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Background: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). Methods: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. Results: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015–4.680]; P =0.046) and ejection fraction P =0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). Conclusions: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 03049995.

Background: The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA). Objectives: The purpose of this study was to assess the feasibility and functional correlates of CFVR. Methods: This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. A subset of 1,867 patients was followed up. Results: The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome. Conclusions: CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome.

Background Left ventricular contractile reserve (LVCR), coronary flow velocity reserve (CFVR), and heart rate reserve (HRR) have recognized independent impact on outcome in heart failure (HF). They all can be simultaneously measured during dipyridamole stress echocardiography (DSE). Aim To assess the value of comprehensive DSE in patients with non-ischemic heart failure. Methods We evaluated 613 patients with HF, no history of coronary artery disease and no inducible regional wall motion abnormalities: 270 patients with preserved (≥50%) ejection fraction; 147 with mid-range (40–49%) ejection fraction; 196 with HF and reduced ( Results Abnormal CFVR, LVCR and HRR occurred in 29%, 44% and 46% of patients, respectively. After a median follow-up time of 20 months (interquartile range 12–32 months), 41 patients died. Annual mortality rate was lowest in patients (n=200) with normal response, and >10-fold higher in patients (n=96) with 3 abnormal criteria: see figure. At multivariable analysis, a reduced HRR (Hazard Ratio = 3.402, 95% Confidence Intervals 1.530–7.565, p=0.003) was the strongest SE independent predictor of all-cause death. Conclusion Abnormal LVCR, CFVR and HRR can be frequently observed during vasodilator SE in HF patients. They target different pathophysiological vulnerabilities (myocardial function, coronary microcirculation and cardiac autonomic system) and are useful for outcome prediction. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Consiglio nazionale delle ricerche - Institute of Clinical Physiology Figure 1

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years, ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) &lt, 1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve &lt, 1.85, 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610, 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579, 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

For the past 40 years, the methodology for stress echocardiography (SE) has remained basically unchanged. It is based on two-dimensional, black and white imaging, and is used to detect regional wall motion abnormalities (RWMA) in patients with known or suspected coronary artery disease (CAD). In the last five years much has changed and RWMA is not enough on its own to stratify patient risk and dictate therapy. Patients arriving at SE labs often have comorbidities and are undergoing full anti-ischemic therapy. The SE positivity rate based on RWMA fell from 70% in the eighties to 10% in the last decade. The understanding of CAD pathophysiology has shifted from a regional hydraulic disease to a systemic biologic disease. The conventional view of CAD encouraged the use of coronary anatomic imaging for diagnosis and the oculo-stenotic reflex for the deployment of therapy. This has led to a clinical oversimplification that ignores the lessons of pathophysiology and epidemiology, and in fact, CAD is not synonymous with ischemic heart disease. Patients with CAD may also have other vulnerabilities such as coronary plaque (step A of ABCDE-SE), alveolar-capillary membrane and pulmonary congestion (step B), preload and contractile reserve (step C), coronary microcirculation (step D) and cardiac autonomic balance (step E). The SE methodology based on two-dimensional echocardiography is now integrated with lung ultrasound (step B for B-lines), volumetric echocardiography (step C), color- and pulsed-wave Doppler (step D) and non-imaging electrocardiogram-based heart rate assessment (step E). In addition, qualitative assessment based on the naked eye has now become more quantitative, has been improved by contrast and based on cardiac strain and artificial intelligence. ABCDE-SE is now ready for large scale multicenter testing in the SE2030 study.

Background Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). Methods We enrolled 4,735 patients (age 63.6 ± 11.3 yrs, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (n=1,992 patients) and adenosine (n=18); ≤2.0 for exercise (n=2,087) or dobutamine (n=638). Results Force-based LVCR was obtained in all 4,735 pts. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57 % of patients with abnormal LVCR nevertheless showed increase in stroke volume. Conclusions Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Objectives The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE). Background B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE. Methods The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up. Results According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction. Conclusions Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020 - The International Stress Echo Study [SE2020]; NCT03049995)

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = −0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293–5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111–4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

