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Background: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. Aim: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. Methods: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. Results: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). Conclusions: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Abstract Functional testing with stress echocardiography is based on the detection of regional wall motion abnormality with two-dimensional echocardiography and is embedded in clinical guidelines. Yet, it under-uses the unique versatility of the technique, ideally suited to describe the different functional abnormalities underlying the same wall motion response during stress. Five parameters converge conceptually and methodologically in the state-of-the-art ABCDE protocol, assessing multiple vulnerabilities of the ischemic patient. The five steps of the ABCDE protocol are (1) step A: regional wall motion; (2) step B: B-lines by lung ultrasound assessing extravascular lung water; (3) step C: left ventricular contractile reserve by volumetric two-dimensional echocardiography; (4) step D: coronary flow velocity reserve in mid-distal left anterior descending coronary with pulsed-wave Doppler; and (5) step E: assessment of heart rate reserve with a one-lead electrocardiogram. ABCDE stress echo offers insight into five functional reserves: epicardial flow (A); diastolic (B), contractile (C), coronary microcirculatory (D), and chronotropic reserve (E). The new format is more comprehensive and allows better functional characterization, risk stratification, and personalized tailoring of therapy. ABCDE protocol is an ‘ecumenic’ and ‘omnivorous’ functional test, suitable for all stresses and all patients also beyond coronary artery disease. It fits the need for sustainability of the current era in healthcare, since it requires universally available technology, and is low-cost, radiation-free, and nearly carbon-neutral.

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 <50% (hazard ratio, 2.942 [95% CI, 1.268–6.822]; 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.

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf Stress Echo 2020 study group of the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) Background The classical pathophysiological cornerstone of stress cardiac imaging is the ischemic cascade: alterations in coronary flow velocity reserve (CFVR) come first, regional wall motion abnormalities (RWMA) second, and global alterations of left ventricular diastolic and systolic function last. Aim To evaluate the ischemic cascade with stress echo (SE) assessed with ABCDE protocol. Methods We analyzed 1616 patients (age 66 ± 10 years, 1156, 72% males) with chest pain and angiographically documented coronary artery disease (CAD): 928 (57.4%) with previous myocardial infarction and 1451 (89.8%) with previous coronary revascularization. CAD patients were studied with ABCDE-SE protocol by 13 certified laboratories of 5 countries. Stress modality was exercise in 427 (26.4%) dobutamine in 173 (10.7%) and vasodilator stress in 1016 (62.9%) patients (dipyridamole in 982 – 60.8% and adenosine in 34 – 2.1% patients). Step A assessed RWMA; step B, B-lines (diastolic function); step C, left ventricular contractile reserve based on force; step D, CFVR in left anterior descending artery; step E, heart rate reserve. SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). Follow up was obtained in all patients. Results Results were abnormal in 350 (21.7) % for step A, 572 (35.4%) for B, 666 (41.2%) for C, 546 (33.5%) for D and 643 (39.8%) for E. The distribution of positivity is shown in figure. The dominant "solitary phenotype" (only one biomarker abnormal during the test) was step A in 10 (0.6%), step B in 124 (7.7%) step C in 100 (6.2%), step D in 64 (4.0%) and step E in 157 (9.7%) patients. The overall sensitivity for CAD detection including each step of ABCDE score (≥1) was 95.7%. During median follow-up of 22 months [IQ range: 13-37 months] 279 coronary revascularizations occurred. ABCDE score predicted coronary revascularization with score 1: HR: 3.182, 95% CI: 1.699-6.067; score 2: HR: 4.921, 95% CI: 2.571-9.420; score 3: HR: 7.234, 95% CI: 3.743-13.979; score 4: HR: 24.570, 95% CI: 13.390-45.086; and score 5: HR: 38.720, 95% CI: 20.975-71.478 Conclusion Inducible ischemia with CAD is characterized by the complexity and multiplicity of diagnostic phenotypes. The overall ABCDE score predicts clinically driven revascularization. Abstract Figure. The 5 circles of ischemia biomarkers

Abstract Background Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B-lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, EKG-based heart rate reserve. Aim: to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicenter, international, effectiveness study. Methods From July 2016 to November 2020, we enrolled 3,574 all-comers (age 65±11 years, 2,070 males, 58%; ejection fraction 60±10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent ABCDE-SE. The employed stress modality was exercise (n=952, with semi-supine bike, n=887, or treadmill, n=65 with adenosine for step D) or pharmacological stress (n=2,622, with vasodilator, n=2,151; or dobutamine, n=471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only end-point. Results Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D and 37% for E step. During a median follow-up of 21 months, 73 deaths occurred. At univariable analysis, predictors of all-cause mortality were step B (hazard ratio, HR: 2.621, 95% Confidence Intervals, CI: 1.654–4.152, p&lt;0.001), step D (HR: 2.578, 95% CI: 1.624–4.093, p&lt;0.001), and step E (HR: 2.955, 95% CI: 1.848–4.725, p&lt;0.001), but not step A (HR: 1.333, 95% CI: 0.731–2.430, p=0.349) and step C (HR1.581, 95% CI: 0.997–2.506, p=0.051). At multivariable analysis, ABCDE-SE was an independent predictor of mortality with score 3 (HR: 3.472, 95% CI: 1.483–8.135, p=0.004), 4 (HR: 4.045, 95% CI: 1.595–10.259, p=0.003) and 5 (HR: 5.678, 95% CI: 2.106–15.313, p=0.001) (Figure). Annual mortality rate ranged from 0.4% person/year for score 0 up to 2.4% person/year for score 5. Conclusion ABCDE-SE allows an effective risk stratification of patient global vulnerability. Funding Acknowledgement Type of funding sources: None. Survival curves based on ABCDE score

Abstract Aim The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. Methods and results From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13–36), 73 deaths occurred. Global X 2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B–E steps (P &lt; 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. Conclusion ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the “ABCDE protocol” of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study.

Abstract A unique and highly versatile technique, stress echocardiography (SE) is increasingly recognized for its utility in the evaluation of non-ischaemic heart disease. SE allows for simultaneous assessment of myocardial function and haemodynamics under physiological or pharmacological conditions. Due to its diagnostic and prognostic value, SE has become widely implemented to assess various conditions other than ischaemic heart disease. It has thus become essential to establish guidance for its applications and performance in the area of non-ischaemic heart disease. This paper summarizes these recommendations.