteremia: 138/295). Using tenfold cross-validation, a RF algorithm was compared with a classic stepwise multivariable logistic regression model; discriminative performance was assessed by C-statistics, sensitivity and specificity, while calibration was evaluated by Hosmer-Lemeshow test., Results: The best tuned RF algorithm demonstrated excellent discrimination (C-statistics = 0.874 ± 0.003, sensitivity = 84.24% ± 0.67%, specificity = 91% ± 2.63%) and calibration (Hosmer-Lemeshow statistics = 12.779 ± 1.369, p = 0.120), markedly greater than the ones guaranteed by the classic stepwise logistic regression (C-statistics = 0.829 ± 0.011, sensitivity = 80.21% ± 1.67%, specificity = 84.81% ± 2.68%; Hosmer-Lemeshow statistics = 38.182 ± 15.983, p < 0.001). In addition, RF suggests a major role of in-hospital antibiotic treatment with microbioma highly impacting antimicrobials (MHIA) that are found as a fundamental risk of candidemia, further enhanced by TPN. When in-hospital MHIA therapy is not performed, PICC is the dominant risk factor for candidemia, again enhanced by TPN. When PICC is not used and MHIA therapy is not performed, the risk of candidemia is minimum, slightly increased by in-hospital antibiotic therapy., Conclusion: RF accurately estimates the risk of candidemia in patients admitted to IMWs. Machine learning technique might help to identify patients at high risk of candidemia, reduce the delay in empirical treatment and improve appropriateness in antifungal prescription.

Aims: Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2))., Methods: In an individual patient dataset, BMI was calculated as weight (kg)/height (m) 2 , and PBF through the Jackson-Pollock and Gallagher equations., Results: Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5-2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4-33.0%) with the Jackson-Pollock equation, and 28.0% (23.8-33.5%) with the Gallagher equation, with an extremely strong correlation ( r  = 0.996, p  < 0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI ≥ 30 kg/m 2 , third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome., Conclusion: In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients.

Background: The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study., Methods: Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18-65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays., Results: On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap)., Conclusions: Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method., Materials and Methods: Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease., Results and Conclusions: The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Cluster of microcalcifications can be an early sign of breast cancer. In this paper, we propose a novel approach based on convolutional neural networks for the detection and segmentation of microcalcification clusters. In this work, we used 283 mammograms to train and validate our model, obtaining an accuracy of 99.99% on microcalcification detection and a false positive rate of 0.005%. Our results show how deep learning could be an effective tool to effectively support radiologists during mammograms examination.

Pertussis is quite frequent and severe among infants; therefore, rapid diagnosis and timely targeted therapy are essential. Although a molecular test for etiological diagnosis is now available, it may not be available everywhere, and therefore adjunctive diagnostic tests are still useful for presumptive diagnosis. We describe the use of procalcitonin (PCT) and lymphocyte count to discriminate among pertussis, bacterial and viral infections. Fourteen infants per group were studied. The decision tree, built considering all available variables, showed a major role of PCT in predicting the different groups. A PCT value equal to or greater than 0.75 ng/ml selected for bacterial infections. A PCT value lower than 0.75 ng/ml and a lymphocyte count equal to or greater than 10,400/mm3 selected the subjects with pertussis, while a lymphocyte count lower than 10,400/mm3 selected for viral etiology. PCT should be used in the diagnosis of infants suspected of having pertussis.

Candida is an increasing cause of bloodstream infection and is associated with significant morbidity and mortality. The aim of our study is to analyze risk factors for short-term mortality in patients with bloodstream Candida spp. infections admitted to Internal Medicine Wards (IMWs). This was a retrospective case-control study between January 2012 and December 2014 from four University Hospitals in Italy, where patients with candidemia dying within 30 days from diagnosis were matched to control cases with candidemia who survived in the same period of time. Two-hundred and fifty cases of candidemia were registered during the 36 months of enrollment. Among these, 112 patients died (45%) within 30 days from the first blood culture's positivity for Candida spp. At multivariate analysis, septic shock [odds ratio (95% CI) = 2.919 (1.62-5.35), p < 0.001] and concomitant chronic kidney failure [odds ratio (95% CI) = 2.296 (1.07-5.12), p = 0.036] were independent predictors of mortality. Low-dose chronic steroid therapy was protective [odds ratio (95% CI) = 0.461 (0.25-0.83), p = 0.011).