Various lung ultrasound (LUS) scanning modalities have been proposed for the detection of B-lines, also referred to as ultrasound lung comets , which are an important indication of extravascular lung water at rest and after exercise stress echo (ESE). The aim of our study was to assess the lung water spatial distribution ( comet map ) at rest and after ESE. We performed LUS at rest and immediately after semi-supine ESE in 135 patients (45 women, 90 men; age 62 ± 12 y, resting left ventricular ejection fraction = 41 ± 13%) with known or suspected heart failure or coronary artery disease. B-lines were measured by scanning 28 intercostal spaces (ISs) on the antero-lateral chest, 2nd–5th IS, along with the midaxillary (MA), anterior axillary (AA), mid-clavicular (MC) and parasternal (PS) lines. Complete 28-region, 16-region (3rd and 4th IS), 8-region (3rd IS), 4-region (3rd IS, only AA and MA) and 1-region (left 3rd IS, MA) scans were analyzed. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. Interpretable images were obtained in all spaces (feasibility = 100 %). B-lines (>0 in at least 1 space) were present at ESE in 93 patients (69%) and absent in 42. More B-lines were found in the 3rd IS and along AA and MA lines. The B-line cumulative distribution was symmetric at rest (right/left = 1.10) and asymmetric with left lung predominance during stress (right/left = 0.67). The correlation of per-patient B-line number between 28-S and 16-S (R 2 = 0.9478), 8-S (R 2 = 0.9478) and 4-S scan (R 2 = 0.9146) was excellent, but only good with 1-S (R 2 = 0.8101). The average imaging and online analysis time were 5 s per space. In conclusion, during ESE, the comet map of lung water accumulation follows a predictable spatial pattern with wet spots preferentially aligned with the third IS and along the AA and MA lines. The time-saving 4-region scan is especially convenient during stress, simply dismissing dry regions and focusing on wet regions alone.

Background: Left ventricular contractile reserve (LVCR), coronary flow velocity reserve (CFVR), and heart rate reserve (HRR) affect outcome in heart failure (HF). They can be simultaneously measured during dipyridamole stress echocardiography (DSE). Aim: To assess the value of comprehensive DSE in patients with non-ischemic HF. Methods: We evaluated 610 patients with HF, no history of coronary artery disease, and no inducible regional wall motion abnormalities: 270 patients with preserved ejection fraction (≥50%), 146 patients with mid-range ejection fraction (40–49%), and 194 patients with reduced ejection fraction (&lt, 40%). All underwent DSE (0.84 mg/kg in 6’) in 7 accredited laboratories. We measured LVCR (abnormal value ≤ 1.1), CFVR in left anterior descending artery (abnormal value: ≤2.0), and HRR (peak/rest heart rate, abnormal value: ≤1.22). All patients were followed up. Results: Abnormal CFVR, LVCR, and HRR occurred in 29%, 45%, and 47% of patients, respectively (p &lt, 0.001). After a median follow-up time of 20 months (interquartile range: 12–32 months), 113 hard events occurred in 105 patients with 41 deaths, 8 myocardial infarctions, 61 admissions for acute HF, and 3 strokes. The annual mortality rates were 0.8% in 200 patients with none abnormal criteria, 1.8% in 184 patients with 1 abnormal criterion, 7.1% in 130 patients with 2 abnormal criteria, 7.5% in 96 patients with 3 abnormal criteria. Conclusion: Abnormal LVCR, CFVR, and HRR were frequent during DSE in non-ischemic HF patients. They target different pathophysiological vulnerabilities (myocardial function, coronary microcirculation, and cardiac autonomic balance) and are useful for outcome prediction.

Background: The trial "Stress Echo (SE) 2020" evaluates novel applications of SE beyond coronary artery disease. The aim of the study was control quality and harmonize reading criteria.Methods: One reader from 78 centers of the SE 2020 network asked for credentials to read a set of 20 SE videoclips selected by the core lab. All aspiring centers met the pre-requisite of high-volume and the years of experience in SE ranged from 5 to 31 years (mean value 18 years). The diagnostic gold standard was a reading by the core lab. The a priori determined pass threshold was 18/20 (>= 90%).Results: Of the initial 78 who started, 57 completed the first attempt: individual readers' score on first attempt ranged from 07/20 to 20/20 (accuracy from 35% to 100%, mean 78.7 +/- 13%) and 44 readers passed it. There was a very poor correlation between years of experience and the reader's score on first attempt (r = -0.161, p = 0.231). Of the 13 readers who failed the first attempt, 12 took it again after the web-based session and their accuracy improved (74% vs. 96%, p < 0.001). The kappa inter-observer agreement before and after web-based training was 0.59 on first attempt and rose to 0.91 on the last attempt.Conclusions: In SE reading, the volume of activity or years of experience is not synonymous with diagnostic quality. Qualitative analysis and operator-dependence can become a limiting weakness in clinical practice, in the absence of strict pathways of learning, credentialing and audit. (C) 2017 Elsevier B.V. All rights reserved.

