Rigo, Fausto

Abstract Aims Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. The aim of the study is to assess the risk stratification value of CI during exercise or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods and results In a prospective, multicenter, international, observational study, we enrolled 13 445 patients with known or suspected chronic coronary syndromes who underwent stress echocardiography in 19 clinical sites from 10 countries using either exercise (n = 2594), dobutamine (n = 2440), or dipyridamole (n = 8411). Heart rate was automatically measured from the 1-lead ECG in the echocardiography monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) ≤ 1.22 (≤1.17 if in permanent atrial fibrillation) for dipyridamole stress. The primary outcome was all-cause death. CI was observed in 5045 patients (38%) and stress-induced regional wall motion abnormalities in 1648 (13%). Over a median follow-up time of 3.4 years (interquartile range, 1.6–9.1 years), there were 2426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (P < 0.0001). CI was associated with a significant increase in 10-year mortality in all age groups ranging from ≤54 years to ≥75 years (P < 0.0001). In addition, it was associated with increased mortality (P < 0.0001) irrespective of β-blocker use. Cox multivariable analysis revealed that CI was an independent predictor of mortality (HR: 1.60, 95% confidence interval: 1.47–1.74; P < 0.0001) together with age, male sex, diabetes mellitus, left ventricular ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during exercise or pharmacological stress is a simple and objective predictor of survival.

Over the past decade, stress echocardiography has evolved from a test for assessing epicardial artery stenosis to a comprehensive functional test, targeting multiple cardiovascular parameters. The new approach includes several structured steps: (a) evaluating regional wall motion abnormalities to detect epicardial artery stenosis or vasospasm; (b) assessing pulmonary congestion and diastolic function via B-lines with lung ultrasound; (c) gauging preload and contractile reserve with volumetric echocardiography; (d) measuring coronary microvascular reserve using Doppler-based coronary flow velocity in the middistal left anterior descending artery; and (e) determining cardiac sympathetic reserve by tracking heart rate reserve on an ECG. This evolution was supported extensively by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), which played a key role in five areas: (1) developing the initial, curiosity-driven project; (2) disseminating protocols and results at national and international conferences, supporting logistic infrastructure and publication expenses; (3) establishing a digital platform (customized Redcap) for data entry and storage; (4) facilitating patient recruitment across 19 Italian centers; and (5) offering formal endorsement through six presidencies, adding credibility and reach beyond any single institution. The protocol quickly advanced from concept to high-impact publications, earning inclusion in 2024 specialty guidelines. Initially Italian-led, the study now includes 50 centers across 20 countries (e.g. USA and China). Beyond the 50 peer-reviewed papers published in 2016–2024, this study offers a novel, sustainable approach to cardiac stress testing, providing more information at lower costs, with zero radiation and minimal environmental impact. SIECVI’s endorsement was instrumental in amplifying the study’s rigor and outreach.

Abstract Background Cardiovascular abnormalities have been observed in half of all COVID-19 patients in the acute phase of the infection. Additionally, 10-35% of these patients have various long-term symptoms diagnosed with post-acute sequelae of COVID-19 (PASC). Aim of this study was to evaluate the role of exercise stress echocardiography (ESE) with an integrated approach, inclusive of Speckle-Tracking Echocardiography (STE) with Myocardial Work (MW) analysis in the evaluation of patients after COVID infection. Methods We prospectively recruited a population of 370 post-COVID 19 patients (Group 1) (225 males; 55.8 ±8.3 years), and of 250 age- and sex-comparable healthy controls (Group 2). In Standard Doppler echocardiography, STE and MW analyses and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Results Left ventricular (LV) wall thickness, diameters and mass index were comparable between the two groups. Both LV ejection fraction (EF) and right ventricular (RV) functional indexes (TAPSE and Tissue Doppler S’ wave) at rest did not show differences between the two groups. Conversely, baseline LV GLS (-16.2±2.8 vs. –20.4±3.3 %; p<0.01), MW efficiency (88.8±3.2 vs. 93.2±3.3 %; p<0.001), and RV strain (-16.4±2.8 vs. –20.4±4.3 %; p<0.01), were significantly reduced in Group 1. Also pulmonary artery systolic pressures (PASP) (33.5±3.8 vs. 24.6±3.1 mmHg; p<0.001), and LV E/e’ ratio were significantly increased in COVID group, while B-lines ( ≥ 2) at rest were found in 25.3% of Group 1 and 5.1% of Group 2 (p < 0.001). During effort, COVID patients showed reduced exercise time and exercise capacity (<0.001). Values of LVEF, RV strain and LV GLS (all with p value <0.01) and MWE (p<0001) were much lower in COVID patients when compared to Group 2. Additionally, COVID patients showed at peak effort an increased LV E/e’ ratio, pulmonary pressures and B-lines by lung ultrasound (all p <0.001). Multivariable analysis detected independent associations of baseline GLS and MWE with maximal workload (watts reached), LV E/e’ ratio and B-lines during effort (p<0.001), stronger than the association of LVEF with the same functional parameters (p<0.01). What’s more, RV strain (p<0.001) was significantly associated with PASP levels at peak effort. Conclusions In post-COVID patients, biventricular involvement with impairment of LV and RV systolic function is frequent, missed by conventional indices such as EF or TAPSE, and detected by more sensitive STE indices such as LV-GLS, ME, and RV-strain. These alterations are functionally significant and associated with shorter exercise -time, more pulmonary hypertension, and greater pulmonary congestion during stress.

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 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

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 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.