Serum angiopoietin-2 level is elevated in several diseases suggesting its possible role as a mediator of angiogenesis and vascular network remodeling. Triiodothyronine and thyroxine have well documented effects on angiogenesis in vitro, but only few reports have studied angiopoietin-2 in thyroid-disease patients. The aim of the present study was to measure soluble angiopoietin-2 serum levels in a group of thyroid-disease patients with different levels of free triiodothyronine and thyroxine. Angiopoietin- 2 were quantified by ELISA in sera of fifteen healthy volunteers and forty-two thyroid ambulatory patients: nine with hyperthyroidism, four in therapy for hyperthyroidism, seven with subclinal hyperthyroidism, twelve with hypothyroidism, five with thyroiditis and five in therapy for thyroiditis. Median angiopoietin-2 level was significantly elevated in hyperthyroid patients (p < 0.01) and it was significantly increased vs all the other groups (p < 0.0001). In hyperthyroid patients anti thyroid therapy seems to reduce angiopoietin-2 level. A significant positive correlation was observed between Log angiopoietin-2 levels and serum concentration of Log free triiodothyronine (r = 0.4, P < 0.001) and Log free thyroxine (r = 0.4, P < 0.001) respectively. In conclusion, increased levels of angiopoietin-2 are present in hyperthyroid patients, and seems to correlate with free triiodothyronine and free thyroxine levels but not with anti-thyroid antibodies. These findings suggest angiopoietin-2 as a mediator of angiogenesis and vascular network remodeling in this disease, but further studies will be needed to determine the role of this biomarker in the pathophysiology and progression of hyperthyroidism., (Copyright: © 2016 by Fabrizio Serra editore, Pisa · Roma.)

Background: Systematic difference between thyroid-stimulating hormone (TSH) immunoassays may produce misleading interpretation when samples of the same patients are measured with different methods. The study aims were to evaluate whether systematic differences are present among TSH immunoassays, and whether it is possible to obtain a better harmonization among TSH methods using results obtained in external quality assessment (EQA) schemes., Methods: Seven Italian clinical laboratories measured TSH in 745 serum samples of healthy subjects and patients with thyroid disorders. These samples were also re-measured by two reference laboratories of the study with the six TSH immunoassays most popular in Italy after 2 months of storage at -80 °C. Moreover, these data were compared to 53,823 TSH measurements, obtained by laboratories participant to 2012-2015 EQA annual cycles in 72 quality control samples (TSH concentrations from about 0.1 mIU/L to 18.0 mIU/L). TSH concentrations were recalibrated using a mathematical approach based on the principal component analysis (PCA)., Results: Systematic differences were found between the most popular commercially available TSH immunoassays. TSH concentrations measured by the clinical laboratories were very closely correlated to those measured with the same method by reference laboratories after 2 months of storage at -80 °C. After recalibration using the PCA approach the variation of TSH values significantly decreased from a median pre-calibration value of 13.53% (10.79%-16.53%) to 9.63% (6.90%-13.21%) after recalibration., Conclusions: Our data suggest that EQA schemes are useful to improve harmonization among TSH immunoassays and also to produce some mathematical formulas, which can be used by clinicians to better compare TSH values measured with different methods.

