Since the 2009 publication of the stress echocardiography expert consensus of the European Association of Echocardiography, and after the 2016 advice of the American Society of Echocardiography-European Association of Cardiovascular Imaging for applications beyond coronary artery disease, new information has become available regarding stress echo. Until recently, the assessment of regional wall motion abnormality was the only universally practiced step of stress echo. In the state-of-the-art ABCDE protocol, regional wall motion abnormality remains the main step A, but at the same time, regional perfusion using ultrasound-contrast agents may be assessed. Diastolic function and pulmonary B-lines are assessed in step B; left ventricular contractile and preload reserve with volumetric echocardiography in step C; Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and ECG-based heart rate reserve in non-imaging step E. These five biomarkers converge, conceptually and methodologically, in the ABCDE protocol allowing comprehensive risk stratification of the vulnerable patient with chronic coronary syndromes. The present document summarizes current practice guidelines recommendations and training requirements and harmonizes the clinical guidelines of the European Society of Cardiology in many diverse cardiac conditions, from chronic coronary syndromes to valvular heart disease. The continuous refinement of imaging technology and the diffusion of ultrasound-contrast agents improve image quality, feasibility, and reader accuracy in assessing wall motion and perfusion, left ventricular volumes, and coronary flow velocity. Carotid imaging detects pre-obstructive atherosclerosis and improves risk prediction similarly to coronary atherosclerosis. The revolutionary impact of artificial intelligence on echocardiographic image acquisition and analysis makes stress echo more operator-independent and objective. Stress echo has unique features of low cost, versatility, and universal availability. It does not need ionizing radiation exposure and has near-zero carbon dioxide emissions. Stress echo is a convenient and sustainable choice for functional testing within and beyond coronary artery disease.

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. 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 < 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. ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes. This study recruited 3,574 patients from 13 stress echo laboratories of 5 countries and shows the prognostic value of the new state-of-the art cardiac functional testing with stress echo ABCDE protocol: Step A for regional wall motion abnormalities; step B for B-lines obtained with 4-site simplified scan and lung ultrasound; step C for contractile reserve with volumetric echocardiography; step D for Doppler-based assessment of coronary flow reserve in mid-distal left anterior descending coronary artery; step E for EKG-based heart rate reserve.

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. 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). 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. 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.

Background: The pericoronary fat attenuation index ( pFAI ) has emerged as a marker of coronary inflammation, which is measurable from standard coronary computed tomography angiography ( CCTA ). It compares well with gold‐standard methods for the assessment of coronary inflammation and can predict future cardiovascular events. pFAI could prove invaluable to differentiate an inflammatory from a noninflammatory coronary artery status, helping unravel the mechanisms subtending an event classified as myocardial infarction with nonobstructive coronary arteries ( MINOCA ) or Tako‐Tsubo syndrome ( TTS ). Methods and Results: Patients admitted with MINOCA and TTS between 2011 and 2018, who had both CCTA and cardiac magnetic resonance during or shortly after the acute phase, were selected and pFAI measured in their CCTA ; pFAI was also measured in control subjects who had CCTA for atypical chest pain workup, no obstructive coronary artery disease found in their CCTA, and no cardiac events at 2‐year follow‐up. In the n=106 MINOCA / TT S patients, mean pFAI was −68.37±8.29 versus −78.03±6.20 in the n=106 controls ( P <0.0001), and the difference was confirmed also when comparing mean pFAI in each coronary artery between MINOCA / TT S and controls ( P <0.0001). Nonobstructive coronary plaques at CCTA , high‐risk plaques in particular, were more frequently found ( P <0.01) in the MINOCA / TT S group compared with controls. Conclusions: In MINOCA and TT S patients, CCTA is not only able to detect angiographically invisible atherosclerotic plaques, but its diagnostic yield can be expanded using the simple measurement of pFAI to characterize pericoronary fat tissue; in MINOCA / TT S mean pFAI demonstrates higher values compared with controls, a finding that has been associated with coronary artery inflammation.

Background—: The addition of myocardial perfusion (MP) imaging during dipyridamole real-time contrast echocardiography improves the sensitivity to detect coronary artery disease, but its prognostic value to predict hard cardiac events in large numbers of patients with known or suspected coronary artery disease remains unknown. Methods and Results—: We studied 1252 patients with the use of dipyridamole real-time contrast echocardiography and followed them for a median of 25 months. The prognostic value of MP imaging regarding death and nonfatal myocardial infarction was determined and related to wall motion (WM), clinical risk factors, and rest ejection fraction by the use of Cox proportional-hazards models, C index, and risk reclassification analysis. A total of 59 hard events (4.7%) occurred during the follow-up (24 deaths, 35 myocardial infarctions). The 2-year event-free survival was 97.9% in patients with normal MP and WM, 91.9% with isolated reversible MP defects but normal WM, and 67.4% with both reversible MP and WM abnormalities ( P <0.001). By multivariate analysis the independent predictors of events were age (hazard ratio 1.05, 95% confidence interval [CI], 1.02–1.08), sex (hazard ratio, 2.36; 95% CI, 1.32–4.23), reversible MP defects (hazard ratio, 3.88; 95% CI, 1.83–8.21), and reversible WM abnormalities with reversible MP defects (hazard ratio, 4.51; 95% CI, 2.25–9.07). Reversible MP defects added incremental predictive value and reclassification benefit over WM response and clinical factors ( P =0.001). Conclusions—: MP imaging using real-time perfusion echocardiography during dipyridamole real-time contrast echocardiography provides independent, incremental prognostic information regarding hard cardiac events in patients with known or suspected coronary artery disease. Patients with normal MP responses have better outcome than patients with normal WM; patients with both reversible WM and MP abnormalities have the worst outcome.