INTRODUÇÃO: Novas abordagens terapêuticas que objetivam melhorar a sensação de dispneia e fadiga em pacientes com insuficiência cardíaca, como a aplicação de pressão positiva expiratória nas vias aéreas (EPAP), podem ser aplicadas na tentativa de melhorar a capacidade funcional e a qualidade de vida. OBJETIVO: Avaliar os efeitos da utilização da EPAP ( Expiratory Positive Airway Pressure) durante o esforço em indivíduos portadores de IC classe funcional II e III (NYHA). MÉTODOS: Dos 390 pacientes, foram selecionados 28 com FEVE < 40%. O Teste de Caminhada de seis minutos (TC6') foi realizado três vezes: o primeiro para a familiarização, um com a máscara e o outro sem a máscara de EPAP, sendo válido os dois últimos. A comparação entre os dados obtidos foi realizada por meio de teste t de Student pareado ou teste de Wilcoxon, conforme a normalidade dos dados. RESULTADOS: a percepção de esforço foi maior após a caminhada com a utilização da máscara quando comparado na ausência da máscara. Houve elevação significativa na saturação de oxigênio quando os pacientes estavam usando a máscara de EPAP. CONCLUSÃO: O uso da máscara de EPAP aumenta a percepção de esforço e o trabalho ventilatório, porém, não aumentou a distância percorrida no TC6, sendo sua aplicabilidade questionável em programas de reabilitação cardiovascular.INTRODUCTION: New therapeutic approaches that aim to improve the sensation of dyspnea and fatigue in patients with heart failure, as the application of positive pressure airway expiratory (EPAP) Expiratory Positive Airway Pressure should be tested in an attempt to improve functional capacity and quality of life. OBJECTIVE: To evaluate the effects of the use of EPAP during exercise in patients with heart failure functional class II and III (NYHA). METHODS: Of 390 patients, 28 were selected with LVEF

INTRODUÇÃO: Novas abordagens terapêuticas que objetivam melhorar a sensação de dispneia e fadiga em pacientes com insuficiência cardíaca, como a aplicação de pressão positiva expiratória nas vias aéreas (EPAP), podem ser aplicadas na tentativa de melhorar a capacidade funcional e a qualidade de vida. OBJETIVO: Avaliar os efeitos da utilização da EPAP ( Expiratory Positive Airway Pressure) durante o esforço em indivíduos portadores de IC classe funcional II e III (NYHA). MÉTODOS: Dos 390 pacientes, foram selecionados 28 com FEVE < 40%. O Teste de Caminhada de seis minutos (TC6') foi realizado três vezes: o primeiro para a familiarização, um com a máscara e o outro sem a máscara de EPAP, sendo válido os dois últimos. A comparação entre os dados obtidos foi realizada por meio de teste t de Student pareado ou teste de Wilcoxon, conforme a normalidade dos dados. RESULTADOS: a percepção de esforço foi maior após a caminhada com a utilização da máscara quando comparado na ausência da máscara. Houve elevação significativa na saturação de oxigênio quando os pacientes estavam usando a máscara de EPAP. CONCLUSÃO: O uso da máscara de EPAP aumenta a percepção de esforço e o trabalho ventilatório, porém, não aumentou a distância percorrida no TC6, sendo sua aplicabilidade questionável em programas de reabilitação cardiovascular. INTRODUCTION: New therapeutic approaches that aim to improve the sensation of dyspnea and fatigue in patients with heart failure, as the application of positive pressure airway expiratory (EPAP) Expiratory Positive Airway Pressure should be tested in an attempt to improve functional capacity and quality of life. OBJECTIVE: To evaluate the effects of the use of EPAP during exercise in patients with heart failure functional class II and III (NYHA). METHODS: Of 390 patients, 28 were selected with LVEF