Objectives: The purpose of this study was to perform the first meta-analysis of currently available data., Background: Soluble suppression of tumorigenesis 2 (sST2) plasma concentration is elevated in chronic heart failure (CHF) and helps to predict prognosis in this setting, although the evidence is limited., Methods: Three databases (Medline, Cochrane Library, and Scopus) were searched. Inclusion criteria were: follow-up studies; papers published in English; enrollment of CHF outpatients; available data on hazard ratio (HR) for the log 2 ST2 (so that the reported HRs represent the risk per doubling of sST2) and 95% confidence interval (CI) for all-cause death, and possibly also for cardiovascular (CV) death; and use of standardized sST2 assay. Exclusion criteria were: sST2 considered only as an element of a prognostic score, and studies on patients with end-stage HF., Results: Seven studies were finally included for all-cause death, with a global population of 6,372 patients; data on CV death were available for 5 studies, totaling 5,051 patients. The HR was 1.75 (95% CI: 1.37 to 2.22) for all-cause death and 1.79 (95% CI: 1.22 to 2.63) for CV death (both p < 0.001). Significant heterogeneity among studies was detected in the quantification of sST2 predictive value, attributable to marked differences in pharmacological treatment among trials. The predictive power of sST2 was greater when patients were managed according to present guideline-recommended medical treatment., Conclusions: sST2 is a predictor of both all-cause and CV death in CHF outpatients. The present meta-analysis supports the use of sST2 for risk stratification in patients with stable CHF., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to perform a meta-analysis of currently available data regarding the prognostic significance of soluble suppression of tumorigenecity-2 (sST2) concentration in acute heart failure (AHF)., Background: Concentration of sST2 may have prognostic value in AHF. A comprehensive assessment of all available studies regarding sST2 in AHF is lacking., Methods: Three databases (MEDLINE, Cochrane Library, and Scopus) were searched. Inclusion criteria were follow-up studies, papers published in English, enrollment of patients with AHF, and availability of median hazard ratios for all-cause death and other outcome measures, when available., Results: Ten studies were included, with a global population of 4,835 patients and a median follow-up duration of 13.5 months. The following global hazard ratios calculated for log 2 (sST2) were admission sST2 and all-cause death, 2.46 (95% confidence interval [CI]: 1.80 to 3.37; p < 0.001); discharge sST2 and all-cause death, 2.06 (95% CI: 1.37 to 3.11; p < 0.001); admission sST2 and cardiovascular death, 2.29 (95% CI: 1.41 to 3.73; p < 0.001); discharge sST2 and cardiovascular death, 2.20 (95% CI: 1.48 to 3.25; p < 0.001); admission sST2 and heart failure (HF) hospitalization, 1.21 (95% CI: 0.96 to 1.52; p = 0.060); discharge sST2 and HF hospitalization, 1.54 (95% CI: 1.03 to 2.32; p = 0.007); admission sST2 and all-cause death or HF hospitalization, 1.74 (95% CI: 1.24 to 2.45; p < 0.001); and discharge sST2 and all-cause death or HF hospitalization, 1.63 (95% CI: 1.14 to 2.33; p < 0.001)., Conclusions: Plasma sST2 has prognostic value with respect to all-cause and cardiovascular death as well as the composite outcome of all-cause death or HF hospitalization, with both admission and discharge values having prognostic efficacy. Discharge sST2, but not admission sST2, is predictive of HF rehospitalization during follow-up., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to identify the risk factors for ventilator associated pneumonia (VAP) due to Klebsiella pneumoniae carbapenemase-producing K (KPC-Kp) development in ICU patients with documented rectal and tracheal colonization., Methods: We performed a retrospective, matched case-control study in a medical-surgical ICU (January 2011-December 2013) comparing 30 patients who developed KPC-Kp VAP during the ICU stay to 60 colonized patients not developing KPC-Kp VAP. Analysed risk factors included: age, sex, SAPS II and SOFA scores, comorbidities, type and length of antibiotic therapy, previous non KPC-Kp infections, time between admission to rectal and tracheal colonization., Results: Several risk factors were more frequent among patients who developed KPC-Kp pneumonia versus matched colonized controls: previous infection not related to KPC-Kp (P<0.001), duration of previous antibiotic therapy before (P<0.001) and after (P=0.002) KPC-Kp colonization. Amoxicillin/clavulanic acid prophylaxis was administered in 17% of VAP patients versus 73% of patients not developing VAP (P<0.001). Multivariate conditional logistic regression analysis identified several significant independent risk factors favoring KPC-Kp VAP in patients colonized at multiple sites: previous non KPC-Kp infections (OR: 2.046), duration of previous antibiotic therapy before (OR: 1.309) and after (OR: 1.122) KPC-Kp colonization; antibiotic therapy with amoxicillin/clavulanic acid prophylaxis (<48 hours) was associated with reduced risk of KPC-Kp VAP (OR: 0.987)., Conclusions: In rectal and tracheal KPC-Kp colonized patients, prolonged antibiotic therapy administered for non KPC-Kp infection predisposes patients to subsequent KPC-Kp VAP. Short prophylaxis of early pneumonia with amoxicillin/clavulanic acid, reducing the need for subsequent antibiotic use, may be associated with reduced risk for KPC-Kp VAP.

