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Aims: Exercise stress echocardiography (ESE) is recommended by the European Society of Cardiology guidelines for the evaluation of heart failure (HF) patients. Recently, lung ultrasound (LUS) has been proposed for the assessment of extravascular lung water through B-lines. The aim of this study was to assess B-lines during ESE in HF.Methods and Results: Standard transthoracic and LUS evaluation was performed during semi-supine ESE in 103 NYHA class I-III HF patients (76 male; mean age 64 ± 12 years) with depressed left ventricular ejection fraction (35 ± 8%). B-lines were measured by scanning 28 intercostal spaces on antero-lateral chest, both at rest and at peak stress. Resting plasma B-type natriuretic peptide (BNP) levels and exercise capacity during cardiopulmonary testing with peak oxygen uptake (peak VO2 ) were assessed in all patients. All patients were followed up for a median of 8 months (first quartile, 6; third quartile, 11). LUS was feasible and interpretable in all subjects. The overall number of B-lines increased from rest (median 5, interquartile range 0-10) to peak stress (median 12, interquartile range 0-45) (P < 0.0001). The number of stress B-lines was closely correlated with resting log-BNP (r = 0.88, P < 0.0001) and peak VO2 (r = -0.90, P < 0.0001). During follow-up, 37 events occurred: 10 deaths, 23 re-hospitalizations for acute HF, and 4 non-fatal myocardial infarctions. Twelve-month event-free survival was 95% in the 36 patients with stress B-lines <30 (best cut-off identified by receiver operating characteristic curve analysis) vs. 7% in patients with ≥30 B-lines (P < 0.0001).Conclusion: B-lines are easy to obtain, frequent in HF patients, and often increase during ESE. Adverse events were more frequent in patients with more B-lines during ESE. [ABSTRACT FROM AUTHOR]

Aims Exercise stress echocardiography (ESE) is recommended by the European Society of Cardiology guidelines for the evaluation of heart failure (HF) patients. Recently, lung ultrasound (LUS) has been proposed for the assessment of extravascular lung water through B-lines. The aim of this study was to assess B-lines during ESE in HF. Methods and results Standard transthoracic and LUS evaluation was performed during semi-supine ESE in 103 NYHA class I-III HF patients (76 male; mean age 64±12 years) with depressed left ventricular ejection fraction (35±8%). B-lines were measured by scanning 28 intercostal spaces on antero-lateral chest, both at rest and at peak stress. Resting plasma B-type natriuretic peptide (BNP) levels and exercise capacity during cardiopulmonary testing with peak oxygen uptake (peak VO2) were assessed in all patients. All patients were followed up for a median of 8 months (first quartile, 6; third quartile, 11). LUS was feasible and interpretable in all subjects. The overall number of B-lines increased from rest (median 5, interquartile range 0-10) to peak stress (median 12, interquartile range 0-45) (P < 0.0001). The number of stress B-lines was closely correlated with resting log-BNP (r = 0.88, P < 0.0001) and peak VO2 (r = -0.90, P < 0.0001). During follow-up, 37 events occurred: 10 deaths, 23 re-hospitalizations for acute HF, and 4 non-fatal myocardial infarctions. Twelve-month event-free survival was 95% in the 36 patients with stress B-lines <30 (best cut-off identified by receiver operating characteristic curve analysis) vs. 7% in patients with ≥30 B-lines (P < 0.0001). Conclusion B-lines are easy to obtain, frequent in HF patients, and often increase during ESE. Adverse events were more frequent in patients with more B-lines during ESE. [ABSTRACT FROM AUTHOR]