The lack of interchangeable laboratory results and consensus in current practices has underpinned greater attention to standardization and harmonization projects. In the area of method standardization and harmonization, there is considerable debate about how best to achieve comparability of measurement for immunoassays, and in particular heterogeneous proteins. The term standardization should be used only when comparable results among measurement procedures are based on calibration traceability to the International System of Units (SI unit) using a reference measurement procedure (RMP). Recently, it has been promoted the harmonization of methods for many immunoassays, and in particular for thyreotropin (TSH), as accepted RMPs are not available. In a recent paper published in this journal, a group of well-recognized authors used a complex statistical approach in order to reduce variability between the results observed with the 14 TSH immunoassay methods tested in their study. Here we provide data demonstrating that data from an external quality assessment (EQA) study allow similar results to those obtained using the reported statistical approach.

There is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. Specifically, results from published experimental studies indicate that forces, when carefully controlled, can modulate neuronal regeneration. Here, we validate a non-invasive approach for physical guidance of nerve regeneration based on the synergic use of magnetic nanoparticles (MNPs) and magnetic fields (Ms). The concept is that the application of a tensile force to a neuronal cell can stimulate neurite initiation or axon elongation in the desired direction, the MNPs being used to generate this tensile force under the effect of a static external magnetic field providing the required directional orientation. In a neuron-like cell line, we have confirmed that MNPs direct the neurite outgrowth preferentially along the direction imposed by an external magnetic field, by inducing a net angle displacement (about 30°) of neurite direction. From the clinical editor: This study validates that non-invasive approaches for physical guidance of nerve regeneration based on the synergic use of magnetic nanoparticles and magnetic fields are possible. The hypothesis was confirmed by observing preferential neurite outgrowth in a cell culture system along the direction imposed by an external magnetic field., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Changes in cardiac gene expression due to myocardial injury are usually assessed in whole heart tissue. However, as the heart is a heterogeneous system, spatial and temporal heterogeneity is expected in gene expression., Results: In an ischemia/reperfusion (I/R) rat model we evaluated gene expression of mitochondrial and cytoplasmatic superoxide dismutase (MnSod, Cu-ZnSod) and thioredoxin reductase (trxr1) upon short (4 h) and long (72 h) reperfusion times in the right ventricle (RV), and in the ischemic/reperfused (IRR) and the remote region (RR) of the left ventricle. Gene expression was assessed by Real-time reverse-transcription quantitative PCR (RT-qPCR). In order to select most stable reference genes suitable for normalization purposes, in each myocardial region we tested nine putative reference genes by geNorm analysis. The genes investigated were: Actin beta (actb), Glyceraldehyde-3-P-dehydrogenase (gapdh), Ribosomal protein L13A (rpl13a), Tyrosine 3-monooxygenase (ywhaz), Beta-glucuronidase (gusb), Hypoxanthine guanine Phosphoribosyltransferase 1 (hprt), TATA binding box protein (tbp), Hydroxymethylbilane synthase (hmbs), Polyadenylate-binding protein 1 (papbn1). According to our findings, most stable reference genes in the RV and RR were hmbs/hprt and hmbs/tbp/hprt respectively. In the IRR, six reference genes were recommended for normalization purposes; however, in view of experimental feasibility limitations, target gene expression could be normalized against the three most stable reference genes (ywhaz/pabp/hmbs) without loss of sensitivity. In all cases MnSod and Cu-ZnSod expression decreased upon long reperfusion, the former in all myocardial regions and the latter in IRR alone. trxr1 expression did not vary., Conclusions: This study provides a validation of reference genes in the RV and in the anterior and posterior wall of the LV of cardiac ischemia/reperfusion model and shows that gene expression should be assessed separately in each region.