The diffusion of smart-phones offers access to the best remote expertise in stress echo (SE). To evaluate the reliability of SE based on smart-phone filming and reading. A set of 20 SE video-clips were read in random sequence with a multiple choice six-answer test by ten readers from five different countries (Italy, Brazil, Serbia, Bulgaria, Russia) of the "SE2020" study network. The gold standard to assess accuracy was a core-lab expert reader in agreement with angiographic verification (0 = wrong, 1 = right). The same set of 20 SE studies were read, in random order and >2 months apart, on desktop Workstation and via smartphones by ten remote readers. Image quality was graded from 1 = poor but readable, to 3 = excellent. Kappa (k) statistics was used to assess intra- and inter-observer agreement. The image quality was comparable in desktop workstation vs. smartphone (2.0 ± 0.5 vs. 2.4 ± 0.7, p = NS). The average reading time per case was similar for desktop versus smartphone (90 ± 39 vs. 82 ± 54 s, p = NS). The overall diagnostic accuracy of the ten readers was similar for desktop workstation vs. smartphone (84 vs. 91%, p = NS). Intra-observer agreement (desktop vs. smartphone) was good (k = 0.81 ± 0.14). Inter-observer agreement was good and similar via desktop or smartphone (k = 0.69 vs. k = 0.72, p = NS). The diagnostic accuracy and consistency of SE reading among certified readers was high and similar via desktop workstation or via smartphone. [ABSTRACT FROM AUTHOR]

Aims Cardiac power output to left ventricular mass (power/mass) is an index of myocardial efficiency reflecting the rate at which cardiac work is delivered with respect to the potential energy stored in the left ventricular mass. In the present study, we sought to investigate the capability of power/mass assessed at peak of dobutamine stress echocardiography to predict mortality in patients with ischaemic cardiomyopathy and no inducible ischaemia. Methods and results One-hundred eleven patients (95 males; age 68 ± 10 years) with 35 ± 7% mean left ventricular ejection fraction and a dobutamine stress echocardiography (up to 40 mg/kg/min) negative by wall motion criteria formed the study population. Power/mass at peak stress was obtained as the product of a constant (K = 2.22 x 10-1) with cardiac output and the mean arterial pressure divided by left ventricular mass to convert the units to W/100 g. Patients were followed up for a median of 29 months (inter-quartile range 16-72 months). All-cause mortality was the only accepted clinical end point. Mean peak-stress power/mass was 0.70 ± 0.31 W/100 g. During follow-up, 29 deaths (26%) were registered. With a receiver operating characteristic analysis, a peak-stress power/mass ≤0.50 W/100 g [area under curve 0.72 (95% CI 0.63; 0.80), sensitivity 59%, specificity 80%] was the best value for predicting mortality. Univariate prognostic indicators were age, male sex, peak-stress ejection fraction, peak-stress stroke volume, peak-stress cardiac output, peak-stress cardiac power output ≤1.48 W, and peak-stress power/mass ≤0.50 W/100 g. At multivariate analysis, age (HR 1.08, 95% CI 1.04; 1.14; P = 0.004) and peak-stress power/mass ≤0.50 W/100 g (HR4.05,95% CI1.36; 12.00; P = 0.01) provided independent prognostic information. Three-year mortality was 14% in patients with peak-stress power/mass .0.50 W/100 g and 47% in those with peak-stress power/mass ≤0.50 W/100 g (log-rank 20.4; P < 0.0001). Conclusion Power/mass assessed at peak of dobutamine stress echocardiography allows effective prognostication in patients with ischaemic cardiomyopathy and test result negative by wall motion criteria. In particular, a peak-stress power/mass ≤50 W/100 g is a strong and multivariable predictor of mortality. [ABSTRACT FROM AUTHOR]

Background: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities.Methods: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy).Results: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios.Conclusions: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls. [ABSTRACT FROM AUTHOR]

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a “blind date” with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach. [ABSTRACT FROM AUTHOR]

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient. [ABSTRACT FROM AUTHOR]

Background: The effectiveness trial "Stress echo (SE) 2020" evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion.Purpose: To provide web-based upstream quality control and harmonization of B-lines reading criteria.Methods: 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics.Results: All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01).Conclusions: Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly. [ABSTRACT FROM AUTHOR]

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach. [ABSTRACT FROM AUTHOR]