Background: Serum gamma-glutamyltransferase activity (GGT), even when within its normal reference range, catalyzes low density lipoprotein oxidation in vitro and predicts cardiovascular events. Of the four GGT fractions (b-GGT, m-GGT, s-GGT, and f-GGT) recently identified in blood, only b-GGT is found within atherosclerotic plaques. Our goal was to identify the determinants of the GGT fractions (b-, m-, s-, and f-GGT) and their association with established cardiovascular risk factors in healthy subjects., Methods: Multiple linear regression analysis was applied to estimate the association of fractional GGT with gender, age, body mass index, arterial pressure (AP), plasma glucose, alanine aminotransferase (ALT), high and low density lipoproteins (LDL-C) cholesterol (HDL-C), triglycerides (TG) and C-reactive protein (CRP) in 200 healthy subjects., Results: All GGT fractions were associated with ALT; b-GGT with AP, TG, and CRP; m-GGT with LDL-C, TG and CRP; s-GGT with TG and CRP, and f-GGT only with LDL-C, whereas gender was associated with s-GGT and f-GGT only., Conclusions: In healthy individuals, cardiovascular risk factors are associated with high molecular weight GGT fractions, namely with b-GGT, the only form present within the plaque. This finding adds to the present knowledge concerning the relevance of GGT, within its reference range, for atherosclerosis-related events.

The measurement of circulating brain natriuretic peptide (BNP) and its related peptide, the N-terminal fragment of proBNP (NT-proBNP), have a high degree of diagnostic accuracy and clinical relevance both in acute and chronic heart failure (HF). However, the role of measurement of BNP/NT-proBNP in the follow-up of treated HF patients is still debated. In this chapter, authors have studied the clinical impact of B-type natriuretic peptide assay in the follow-up of patients with heart failure, and, in particular, the possible role of the measurement of its circulating levels in guiding the treatment. A relatively small number of randomized studies were designed to specifically evaluate the clinical use of BNP/NT-proBNP assay in monitoring and tailoring the medical therapy in HF patients. A meta-analysis of results reported in these studies indicate that the inefficacy to improve the mortality rate of the peptide-guided compared to the control group found in some studies, may depend on to the inability of current therapeutic strategies to modify prognosis, especially in the elderly subset of patients, who are characterized by more advanced disease and comorbidities. Further prospective and randomized clinical studies are necessary to definitively demonstrate whether BNP/ NT-proBNP-guided therapy is able to significantly improve the outcome of patients with HF.

Background: Estimation of contractility of the left ventricle is an important, and as yet elusive, goal with noninvasive techniques., Objective: We sought to assess the feasibility of a totally noninvasive estimation of force-frequency relation (FFR) during exercise stress in the echocardiography laboratory., Methods: We enrolled 13 healthy control patients (12 men, age 38 +/- 15 years) as group I, and 50 patients (38 men, age 64 +/- 11 years) referred for exercise echocardiography as group II. To build the FFR, the force was determined at each step as the ratio of the systolic pressure (cuff sphygmomanometer)/end-systolic volume index (biplane Simpson's rule/body surface area). The slope of the relationship was calculated with the linear best fit of the FFR., Results: Noninvasive systolic pressure/end-systolic volume ratio was obtained in all patients. The slope of the linear best fit of the force-frequency curve was lower in group II compared with group I (group II = 10.1 +/- 9.3 x 10(-2) vs group I = 14.9 +/- 9.9 x 10(-2) group I, P =.04). By regional wall-motion analysis, 2 subgroups were identified in group II: group IIA (n = 8) had a positive echocardiogram; and group IIB (n = 42) had a negative echocardiogram. The slope of the force-frequency curve was lower in patients with ischemia compared with those without (group IIA = 3.5 +/- 4.2 x 10(-2) vs group IIB = 11.4 +/- 9.5 x 10(-2); P =.012). Heart rate-systolic pressure/end-systolic volume index relation was biphasic, with an initial positive slope and a subsequent negative slope in 1 patient of group I, 4 patients of group IIA, and 15 patients of group IIB (P <.05 vs group I)., Conclusion: A noninvasive estimation of FFR can be easily determined during exercise echocardiography. This index of global contractility is theoretically appealing for identification of limited contractile reserve and latent global left ventricular dysfunction.